Beyond wrecking a wall:revisiting the concept of blood–brain barrier breakdown in ischemic stroke

The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain homeostasis.Despite the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its breakdown.Moreover,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be understood.This review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier integrity.By moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier dysfunction.Furthermore,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case study.Through this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.

Non-coding RNAs in acute ischemic stroke:from brain to periphery

Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined.With innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models.Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic stroke.Moreover,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.In particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke.In this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.

Post-acute ischemic stroke hyperglycemia aggravates destruction of the blood-brain barrier

Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation,which is associated with blood-brain barrier disruption.Brain microvascular endothelial cells are a major component of the blood-brain barrier.Intercellular mitochondrial transfer has emerged as a novel paradigm for repairing cells with mitochondrial dysfunction.In this study,we first investigated whether mitochondrial transfer exists between brain microvascular endothelial cells,and then investigated the effects of post-acute ischemic stroke hyperglycemia on mitochondrial transfer between brain microvascular endothelial cells.We found that healthy brain microvascular endothelial cells can transfer intact mitochondria to oxygen glucose deprivation-injured brain microvascular endothelial cells.However,post-oxygen glucose deprivation hyperglycemia hindered mitochondrial transfer and exacerbated mitochondrial dysfunction.We established an in vitro brain microvascular endothelial cell model of the blood-brain barrier.We found that post-acute ischemic stroke hyperglycemia reduced the overall energy metabolism levels of brain microvascular endothelial cells and increased permeability of the blood-brain barrier.In a clinical study,we retrospectively analyzed the relationship between post-acute ischemic stroke hyperglycemia and the severity of hemorrhagic transformation.We found that post-acute ischemic stroke hyperglycemia serves as an independent predictor of severe hemorrhagic transformation.These findings suggest that post-acute ischemic stroke hyperglycemia can aggravate disruption of the blood-brain barrier by inhibiting mitochondrial transfer.

Immune regulation of the gut-brain axis and lung-brain axis involved in ischemic stroke

Local ischemia often causes a series of inflammatory reactions when both brain immune cells and the peripheral immune response are activated.In the human body,the gut and lung are regarded as the key reactional targets that are initiated by brain ischemic attacks.Mucosal microorganisms play an important role in immune regulation and metabolism and affect blood-brain barrier permeability.In addition to the relationship between peripheral organs and central areas and the intestine and lung also interact among each other.Here,we review the molecular and cellular immune mechanisms involved in the pathways of inflammation across the gut-brain axis and lung-brain axis.We found that abnormal intestinal flora,the intestinal microenvironment,lung infection,chronic diseases,and mechanical ventilation can worsen the outcome of ischemic stroke.This review also introduces the influence of the brain on the gut and lungs after stroke,highlighting the bidirectional feedback effect among the gut,lungs,and brain.

Research Progress on Brain-Derived Neurotrophic Factor (BDNF) in the Sequelae of Stroke

The research progress of brain-derived neurotrophic factor (BDNF) in the treatment of sequelae of stroke is an important topic. Stroke is among the diseases with the highest mortality and disability rates among the elderly in China. BDNF plays an important role in the development and functional maintenance of the nervous system. In recent years, the application value of BDNF in rehabilitation therapy has gradually received attention. This study has adopted a systematic literature review method, searched Chinese and English databases, screened relevant studies, and conducted data extraction and quality evaluation. This review systematically introduced the research progress of BDNF in the correlation with post-stroke sequelae, with special attention to its application in post-stroke depression, motor dysfunction, and cognitive dysfunction. The results showed that a decrease in BDNF levels is closely related to the exacerbation of depressive symptoms, limited recovery of motor dysfunction, and the occurrence of cognitive dysfunction. BDNF, as a key neurobiological factor, has shown significant potential in the rehabilitation treatment of stroke. By exploring the potential of BDNF as a therapeutic target to prevent and treat sequelae of ischemic stroke, the current research bottlenecks, and the development trends of future treatment strategies.

Brain Functional Network Changes in Patients with Poststroke Cognitive Impairment Following Acupuncture Therapy

Background: The mechanisms by which acupuncture affects poststroke cognitive impairment (PSCI) remain unclear. Objective: To investigate brain functional network (BFN) changes in patients with PSCI after acupuncture therapy. Methods: Twenty-two PSCI patients who underwent acupuncture therapy in our hospital were enrolled as research subjects. Another 14 people matched for age, sex, and education level were included in the normal control (HC) group. All the subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans;the PSCI patients underwent one scan before acupuncture therapy and another after. The network metric difference between PSCI patients and HCs was analyzed via the independent-sample t test, whereas the paired-sample t test was employed to analyze the network metric changes in PSCI patients before vs. after treatment. Results: Small-world network attributes were observed in both groups for sparsities between 0.1 and 0.28. Compared with the HC group, the PSCI group presented significantly lower values for the global topological properties (γ, Cp, and Eloc) of the brain;significantly greater values for the nodal attributes of betweenness centrality in the CUN. L and the HES. R, degree centrality in the SFGdor. L, PCG. L, IPL. L, and HES. R, and nodal local efficiency in the ORBsup. R, ORBsupmed. R, DCG. L, SMG. R, and TPOsup. L;and decreased degree centrality in the MFG. R, IFGoperc. R, and SOG. R. After treatment, PSCI patients presented increased degree centrality in the LING.L, LING.R, and IOG. L and nodal local efficiency in PHG. L, IOG. R, FFG. L, and the HES. L, and decreased betweenness centrality in the PCG. L and CUN. L, degree centrality in the ORBsupmed. R, and nodal local efficiency in ANG. R. Conclusion: Cognitive decline in PSCI patients may be related to BFN disorders;acupuncture therapy may modulate the topological properties of the BFNs of PSCI patients.

Effects of BYHW Decoction and Its Effective Constituents on the Fluidity of the Cell Membrane in a Stroke-Modeled Rat Brain

With in vitro spin labeling electron spin resonance (ESR) spectroscopy, we have studied the effects of Bu Yang Huan Wu (BYHW) decoction and its effective constituents such as astragaloside IV ferulic acid, chuanxiongzine, rutin, chlorogenic acid, 9,10 dimethoxy pterocarpane 7 O β D glucoside, calycosin, formononetin, calycosin 7 O glucoside, paeoniflorin, paeonal and quercein on the cell membrane fluidity of a rat brain which was modeled after the dual cervical arteries were intercepted and released for realizing an ischemia reperfusion injury which was selected as a brain stroke model. Our results indicated that the cell membrane fluidity in the model group decreased approximately 8% compared with the control group, and after brain cells were incubatied with species, the membrane fluidity could be recovered closely to the control level depending on the BYHW decoction and its different constituents. As the membrane fluidity is a very sensitive biological index which reflectsd the cell status, our method will be useful to study the molecular mechanism of tradition Chinese medicine (TCM) and its combination recipe.

Changes in brain functional network connectivity after stroke

Studies have