This case report investigates the manifestation of cerebral amyloid angiopathy (CAA) through recurrent Transient Ischemic Attacks (TIAs) in an 82-year-old patient. Despite initial diagnostic complexities, cerebral ang...This case report investigates the manifestation of cerebral amyloid angiopathy (CAA) through recurrent Transient Ischemic Attacks (TIAs) in an 82-year-old patient. Despite initial diagnostic complexities, cerebral angiography-MRI revealed features indicative of CAA. Symptomatic treatment resulted in improvement, but the patient later developed a fatal hematoma. The discussion navigates the intricate therapeutic landscape of repetitive TIAs in the elderly with cardiovascular risk factors, emphasizing the pivotal role of cerebral MRI and meticulous bleeding risk management. The conclusion stresses the importance of incorporating SWI sequences, specifically when suspecting a cardioembolic TIA, as a diagnostic measure to explore and exclude CAA in the differential diagnosis. This case report provides valuable insights into these challenges, highlighting the need to consider CAA in relevant cases.展开更多
β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unkno...β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.展开更多
In the central nervous system, the formation of fibrotic scar after injury inhibits axon regeneration and promotes repair. However, the mechanism underlying fibrotic scar formation and regulation remains poorly unders...In the central nervous system, the formation of fibrotic scar after injury inhibits axon regeneration and promotes repair. However, the mechanism underlying fibrotic scar formation and regulation remains poorly understood. M2 macrophages regulate fibrotic scar formation after injury to the heart, lung, kidney, and central nervous system. However, it remains to be clarified whether and how M2 macrophages regulate fibrotic scar formation after cerebral ischemia injury. In this study, we found that, in a rat model of cerebral ischemia induced by middle cerebral artery occlusion/reperfusion, fibrosis and macrophage infiltration were apparent in the ischemic core in the early stage of injury(within 14 days of injury). The number of infiltrated macrophages was positively correlated with fibronectin expression. Depletion of circulating monocyte-derived macrophages attenuated fibrotic scar formation. Interleukin 4(IL4) expression was strongly enhanced in the ischemic cerebral tissues, and IL4-induced M2 macrophage polarization promoted fibrotic scar formation in the ischemic core. In addition, macrophage-conditioned medium directly promoted fibroblast proliferation and the production of extracellular matrix proteins in vitro. Further pharmacological and genetic analyses showed that sonic hedgehog secreted by M2 macrophages promoted fibrogenesis in vitro and in vivo, and that this process was mediated by secretion of the key fibrosis-associated regulatory proteins transforming growth factor beta 1 and matrix metalloproteinase 9. Furthermore, IL4-afforded functional restoration on angiogenesis, cell apoptosis, and infarct volume in the ischemic core of cerebral ischemia rats were markedly impaired by treatment with an sonic hedgehog signaling inhibitor, paralleling the extent of fibrosis. Taken together, our findings show that IL4/sonic hedgehog/transforming growth factor beta 1 signaling targeting macrophages regulates the formation of fibrotic scar and is a potential therapeutic target for ischemic stroke.展开更多
In vivo imaging of cerebral ischemia/reperfusion injury remains an important challenge.We injected porous Ag/Au@SiO_(2) bimetallic hollow nanoshells carrying anti-tropomyosin 4 as a molecular probe into mice with cere...In vivo imaging of cerebral ischemia/reperfusion injury remains an important challenge.We injected porous Ag/Au@SiO_(2) bimetallic hollow nanoshells carrying anti-tropomyosin 4 as a molecular probe into mice with cerebral ischemia/reperfusion injury and observed microvascular changes in the brain using photoacoustic imaging with ultrasonography.At each measured time point,the total photoacoustic signal was significantly higher on the affected side than on the healthy side.Twelve hours after reperfusion,cerebral perfusion on the affected side increased,cerebrovascular injury worsened,and anti-tropomyosin 4 expression increased.Twenty-four hours after reperfusion and later,perfusion on the affected side declined slowly and stabilized after 1 week;brain injury was also alleviated.Histopathological and immunohistochemical examinations confirmed the brain injury tissue changes.The nanoshell molecular probe carrying anti-tropomyosin 4 has potential for use in early diagnosis of cerebral ischemia/reperfusion injury and evaluating its progression.展开更多
Neuroprotection by ischemic preconditioning has been confirmed by many studies, but the precise mechanism remains unclear. In the present study, we performed cerebral ischemic pre- conditioning in rats by simulating a...Neuroprotection by ischemic preconditioning has been confirmed by many studies, but the precise mechanism remains unclear. In the present study, we performed cerebral ischemic pre- conditioning in rats by simulating a transient ischemic attack twice (each a 20-minute occlusion of the middle cerebral artery) before inducing focal cerebral infarction (2 hour occlusion-reper- fusion in the same artery). We also explored the mechanism underlying the neuroprotective effect of ischemic preconditioning. Seven days after ocdusion-reperfusion, tetrazolium chloride staining and immunohistochemistry revealed that the infarct volume was significantly smaller in the group that underwent preconditioning than in the model group. Furthermore, vascular endothelial growth factor immunoreactivity was considerably greater in the hippocampal CA3 region of preconditioned rats than model rats. Our results suggest that the protective effects of ischemic preconditioning on focal cerebral infarction are associated with upregulation of vascu- lar endothelial growth factor.展开更多
Ischemic stroke(IS) is a disease caused by deficiency of blood and oxygen in focal or complete brain,followed by inflammation cascade and other pathological reactions,which finally lead to irreversible damage to the c...Ischemic stroke(IS) is a disease caused by deficiency of blood and oxygen in focal or complete brain,followed by inflammation cascade and other pathological reactions,which finally lead to irreversible damage to the cerebrum.For the inflammation is a key progress at the initiation of ischemia and poststroke,and chemokines work as vital cytokines in inflammation,we focus the roles of chemokines in IS.Studies have shown cerebral ischemia is associated with marked induction of both CXC and CC chemokines which resulting in extensive leukocyte infiltration in the ischemic brain,and neutrophil infiltration may increase cerebral edema inducing injury in the ischemic area.In addition,chemokines also shows other functions such as promote neuroblast migration,hematogenous cell recruitment and functional brain repair.Thus,a similar chemokine ligand/chemokine receptor pair can mediate both beneficial and detrimental effects depending on the window of observation and pathophysiological conditions.This manuscript reviews the studies about chemokine-mediated effects in cerebral ischemia/reperfusion and discusses the potential significance of these interactions in injury and repair of ischemic tissues.We also refer drug development based on the chemokines and clinical applications using chemokines as diagnostic or prognostic biomarkers in ischemic stroke.展开更多
It is difficult to control the degree of ischemic postconditioning in the brain and other isch- emia-sensitive organs. Remote ischemic postconditioning could protect some ischemia-sensitive organs through measures on ...It is difficult to control the degree of ischemic postconditioning in the brain and other isch- emia-sensitive organs. Remote ischemic postconditioning could protect some ischemia-sensitive organs through measures on terminal organs. In this study, a focal cerebral ischemia-reperftlsion injury model was established using three cycles of remote ischernic postconditioning, each cycle consisted of 10-minute occlusion of the femoral artery and 10-minute opening. The results showed that, remote ischemic postconditioning significantly decreased the percentage of the in- farct area and attenuated brain edema. In addition, inflammatory nuclear factor-KB expression was significantly lower, while anti-apoptotic Bcl-2 expression was significantly elevated in the ce- rebral cortex on the ischemic side. Our findings indicate that remote ischemic postconditioning attenuates focal cerebral ischemia/reperfusion injury, and that the neuroprotective mechanism is mediated by an anti-apoptotic effect and reduction of the inflammatory response.展开更多
To investigate the effects of mRNA interference on aquaporin-4 expression in swollen tissue of rats with ischemic cerebral edema, and diagnose the significance of diffusion-weighted MRI, we injected 5 pL shRNA- aquapo...To investigate the effects of mRNA interference on aquaporin-4 expression in swollen tissue of rats with ischemic cerebral edema, and diagnose the significance of diffusion-weighted MRI, we injected 5 pL shRNA- aquaporin-4 (control group) or siRNA- aquaporin-4 solution (1:800) (RNA interference group) into the rat right basal ganglia immediately before occlusion of the middle cerebral artery. At 0.25 hours after occlusion of the middle cerebral artery, diffusion-weighted MRI displayed a high signal; within 2 hours, the relative apparent diffusion coefficient decreased markedly, aquaporin-4 expression increased rapidly, and intracellular edema was obviously aggravated; at 4 and 6 hours, the relative apparent diffusion coefficient slowly returned to control levels, aquaporin-4 expression slightly increased, and angioedema was observed. In the RNA interference group, during 0.25- 6 hours after injection of siRNA- aquaporin-4 solution, the relative apparent diffusion coefficient slightly fluctuated and aquaporin-4 expression was upregulated; during 0.5 4 hours, the relative apparent diffusion coefficient was significantly higher, while aquaporin-4 expression was significantly lower when compared with the control group, and intracellular edema was markedly reduced; at 0.25 and 6 hours, the relative apparent diffusion coefficient and aquaporin-4 expression were similar when compared with the control group; obvious angioedema remained at 6 hours. Pearson's correlation test results showed that aquaporin-4 expression was negatively correlated with the apparent diffusion coefficient (r = -0.806, P 〈 0.01). These findings suggest that upregulated aquaporin-4 expression is likely to be the main molecular mechanism of intracellular edema and may be the molecular basis for decreased relative apparent diffusion coefficient. Aquaporin-4 gene interference can effectively inhibit the upregulation of aquaporin-4 expression during the stage of intracelfular edema with time-effectiveness. Moreover, diffusion-weighted MRI can accurately detect intracellular edema.展开更多
MicroRNAs are a family of small, genome-encoded endogenous RNAs that are transcribed but are not translated into proteins. They serve essential roles in virtually every aspect of brain function, including neurogenesis...MicroRNAs are a family of small, genome-encoded endogenous RNAs that are transcribed but are not translated into proteins. They serve essential roles in virtually every aspect of brain function, including neurogenesis, neural development, and cellular responses leading to changes in synaptic plasticity. They are also implicated in neurodegeneration and neurological disorders, in responses to hypoxia and ischemia, and in ischemic tolerance induced by ischemic preconditioning. In recent developments, miRNA expres- sion profiling has been examined in stroke, and these studies indicate that miRNAs have emerged as key mediators in ischemic stroke biology. Both increased and decreased miRNA levels may be needed either as prevention or treatment of stroke. Novel approaches are being developed to get miRNA related therapeu- tics into the brain across an intact blood-brain barrier, including chemical modification, use of targeting molecules and methods to disrupt the blood-brain barrier.展开更多
Recently,we have reported that Oenanthe javanica extract(OJE)displays strong neuroprotective effect against ischemic damage after transient global cerebral ischemia.However,neuroprotective mechanisms of OJE have not b...Recently,we have reported that Oenanthe javanica extract(OJE)displays strong neuroprotective effect against ischemic damage after transient global cerebral ischemia.However,neuroprotective mechanisms of OJE have not been fully identified.Thus,this study investigated the neuroprotection of OJE in the hippocampal CA1 area and its anti-inflammatory activity in gerbils subjected to 5 minutes of transient global cerebral ischemia.We treated the animals by intragastrical injection of OJE(100 and 200 mg/kg)once daily for 1 week prior to transient global cerebral ischemia.Neuroprotection of OJE was observed by immunohistochemistry for neuronal nuclear antigen and histofluorescence staining for Fluoro-Jade B.Immunohistochemistry of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 was done for astrocytosis and microgliosis,respectively.To investigate the neuroprotective mechanisms of OJE,we performed immunohistochemistry of tumor necrosis factor-alpha and interleukin-2 for pro-inflammatory function and interleukin-4 and interleukin-13 for anti-inflammatory function.When we treated the animals by intragastrical administration of 200 mg/kg of OJE,hippocampal CA1 pyramidal neurons were protected from transient global cerebral ischemia and cerebral ischemia-induced gliosis was inhibited in the ischemic hippocampal CA1 area.We also found that interleukin-4 and-13 immunoreactivities were significantly increased in pyramidal neurons of the ischemic CA1 area after OJE pretreatment,and the increased immunoreactivities were sustained in the CA1 pyramidal neurons after transient global cerebral ischemia.However,OJE pretreatment did not increase interleukin-2 and tumor necrosis factor-alpha immunoreactivities in the CA1 pyramidal neurons.Our findings suggest that pretreatment with OJE can protect neurons and attenuate gliosis from transient global cerebral ischemia via increasing expressions of interleukin-4 and-13.The experimental plan of this study was reviewed and approved by the Institutional Animal Care and Use Committee(IACUC)in Kangwon National University(approval No.KW-160802-1)on August 10,2016.展开更多
The astrocyte is a critical regulator of neuronal survival after ischemic brain injury. Electroacupuncture may be an effective therapy for cerebral ischemia, as electroacupuncture frequency can affect the structural i...The astrocyte is a critical regulator of neuronal survival after ischemic brain injury. Electroacupuncture may be an effective therapy for cerebral ischemia, as electroacupuncture frequency can affect the structural integdty of astrocytes. In this study, a rat model of middle cerebral artery occlusion established using the modified thread embolism method was treated with electroacupuncture of the bilateral Quchi (Llll) and Zusanfi (ST36) at 15, 30, and 100 Hz frequencies. Behavioral testing, immunohistochemistry and electron microscopy were used to explore the effect of these electroacupuncture frequencies used on maintaining the structural integrity of ischemic brain tissue. Compared with the model and 100 Hz electroacupuncture groups the 15 and 30 Hz electroacupuncture groups displayed decreased neurological deficit scores, as evaluated by the "Longa" method, significantly increased glial fibrillary acidic protein expression, and alleviated ultrastructural damage of astrocytes at the edge of the infarct. Our experimental findings indicate that 15 and 30 Hz electroacupuncture intervention can favorably maintain the structural integrity of astrocytes and play a protective role in cerebral ischemic injury. Astrocyte structural integrity may be the mechanism underlying acupuncture production of ischemic tolerance展开更多
Scutellarin, a bioactive flavone isolated from Scutellaria baicalensis, has anti-inflammatory, anti-neurotoxic, anti-apoptotic and anti-oxida- tive effects and has been used to treat cardiovascular and cerebrovascular...Scutellarin, a bioactive flavone isolated from Scutellaria baicalensis, has anti-inflammatory, anti-neurotoxic, anti-apoptotic and anti-oxida- tive effects and has been used to treat cardiovascular and cerebrovascular diseases in China. However, the mechanisms by which scutellarin mediates neuroprotection in cerebral ischemia remain unclear. The interaction between scutellarin and nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) was assessed by molecular docking study, which showed that scutellarin selectively binds to NOX2 with high affinity. Cultures of primary astrocytes isolated from the cerebral cortex of neonatal Sprague-Dawley rats were pretreated with 2, 10 or 50 μM scutellarin for 30 minutes. The astrocytes were then subjected to oxygen/glucose deprivation by incubation for 2 hours in glucose-free Dulbecco's modified Eagle's medium in a 95% N2/5% CO2 incubator, followed by simulated reperfusion for 22 hours. Cell viability was assessed by cell counting kit-8 assay. Expression levels of NOX2, connexin 43 and caspase-3 were assessed by western blot assay. Reactive oxygen species were measured spectrophotometrically. Pretreatment with 10 or 50 μM scutellarin substantially increased viability, reduced the expression of NOX2 and caspase-3, increased the expression of connexin 43, and diminished the levels of reactive oxygen, species in astrocytes subjected to ischemia-'reperfusion. We also assessed the effects of scutellarin in vivo in the rat transient middle cerebral artery occlusion model of cerebral ischemia-reperfusion injury. Rats were given intraperitoneal injection of 100 mg/kg scutellarin 2 hours before surgery. The Bederson scale was used to assess neurological deficit, and 2,3,5-triphenyltetrazolium chloride staining was used to measure infarct size. Western blot assay was used to assess expression of NOX2 and connexin 43 in brain tissue. Enzyme-linked immunosorbent assay was used to detect 8-hydroxydeoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (4-HNE) and 3-nitrotyrosin (3-NT) in brain tissue. Immunofluorescence double staining was used to determine the co-expression of caspase-3 and NeuN. Pretreatment with scutellarin im- proved the neurological function of rats with focal cerebral ischemia, reduced infarct size, diminished the expression of NOX2, reduced levels of 8-OHdG, 4-HNE and 3-NT, and reduced the number of cells co-expressing caspase-3 and NeuN in the injured brain tissue. Furthermore, we examined the effect of the NOX2 inhibitor apocynin. Apocynin substantially increased connexin 43 expression in vivo and in vitro. Collectively, our findings suggest that scutellarin protects against ischemic injury in vitro and in vivo by downregulating NOX2, upregulating connexin 43, decreasing oxidative damage, and reducing apoptotic cell death.展开更多
Cerebral ischemic injury is the main manifestation of stroke,and its incidence in stroke patients is 70–80%.Although ischemic stroke can be treated with tissue-type plasminogen activator,its time window of effectiven...Cerebral ischemic injury is the main manifestation of stroke,and its incidence in stroke patients is 70–80%.Although ischemic stroke can be treated with tissue-type plasminogen activator,its time window of effectiveness is narrow.Therefore,the incidence of paralysis,hypoesthesia,aphasia,dysphagia,and cognitive impairment caused by cerebral ischemia is high.Nerve tissue regeneration can promote the recovery of the aforementioned dysfunction.Neural stem cells can participate in the reconstruction of the damaged nervous system and promote the recovery of nervous function during self-repair of damaged brain tissue.Neural stem cell transplantation for ischemic stroke has been a hot topic for more than 10 years.This review discusses the treatment of ischemic stroke with neural stem cells,as well as the mechanisms of their involvement in stroke treatment.展开更多
BACKGROUND: Due to collateral circulation and cerebrovascular reserve, arterial stenosis and reduced cerebral blood flow may not necessarily indicate impaired cerebral peffusion. Therefore, according to degree of ste...BACKGROUND: Due to collateral circulation and cerebrovascular reserve, arterial stenosis and reduced cerebral blood flow may not necessarily indicate impaired cerebral peffusion. Therefore, according to degree of stenosis and clinical symptoms, interventional surgery to relieve arterial stenosis in transient ischemic attack (TIA) patients with major intracranial stenosis is imprudent. Rather, cerebral perfusion and reserve capacity are direct indicators for the assessment of degree and presence of cerebral ischemia. OBJECTIVE: To evaluate cerebral perfusion and reserve in TIA patients with major intracranial stenosis or occlusion using magnetic resonance-perfusion-weighted imaging (MR-PWl) data prior to and following diamox administration. DESIGN, TIME AND SETTING: A self-comparative, neuroimaging observation was performed at the Neurological Department and Radiological Center of the First Affiliated Hospital of Jinan University between December 2007 and April 2009. PARTICIPANTS: Seven acute TIA patients, who were admitted to the Neurological Department of the First Affiliated Hospital of Jinan University between December 2007 and April 2009, were enrolled in the present study. Magnetic resonance imaging confirmed that no acute cerebral infarction happened, nor did bleeding exist. Magnetic resonance angiography, transcranial Doppler ultrasound, and/or digital subtraction angiography confirmed the presence of major intracranial arterial stenosis. Clinical symptoms corresponded to blood supplying regions of the arterial stenosis. METHODS: Baseline MR-PWI was performed on seven patients with intracranial stenosis or occlusion. Two grams of acetazolamide (diamox) were orally administered after 2 days. A second PWl was performed after 2 hours to compare cerebral perfusion parameters prior to and following diamox administration. MAIN OUTCOME MEASURES: PWI results of cerebral perfusion prior to and following diamox administration. RESULTS: The baseline PWl from five patients indicated decreased cerebral perfusion areas. Following oral administration of diamox, cerebral perfusion significantly decreased in those areas. Moreover, new areas of decreased cerebral perfusion were observed in two out of the five patients. In one patient, no significant decrease in cerebral perfusion was found. In another patient, baseline PWl indicated decreased cerebral perfusion in the left hemisphere. However, normal perfusion was observed in both cerebral lobes following diamox administration. CONCLUSION: TIA patients with intracranial stenosis, who are diagnosed by PWI and exhibited decreased cerebral perfusion and reserve, might require further treatment such as intervention by angioptasty.展开更多
During the previous years, with the emerging of nanotechnology, the enormous capabilities of nanoparticles have drawn great attention from researchers in terms of their potentials in various aspects of pharmacology. C...During the previous years, with the emerging of nanotechnology, the enormous capabilities of nanoparticles have drawn great attention from researchers in terms of their potentials in various aspects of pharmacology. Cerium oxide nanoparticles(nanoceria), considered as one of the most widely used nanomaterials, due to its tempting catalytic antioxidant properties, show a promising potential in diverse disorders, such as cerebral ischemic stroke(CIS), cancer, neurodegenerative and inflammatory diseases. Overwhelming generation of reactive oxygen species(ROS) and reactive nitrogen species(RNS) during cerebral ischemia and reperfusion periods is known to aggravate brain damage via sophisticated cellular and molecular mechanisms, and therefore exploration of the antioxidant capacities of nanoceria becomes a new approach in reducing cerebral ischemic injury. Furthermore, utilizing nanoceria as a drug carrier might display the propensity to overcome limitations or inefficacy of other conceivable neuroprotectants and exhibit synergistic effects. In this review, we emphasize on the principle features of nanoceria and current researches concerning nanoceria as a potential therapeutic agent or carrier in improving the prognosis of CIS.展开更多
BACKGROUND: Adenovirus has been used to develop neuroglobin (Ngb) vectors. Although transfection efficiency is high, induced gene mutation, cytotoxicity, inflammation, and low exogenous gene content have limited it...BACKGROUND: Adenovirus has been used to develop neuroglobin (Ngb) vectors. Although transfection efficiency is high, induced gene mutation, cytotoxicity, inflammation, and low exogenous gene content have limited its application. OBJECTIVE: To observe the effects of recombinant Ngb plasmid in a rat model of focal cerebral ischemia. DESIGN, TIME AND SETTING: Genetically engineered, randomized, controlled, animal experiment was performed at the Laboratory of Chongqing Medical University from May 2006 and January 2007. MATERIALS: 2, 3, 5-triphenyltetrazolium chloride was purchased from Shanghai Sangon Biological Engineering Technology and Services. Rabbit anti-rat Bcl-2 polyclonal antibody, rabbit anti-rat β-actin monoclonal antibody, and FITC-labeled goat anti-rabbit IgG were purchased from Sigma, USA. TUNEL apoptosis kit was purchased from Roche, Germany. METHODS: A total of 54 male, adult, Wistar rats were randomly assigned to 3 groups (n=18): normal saline, plasmid control, and recombinant Ngb (pCDNA3.1 (+)/Ngb). Normal saline, plasmid pCDNA3.1 (+), and recombinant plasmid pCDNA3.1 (+)/Ngb were separately injected into two sites in the rat cerebral cortex, and models of focal ischemia were established by occlusion of the right middle cerebral artery after 24 hours. MAIN OUTCOME MEASURES: Local ischemic damage was detected by 2, 3, 5- triphenyltetrazolium chloride staining, apoptosis in the penumbra was confirmed using the TUNEL method, and Bcl-2 protein expression in the penumbra was determined by indirect immunofluorescent staining and Western blot analysis. RESULTS: Compared with the normal saline and plasmid control groups, cerebral infarction size and the number of apoptotic cells in the pCDNA3.1 (+)/Ngb group were significantly reduced (P 〈 0.01). The percentage of Bcl-2-positive cells in the penumbra of the pCDNA3.1 (+)/Ngb group was significantly increased (P 〈 0.01). The relative expression level of Bcl-2 protein was increased by 40%-50%. CONCLUSION: Recombinant plasmid pCDNA3.1/Ngb provides neuroprotection by upregulating Bcl-2 expression and inhibiting cell apoptosis in the penumbra.展开更多
The present study investigated the effects of the mitochondrial calcium uniporter inhibitor ruthenium red and the agonist spermine on cerebral edema in rats with cerebral ischemia reperfusion injury. Left middle cereb...The present study investigated the effects of the mitochondrial calcium uniporter inhibitor ruthenium red and the agonist spermine on cerebral edema in rats with cerebral ischemia reperfusion injury. Left middle cerebral artery occlusion (MCAO) was induced in rats using the suture method. Following 24 hours of ischemic reperfusion, neurological function scores of rats with MCAO, and rats pretreated with ruthenium red and spermine were significantly lower, however, water content of brain tissue, aquaporin 4 expression and immunoglobulin G (IgG) exudation were significantly higher than those of sham-operated rats. Compared with MCAO rats and spermine-treated rats, neurological function scores were considerably higher, and brain tissue water content, aquaporin 4 expression and IgG exudation decreased in ruthenium red-treated rats. These findings suggest that preventive application of the mitochondrial calcium uniporter inhibitor ruthenium red can significantly decrease aquaporin 4 and IgG expression, influence the permeability of the blood brain barrier, and thereby decrease the extent of cerebral edema.展开更多
In recent years,a large number of differentially expressed genes have been identified in human umbilical cord mesenchymal stem cell(hUMSC)transplants for the treatment of ischemic cerebral infarction.These genes are i...In recent years,a large number of differentially expressed genes have been identified in human umbilical cord mesenchymal stem cell(hUMSC)transplants for the treatment of ischemic cerebral infarction.These genes are involved in various biochemical processes,but the role of microRNAs(miRNAs)in this process is still unclear.From the Gene Expression Omnibus(GEO)database,we downloaded two microarray datasets for GSE78731(messenger RNA(mRNA)profile)and GSE97532(miRNA profile).The differentially expressed genes screened were compared between the hUMSC group and the middle cerebral artery occlusion group.Gene ontology enrichment and pathway enrichment analyses were subsequently conducted using the online Database for Annotation,Visualization,and Integrated Discovery.Identified genes were applied to perform weighted gene co-suppression analyses,to establish a weighted co-expression network model.Furthermore,the protein-protein interaction network for differentially expressed genes from turquoise modules was built using Cytoscape(version 3.40)and the most highly correlated subnetwork was extracted from the protein-protein interaction network using the MCODE plugin.The predicted target genes for differentially expressed miRNAs were also identified using the online database starBase v3.0.A total of 3698 differentially expressed genes were identified.Gene ontology analysis demonstrated that differentially expressed genes that are related to hUMSC treatment of ischemic cerebral infarction are involved in endocytosis and inflammatory responses.We identified 12 differentially expressed miRNAs in middle cerebral artery occlusion rats after hUMSC treatment,and these differentially expressed miRNAs were mainly involved in signaling in inflammatory pathways,such as in the regulation of neutrophil migration.In conclusion,we have identified a number of differentially expressed genes and differentially expressed mRNAs,miRNA-mRNAs,and signaling pathways involved in the hUMSC treatment of ischemic cerebral infarction.Bioinformatics and interaction analyses can provide novel clues for further research into hUMSC treatment of ischemic cerebral infarction.展开更多
Brain-derived neurotrophic factor is associated with the insulin signaling pathway and glucose me- tabolism. We hypothesized that expression of brain-derived neurotrophic factor and its receptor may be involved in glu...Brain-derived neurotrophic factor is associated with the insulin signaling pathway and glucose me- tabolism. We hypothesized that expression of brain-derived neurotrophic factor and its receptor may be involved in glucose intolerance following ischemic stress. To verify this hypothesis, this study aimed to observe the changes in brain-derived neurotrophic factor and tyrosine kinase B receptor expression in glucose metabolism-associated regions following cerebral ischemic stress in mice. At day 1 after middle cerebral artery occlusion, the expression levels of brain-derived neurotrophic factor were significantly decreased in the ischemic cortex, hypothalamus, liver, skeletal muscle, and pancreas. The expression levels of tyrosine kinase B receptor were decreased in the hypothalamus and liver, and increased in the skeletal muscle and pancreas, but remained unchanged in the cortex Intrahypothalamic administration of brain-derived neurotrophic factor (40 ng) suppressed the de- crease in insulin receptor and tyrosine-phosphorylated insulin receptor expression in the liver and skeletal muscle, and inhibited the overexpression of gluconeogenesis-associated phosphoenolpy- ruvate carboxykinase and glucose-6-phosphatase in the liver of cerebral ischemic mice. However, serum insulin levels remained unchanged. Our experimental findings indicate that brain-derived neurotrophic factor can promote glucose metabolism, reduce gluconeogenesis, and decrease blood glucose levels after cerebral ischemic stress. The low expression of brain-derived neurotrophic factor following cerebral ischemia may be involved in the development of glucose intolerance.展开更多
BACKGROUND: Stroke prevention guidelines should be made available application to aid in uniformity, timing, preciseness, and acceptance of disease. OBJECTIVE: To investigate the awareness of neurologists in some Bei...BACKGROUND: Stroke prevention guidelines should be made available application to aid in uniformity, timing, preciseness, and acceptance of disease. OBJECTIVE: To investigate the awareness of neurologists in some Beijing secondary prevention of cerebral infarction/transient ischemia. DESIGN: Cross-sectional study. to neurologists for clinical hospitals of intervention in SETTING: Beijing Tiantan Hospital, Beijing Anzhen Hospital, General Hospital of Beijing Military Area, Command of Chinese PLA, Beijing Chuiyangliu Hospital, Beijing 6^th Hospital, Beijing Hepingli Hospital, and Beijing Daxing District Hospital. PARTICIPANTS: A total of 28 (associate) chief physicians, 58 attending physicians, and 54 resident physicians who engaged in clinical treatment of cerebrovascular diseases were selected from 8 hospitals in Beijing from March to April 2007. All physicians provided informed consent. METHODS: Self-made closed questionnaires were provided for data collection, consisting of 16 questions that were single choice or multiple choice. Specifically, questions 1-7 focused on awareness of blood pressure regulation in different patients and first choice of decompression drug; questions 8-12 focused on awareness of lipid regulation; and questions 13-16 focused on awareness of anti-blood platelet drugs applied in secondary prevention. The scores ranged from 0-100 points, and each question was worth 6.25 points. The scores positively correlated with the awareness rate. To test leveling real-time, the survey lasted for a maximum of 20 minutes. One questionnaire was independently finished by each subject in the survey. MAIN OUTCOME MEASURES: Awareness intervention among neurologists during secondary prevention of cerebral infarction/transient ischemia and questionnaire scores. RESULTS: 140 subjects were included in the final analysis. ① The awareness rate among neurologists for intervention during secondary prevention of cerebral infarction/transient ischemia ranged from 0.7-57.9%, the scores ranged between 0-56 points, and the mean score was 26 points.② Scores of resident physicians were 0-56 points with a mean score of 26 points; attending physicians scored 6-50 points, with a mean score of 26 points; and chief physicians scored 6-50 points, with a mean score of 23 points. There were no significant differences among the various physicians (F = 0.771, t = 0.465, P 〉 0.05). CONCLUSION: Awareness among neurologists of intervention during secondary prevention of cerebral infarction/transient ischemia is not ideal. However, there was no significant difference between professional titles.展开更多
文摘This case report investigates the manifestation of cerebral amyloid angiopathy (CAA) through recurrent Transient Ischemic Attacks (TIAs) in an 82-year-old patient. Despite initial diagnostic complexities, cerebral angiography-MRI revealed features indicative of CAA. Symptomatic treatment resulted in improvement, but the patient later developed a fatal hematoma. The discussion navigates the intricate therapeutic landscape of repetitive TIAs in the elderly with cardiovascular risk factors, emphasizing the pivotal role of cerebral MRI and meticulous bleeding risk management. The conclusion stresses the importance of incorporating SWI sequences, specifically when suspecting a cardioembolic TIA, as a diagnostic measure to explore and exclude CAA in the differential diagnosis. This case report provides valuable insights into these challenges, highlighting the need to consider CAA in relevant cases.
基金supported by the National Natural Science Foundation of China,Nos.82104158(to XT),31800887(to LY),31972902(to LY),82001422(to YL)China Postdoctoral Science Foundation,No.2020M683750(to LY)partially by Young Talent Fund of University Association for Science and Technology in Shaanxi Province of China,No.20200307(to LY).
文摘β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.
基金supported by the National Natural Science Foundation of China,Nos.82171456 (to QY),81971229 (to QY)the Natural Science Foundation of Chongqing,No.cstc2021jcyj-msxmX0263 (to QY)the Postgraduate Research and Innovation Project of Chongqing,Nos.CYB20151 (to QY),CYS19182 (to YC)。
文摘In the central nervous system, the formation of fibrotic scar after injury inhibits axon regeneration and promotes repair. However, the mechanism underlying fibrotic scar formation and regulation remains poorly understood. M2 macrophages regulate fibrotic scar formation after injury to the heart, lung, kidney, and central nervous system. However, it remains to be clarified whether and how M2 macrophages regulate fibrotic scar formation after cerebral ischemia injury. In this study, we found that, in a rat model of cerebral ischemia induced by middle cerebral artery occlusion/reperfusion, fibrosis and macrophage infiltration were apparent in the ischemic core in the early stage of injury(within 14 days of injury). The number of infiltrated macrophages was positively correlated with fibronectin expression. Depletion of circulating monocyte-derived macrophages attenuated fibrotic scar formation. Interleukin 4(IL4) expression was strongly enhanced in the ischemic cerebral tissues, and IL4-induced M2 macrophage polarization promoted fibrotic scar formation in the ischemic core. In addition, macrophage-conditioned medium directly promoted fibroblast proliferation and the production of extracellular matrix proteins in vitro. Further pharmacological and genetic analyses showed that sonic hedgehog secreted by M2 macrophages promoted fibrogenesis in vitro and in vivo, and that this process was mediated by secretion of the key fibrosis-associated regulatory proteins transforming growth factor beta 1 and matrix metalloproteinase 9. Furthermore, IL4-afforded functional restoration on angiogenesis, cell apoptosis, and infarct volume in the ischemic core of cerebral ischemia rats were markedly impaired by treatment with an sonic hedgehog signaling inhibitor, paralleling the extent of fibrosis. Taken together, our findings show that IL4/sonic hedgehog/transforming growth factor beta 1 signaling targeting macrophages regulates the formation of fibrotic scar and is a potential therapeutic target for ischemic stroke.
基金supported by the National Natural Science Foundation of China,No.81730050(to WH).
文摘In vivo imaging of cerebral ischemia/reperfusion injury remains an important challenge.We injected porous Ag/Au@SiO_(2) bimetallic hollow nanoshells carrying anti-tropomyosin 4 as a molecular probe into mice with cerebral ischemia/reperfusion injury and observed microvascular changes in the brain using photoacoustic imaging with ultrasonography.At each measured time point,the total photoacoustic signal was significantly higher on the affected side than on the healthy side.Twelve hours after reperfusion,cerebral perfusion on the affected side increased,cerebrovascular injury worsened,and anti-tropomyosin 4 expression increased.Twenty-four hours after reperfusion and later,perfusion on the affected side declined slowly and stabilized after 1 week;brain injury was also alleviated.Histopathological and immunohistochemical examinations confirmed the brain injury tissue changes.The nanoshell molecular probe carrying anti-tropomyosin 4 has potential for use in early diagnosis of cerebral ischemia/reperfusion injury and evaluating its progression.
文摘Neuroprotection by ischemic preconditioning has been confirmed by many studies, but the precise mechanism remains unclear. In the present study, we performed cerebral ischemic pre- conditioning in rats by simulating a transient ischemic attack twice (each a 20-minute occlusion of the middle cerebral artery) before inducing focal cerebral infarction (2 hour occlusion-reper- fusion in the same artery). We also explored the mechanism underlying the neuroprotective effect of ischemic preconditioning. Seven days after ocdusion-reperfusion, tetrazolium chloride staining and immunohistochemistry revealed that the infarct volume was significantly smaller in the group that underwent preconditioning than in the model group. Furthermore, vascular endothelial growth factor immunoreactivity was considerably greater in the hippocampal CA3 region of preconditioned rats than model rats. Our results suggest that the protective effects of ischemic preconditioning on focal cerebral infarction are associated with upregulation of vascu- lar endothelial growth factor.
基金National Natural Science Foundation of China(U140222181373997+6 种基金81573640815736368160331581603316)Beijing Natural Science Foundation (7161011)CAMS Innovation Fundfor Medical Sciences (CIFMS) ( 2016-I2M-1-004)Key Research and Development Project of Hun
文摘Ischemic stroke(IS) is a disease caused by deficiency of blood and oxygen in focal or complete brain,followed by inflammation cascade and other pathological reactions,which finally lead to irreversible damage to the cerebrum.For the inflammation is a key progress at the initiation of ischemia and poststroke,and chemokines work as vital cytokines in inflammation,we focus the roles of chemokines in IS.Studies have shown cerebral ischemia is associated with marked induction of both CXC and CC chemokines which resulting in extensive leukocyte infiltration in the ischemic brain,and neutrophil infiltration may increase cerebral edema inducing injury in the ischemic area.In addition,chemokines also shows other functions such as promote neuroblast migration,hematogenous cell recruitment and functional brain repair.Thus,a similar chemokine ligand/chemokine receptor pair can mediate both beneficial and detrimental effects depending on the window of observation and pathophysiological conditions.This manuscript reviews the studies about chemokine-mediated effects in cerebral ischemia/reperfusion and discusses the potential significance of these interactions in injury and repair of ischemic tissues.We also refer drug development based on the chemokines and clinical applications using chemokines as diagnostic or prognostic biomarkers in ischemic stroke.
基金supported by the Natural Science Foundation(Joint Fund)of Liaoning Provincial Science and Technology Department,No.2013022021
文摘It is difficult to control the degree of ischemic postconditioning in the brain and other isch- emia-sensitive organs. Remote ischemic postconditioning could protect some ischemia-sensitive organs through measures on terminal organs. In this study, a focal cerebral ischemia-reperftlsion injury model was established using three cycles of remote ischernic postconditioning, each cycle consisted of 10-minute occlusion of the femoral artery and 10-minute opening. The results showed that, remote ischemic postconditioning significantly decreased the percentage of the in- farct area and attenuated brain edema. In addition, inflammatory nuclear factor-KB expression was significantly lower, while anti-apoptotic Bcl-2 expression was significantly elevated in the ce- rebral cortex on the ischemic side. Our findings indicate that remote ischemic postconditioning attenuates focal cerebral ischemia/reperfusion injury, and that the neuroprotective mechanism is mediated by an anti-apoptotic effect and reduction of the inflammatory response.
基金supported by the National Natural Science Foundation of China, No. 30960399, 81160181
文摘To investigate the effects of mRNA interference on aquaporin-4 expression in swollen tissue of rats with ischemic cerebral edema, and diagnose the significance of diffusion-weighted MRI, we injected 5 pL shRNA- aquaporin-4 (control group) or siRNA- aquaporin-4 solution (1:800) (RNA interference group) into the rat right basal ganglia immediately before occlusion of the middle cerebral artery. At 0.25 hours after occlusion of the middle cerebral artery, diffusion-weighted MRI displayed a high signal; within 2 hours, the relative apparent diffusion coefficient decreased markedly, aquaporin-4 expression increased rapidly, and intracellular edema was obviously aggravated; at 4 and 6 hours, the relative apparent diffusion coefficient slowly returned to control levels, aquaporin-4 expression slightly increased, and angioedema was observed. In the RNA interference group, during 0.25- 6 hours after injection of siRNA- aquaporin-4 solution, the relative apparent diffusion coefficient slightly fluctuated and aquaporin-4 expression was upregulated; during 0.5 4 hours, the relative apparent diffusion coefficient was significantly higher, while aquaporin-4 expression was significantly lower when compared with the control group, and intracellular edema was markedly reduced; at 0.25 and 6 hours, the relative apparent diffusion coefficient and aquaporin-4 expression were similar when compared with the control group; obvious angioedema remained at 6 hours. Pearson's correlation test results showed that aquaporin-4 expression was negatively correlated with the apparent diffusion coefficient (r = -0.806, P 〈 0.01). These findings suggest that upregulated aquaporin-4 expression is likely to be the main molecular mechanism of intracellular edema and may be the molecular basis for decreased relative apparent diffusion coefficient. Aquaporin-4 gene interference can effectively inhibit the upregulation of aquaporin-4 expression during the stage of intracelfular edema with time-effectiveness. Moreover, diffusion-weighted MRI can accurately detect intracellular edema.
文摘MicroRNAs are a family of small, genome-encoded endogenous RNAs that are transcribed but are not translated into proteins. They serve essential roles in virtually every aspect of brain function, including neurogenesis, neural development, and cellular responses leading to changes in synaptic plasticity. They are also implicated in neurodegeneration and neurological disorders, in responses to hypoxia and ischemia, and in ischemic tolerance induced by ischemic preconditioning. In recent developments, miRNA expres- sion profiling has been examined in stroke, and these studies indicate that miRNAs have emerged as key mediators in ischemic stroke biology. Both increased and decreased miRNA levels may be needed either as prevention or treatment of stroke. Novel approaches are being developed to get miRNA related therapeu- tics into the brain across an intact blood-brain barrier, including chemical modification, use of targeting molecules and methods to disrupt the blood-brain barrier.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(NRF-2017R1D1A1B03033271,to JDK)the Bio-Synergy Research Project(NRF-2018M3A9C4076478,to IJK)of the Ministry of Science,ICT and Future Planning through the National Research Foundation
文摘Recently,we have reported that Oenanthe javanica extract(OJE)displays strong neuroprotective effect against ischemic damage after transient global cerebral ischemia.However,neuroprotective mechanisms of OJE have not been fully identified.Thus,this study investigated the neuroprotection of OJE in the hippocampal CA1 area and its anti-inflammatory activity in gerbils subjected to 5 minutes of transient global cerebral ischemia.We treated the animals by intragastrical injection of OJE(100 and 200 mg/kg)once daily for 1 week prior to transient global cerebral ischemia.Neuroprotection of OJE was observed by immunohistochemistry for neuronal nuclear antigen and histofluorescence staining for Fluoro-Jade B.Immunohistochemistry of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 was done for astrocytosis and microgliosis,respectively.To investigate the neuroprotective mechanisms of OJE,we performed immunohistochemistry of tumor necrosis factor-alpha and interleukin-2 for pro-inflammatory function and interleukin-4 and interleukin-13 for anti-inflammatory function.When we treated the animals by intragastrical administration of 200 mg/kg of OJE,hippocampal CA1 pyramidal neurons were protected from transient global cerebral ischemia and cerebral ischemia-induced gliosis was inhibited in the ischemic hippocampal CA1 area.We also found that interleukin-4 and-13 immunoreactivities were significantly increased in pyramidal neurons of the ischemic CA1 area after OJE pretreatment,and the increased immunoreactivities were sustained in the CA1 pyramidal neurons after transient global cerebral ischemia.However,OJE pretreatment did not increase interleukin-2 and tumor necrosis factor-alpha immunoreactivities in the CA1 pyramidal neurons.Our findings suggest that pretreatment with OJE can protect neurons and attenuate gliosis from transient global cerebral ischemia via increasing expressions of interleukin-4 and-13.The experimental plan of this study was reviewed and approved by the Institutional Animal Care and Use Committee(IACUC)in Kangwon National University(approval No.KW-160802-1)on August 10,2016.
基金supported by a grant from the Guangxi Administration of Traditional Chinese Medicine,No.GZZC0962
文摘The astrocyte is a critical regulator of neuronal survival after ischemic brain injury. Electroacupuncture may be an effective therapy for cerebral ischemia, as electroacupuncture frequency can affect the structural integdty of astrocytes. In this study, a rat model of middle cerebral artery occlusion established using the modified thread embolism method was treated with electroacupuncture of the bilateral Quchi (Llll) and Zusanfi (ST36) at 15, 30, and 100 Hz frequencies. Behavioral testing, immunohistochemistry and electron microscopy were used to explore the effect of these electroacupuncture frequencies used on maintaining the structural integrity of ischemic brain tissue. Compared with the model and 100 Hz electroacupuncture groups the 15 and 30 Hz electroacupuncture groups displayed decreased neurological deficit scores, as evaluated by the "Longa" method, significantly increased glial fibrillary acidic protein expression, and alleviated ultrastructural damage of astrocytes at the edge of the infarct. Our experimental findings indicate that 15 and 30 Hz electroacupuncture intervention can favorably maintain the structural integrity of astrocytes and play a protective role in cerebral ischemic injury. Astrocyte structural integrity may be the mechanism underlying acupuncture production of ischemic tolerance
基金financially supported by the National Natural Science Foundation of China,No.81303115,81774042,81771353the Natural Science Foundation of Guangdong Province of China,No.S2013040016915+3 种基金the Science and Technology Program of Guangzhou City of China,No.201508020050,201604020003the Pearl River S&T Nova Program of Guangzhou,the Postdoctoral Foundation of China,No.BBK42913K09,201003345,BBH429151701a grant from the Hong Kong Scholar Program,Guangzhou University of TCM 2017 High Level University Construction Program,No.A1-AFD018171Z11096a grant from the Specialty Program of Guangdong Province Hospital of Traditional Chinese Medicine of China,No.YN2016MJ07,YN2015QN16,YN2015B2025
文摘Scutellarin, a bioactive flavone isolated from Scutellaria baicalensis, has anti-inflammatory, anti-neurotoxic, anti-apoptotic and anti-oxida- tive effects and has been used to treat cardiovascular and cerebrovascular diseases in China. However, the mechanisms by which scutellarin mediates neuroprotection in cerebral ischemia remain unclear. The interaction between scutellarin and nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) was assessed by molecular docking study, which showed that scutellarin selectively binds to NOX2 with high affinity. Cultures of primary astrocytes isolated from the cerebral cortex of neonatal Sprague-Dawley rats were pretreated with 2, 10 or 50 μM scutellarin for 30 minutes. The astrocytes were then subjected to oxygen/glucose deprivation by incubation for 2 hours in glucose-free Dulbecco's modified Eagle's medium in a 95% N2/5% CO2 incubator, followed by simulated reperfusion for 22 hours. Cell viability was assessed by cell counting kit-8 assay. Expression levels of NOX2, connexin 43 and caspase-3 were assessed by western blot assay. Reactive oxygen species were measured spectrophotometrically. Pretreatment with 10 or 50 μM scutellarin substantially increased viability, reduced the expression of NOX2 and caspase-3, increased the expression of connexin 43, and diminished the levels of reactive oxygen, species in astrocytes subjected to ischemia-'reperfusion. We also assessed the effects of scutellarin in vivo in the rat transient middle cerebral artery occlusion model of cerebral ischemia-reperfusion injury. Rats were given intraperitoneal injection of 100 mg/kg scutellarin 2 hours before surgery. The Bederson scale was used to assess neurological deficit, and 2,3,5-triphenyltetrazolium chloride staining was used to measure infarct size. Western blot assay was used to assess expression of NOX2 and connexin 43 in brain tissue. Enzyme-linked immunosorbent assay was used to detect 8-hydroxydeoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (4-HNE) and 3-nitrotyrosin (3-NT) in brain tissue. Immunofluorescence double staining was used to determine the co-expression of caspase-3 and NeuN. Pretreatment with scutellarin im- proved the neurological function of rats with focal cerebral ischemia, reduced infarct size, diminished the expression of NOX2, reduced levels of 8-OHdG, 4-HNE and 3-NT, and reduced the number of cells co-expressing caspase-3 and NeuN in the injured brain tissue. Furthermore, we examined the effect of the NOX2 inhibitor apocynin. Apocynin substantially increased connexin 43 expression in vivo and in vitro. Collectively, our findings suggest that scutellarin protects against ischemic injury in vitro and in vivo by downregulating NOX2, upregulating connexin 43, decreasing oxidative damage, and reducing apoptotic cell death.
基金supported by the National Natural Science Foundation of China,No.0040205401797(to QG)the General Research Fund of China,No.15164216(to BWML)
文摘Cerebral ischemic injury is the main manifestation of stroke,and its incidence in stroke patients is 70–80%.Although ischemic stroke can be treated with tissue-type plasminogen activator,its time window of effectiveness is narrow.Therefore,the incidence of paralysis,hypoesthesia,aphasia,dysphagia,and cognitive impairment caused by cerebral ischemia is high.Nerve tissue regeneration can promote the recovery of the aforementioned dysfunction.Neural stem cells can participate in the reconstruction of the damaged nervous system and promote the recovery of nervous function during self-repair of damaged brain tissue.Neural stem cell transplantation for ischemic stroke has been a hot topic for more than 10 years.This review discusses the treatment of ischemic stroke with neural stem cells,as well as the mechanisms of their involvement in stroke treatment.
基金Medical Scientific and Technological Research Foundation of Guangdong Province, No. 2007332 2009360the Natural Science Foundation of Guangdong Province, No. 9451063201002951
文摘BACKGROUND: Due to collateral circulation and cerebrovascular reserve, arterial stenosis and reduced cerebral blood flow may not necessarily indicate impaired cerebral peffusion. Therefore, according to degree of stenosis and clinical symptoms, interventional surgery to relieve arterial stenosis in transient ischemic attack (TIA) patients with major intracranial stenosis is imprudent. Rather, cerebral perfusion and reserve capacity are direct indicators for the assessment of degree and presence of cerebral ischemia. OBJECTIVE: To evaluate cerebral perfusion and reserve in TIA patients with major intracranial stenosis or occlusion using magnetic resonance-perfusion-weighted imaging (MR-PWl) data prior to and following diamox administration. DESIGN, TIME AND SETTING: A self-comparative, neuroimaging observation was performed at the Neurological Department and Radiological Center of the First Affiliated Hospital of Jinan University between December 2007 and April 2009. PARTICIPANTS: Seven acute TIA patients, who were admitted to the Neurological Department of the First Affiliated Hospital of Jinan University between December 2007 and April 2009, were enrolled in the present study. Magnetic resonance imaging confirmed that no acute cerebral infarction happened, nor did bleeding exist. Magnetic resonance angiography, transcranial Doppler ultrasound, and/or digital subtraction angiography confirmed the presence of major intracranial arterial stenosis. Clinical symptoms corresponded to blood supplying regions of the arterial stenosis. METHODS: Baseline MR-PWI was performed on seven patients with intracranial stenosis or occlusion. Two grams of acetazolamide (diamox) were orally administered after 2 days. A second PWl was performed after 2 hours to compare cerebral perfusion parameters prior to and following diamox administration. MAIN OUTCOME MEASURES: PWI results of cerebral perfusion prior to and following diamox administration. RESULTS: The baseline PWl from five patients indicated decreased cerebral perfusion areas. Following oral administration of diamox, cerebral perfusion significantly decreased in those areas. Moreover, new areas of decreased cerebral perfusion were observed in two out of the five patients. In one patient, no significant decrease in cerebral perfusion was found. In another patient, baseline PWl indicated decreased cerebral perfusion in the left hemisphere. However, normal perfusion was observed in both cerebral lobes following diamox administration. CONCLUSION: TIA patients with intracranial stenosis, who are diagnosed by PWI and exhibited decreased cerebral perfusion and reserve, might require further treatment such as intervention by angioptasty.
文摘During the previous years, with the emerging of nanotechnology, the enormous capabilities of nanoparticles have drawn great attention from researchers in terms of their potentials in various aspects of pharmacology. Cerium oxide nanoparticles(nanoceria), considered as one of the most widely used nanomaterials, due to its tempting catalytic antioxidant properties, show a promising potential in diverse disorders, such as cerebral ischemic stroke(CIS), cancer, neurodegenerative and inflammatory diseases. Overwhelming generation of reactive oxygen species(ROS) and reactive nitrogen species(RNS) during cerebral ischemia and reperfusion periods is known to aggravate brain damage via sophisticated cellular and molecular mechanisms, and therefore exploration of the antioxidant capacities of nanoceria becomes a new approach in reducing cerebral ischemic injury. Furthermore, utilizing nanoceria as a drug carrier might display the propensity to overcome limitations or inefficacy of other conceivable neuroprotectants and exhibit synergistic effects. In this review, we emphasize on the principle features of nanoceria and current researches concerning nanoceria as a potential therapeutic agent or carrier in improving the prognosis of CIS.
基金a Grant from Chongqing Health Bureau, No. 06-2-177
文摘BACKGROUND: Adenovirus has been used to develop neuroglobin (Ngb) vectors. Although transfection efficiency is high, induced gene mutation, cytotoxicity, inflammation, and low exogenous gene content have limited its application. OBJECTIVE: To observe the effects of recombinant Ngb plasmid in a rat model of focal cerebral ischemia. DESIGN, TIME AND SETTING: Genetically engineered, randomized, controlled, animal experiment was performed at the Laboratory of Chongqing Medical University from May 2006 and January 2007. MATERIALS: 2, 3, 5-triphenyltetrazolium chloride was purchased from Shanghai Sangon Biological Engineering Technology and Services. Rabbit anti-rat Bcl-2 polyclonal antibody, rabbit anti-rat β-actin monoclonal antibody, and FITC-labeled goat anti-rabbit IgG were purchased from Sigma, USA. TUNEL apoptosis kit was purchased from Roche, Germany. METHODS: A total of 54 male, adult, Wistar rats were randomly assigned to 3 groups (n=18): normal saline, plasmid control, and recombinant Ngb (pCDNA3.1 (+)/Ngb). Normal saline, plasmid pCDNA3.1 (+), and recombinant plasmid pCDNA3.1 (+)/Ngb were separately injected into two sites in the rat cerebral cortex, and models of focal ischemia were established by occlusion of the right middle cerebral artery after 24 hours. MAIN OUTCOME MEASURES: Local ischemic damage was detected by 2, 3, 5- triphenyltetrazolium chloride staining, apoptosis in the penumbra was confirmed using the TUNEL method, and Bcl-2 protein expression in the penumbra was determined by indirect immunofluorescent staining and Western blot analysis. RESULTS: Compared with the normal saline and plasmid control groups, cerebral infarction size and the number of apoptotic cells in the pCDNA3.1 (+)/Ngb group were significantly reduced (P 〈 0.01). The percentage of Bcl-2-positive cells in the penumbra of the pCDNA3.1 (+)/Ngb group was significantly increased (P 〈 0.01). The relative expression level of Bcl-2 protein was increased by 40%-50%. CONCLUSION: Recombinant plasmid pCDNA3.1/Ngb provides neuroprotection by upregulating Bcl-2 expression and inhibiting cell apoptosis in the penumbra.
基金the National Natural Science Foundation of China, No. 30972855/C160203
文摘The present study investigated the effects of the mitochondrial calcium uniporter inhibitor ruthenium red and the agonist spermine on cerebral edema in rats with cerebral ischemia reperfusion injury. Left middle cerebral artery occlusion (MCAO) was induced in rats using the suture method. Following 24 hours of ischemic reperfusion, neurological function scores of rats with MCAO, and rats pretreated with ruthenium red and spermine were significantly lower, however, water content of brain tissue, aquaporin 4 expression and immunoglobulin G (IgG) exudation were significantly higher than those of sham-operated rats. Compared with MCAO rats and spermine-treated rats, neurological function scores were considerably higher, and brain tissue water content, aquaporin 4 expression and IgG exudation decreased in ruthenium red-treated rats. These findings suggest that preventive application of the mitochondrial calcium uniporter inhibitor ruthenium red can significantly decrease aquaporin 4 and IgG expression, influence the permeability of the blood brain barrier, and thereby decrease the extent of cerebral edema.
基金supported by the National Key Research&Development Program of China,No.2016YFC1301600Program for Jilin University Science and Technology Innovation Team,No.2017TD-12(both to YY)
文摘In recent years,a large number of differentially expressed genes have been identified in human umbilical cord mesenchymal stem cell(hUMSC)transplants for the treatment of ischemic cerebral infarction.These genes are involved in various biochemical processes,but the role of microRNAs(miRNAs)in this process is still unclear.From the Gene Expression Omnibus(GEO)database,we downloaded two microarray datasets for GSE78731(messenger RNA(mRNA)profile)and GSE97532(miRNA profile).The differentially expressed genes screened were compared between the hUMSC group and the middle cerebral artery occlusion group.Gene ontology enrichment and pathway enrichment analyses were subsequently conducted using the online Database for Annotation,Visualization,and Integrated Discovery.Identified genes were applied to perform weighted gene co-suppression analyses,to establish a weighted co-expression network model.Furthermore,the protein-protein interaction network for differentially expressed genes from turquoise modules was built using Cytoscape(version 3.40)and the most highly correlated subnetwork was extracted from the protein-protein interaction network using the MCODE plugin.The predicted target genes for differentially expressed miRNAs were also identified using the online database starBase v3.0.A total of 3698 differentially expressed genes were identified.Gene ontology analysis demonstrated that differentially expressed genes that are related to hUMSC treatment of ischemic cerebral infarction are involved in endocytosis and inflammatory responses.We identified 12 differentially expressed miRNAs in middle cerebral artery occlusion rats after hUMSC treatment,and these differentially expressed miRNAs were mainly involved in signaling in inflammatory pathways,such as in the regulation of neutrophil migration.In conclusion,we have identified a number of differentially expressed genes and differentially expressed mRNAs,miRNA-mRNAs,and signaling pathways involved in the hUMSC treatment of ischemic cerebral infarction.Bioinformatics and interaction analyses can provide novel clues for further research into hUMSC treatment of ischemic cerebral infarction.
基金supported by the Talent Foundation of the Affiliated Hospital of Guangxi Medical College in China,No.08026Youth Researcher Foundation of Guangxi Medical College in China,No.08012Scientific Research Foundation from Science and Technology Bureau of Shanghai City,No.074119048
文摘Brain-derived neurotrophic factor is associated with the insulin signaling pathway and glucose me- tabolism. We hypothesized that expression of brain-derived neurotrophic factor and its receptor may be involved in glucose intolerance following ischemic stress. To verify this hypothesis, this study aimed to observe the changes in brain-derived neurotrophic factor and tyrosine kinase B receptor expression in glucose metabolism-associated regions following cerebral ischemic stress in mice. At day 1 after middle cerebral artery occlusion, the expression levels of brain-derived neurotrophic factor were significantly decreased in the ischemic cortex, hypothalamus, liver, skeletal muscle, and pancreas. The expression levels of tyrosine kinase B receptor were decreased in the hypothalamus and liver, and increased in the skeletal muscle and pancreas, but remained unchanged in the cortex Intrahypothalamic administration of brain-derived neurotrophic factor (40 ng) suppressed the de- crease in insulin receptor and tyrosine-phosphorylated insulin receptor expression in the liver and skeletal muscle, and inhibited the overexpression of gluconeogenesis-associated phosphoenolpy- ruvate carboxykinase and glucose-6-phosphatase in the liver of cerebral ischemic mice. However, serum insulin levels remained unchanged. Our experimental findings indicate that brain-derived neurotrophic factor can promote glucose metabolism, reduce gluconeogenesis, and decrease blood glucose levels after cerebral ischemic stress. The low expression of brain-derived neurotrophic factor following cerebral ischemia may be involved in the development of glucose intolerance.
基金Key Research Task of Science and Technology Department of Beijing, No.D0905004000011
文摘BACKGROUND: Stroke prevention guidelines should be made available application to aid in uniformity, timing, preciseness, and acceptance of disease. OBJECTIVE: To investigate the awareness of neurologists in some Beijing secondary prevention of cerebral infarction/transient ischemia. DESIGN: Cross-sectional study. to neurologists for clinical hospitals of intervention in SETTING: Beijing Tiantan Hospital, Beijing Anzhen Hospital, General Hospital of Beijing Military Area, Command of Chinese PLA, Beijing Chuiyangliu Hospital, Beijing 6^th Hospital, Beijing Hepingli Hospital, and Beijing Daxing District Hospital. PARTICIPANTS: A total of 28 (associate) chief physicians, 58 attending physicians, and 54 resident physicians who engaged in clinical treatment of cerebrovascular diseases were selected from 8 hospitals in Beijing from March to April 2007. All physicians provided informed consent. METHODS: Self-made closed questionnaires were provided for data collection, consisting of 16 questions that were single choice or multiple choice. Specifically, questions 1-7 focused on awareness of blood pressure regulation in different patients and first choice of decompression drug; questions 8-12 focused on awareness of lipid regulation; and questions 13-16 focused on awareness of anti-blood platelet drugs applied in secondary prevention. The scores ranged from 0-100 points, and each question was worth 6.25 points. The scores positively correlated with the awareness rate. To test leveling real-time, the survey lasted for a maximum of 20 minutes. One questionnaire was independently finished by each subject in the survey. MAIN OUTCOME MEASURES: Awareness intervention among neurologists during secondary prevention of cerebral infarction/transient ischemia and questionnaire scores. RESULTS: 140 subjects were included in the final analysis. ① The awareness rate among neurologists for intervention during secondary prevention of cerebral infarction/transient ischemia ranged from 0.7-57.9%, the scores ranged between 0-56 points, and the mean score was 26 points.② Scores of resident physicians were 0-56 points with a mean score of 26 points; attending physicians scored 6-50 points, with a mean score of 26 points; and chief physicians scored 6-50 points, with a mean score of 23 points. There were no significant differences among the various physicians (F = 0.771, t = 0.465, P 〉 0.05). CONCLUSION: Awareness among neurologists of intervention during secondary prevention of cerebral infarction/transient ischemia is not ideal. However, there was no significant difference between professional titles.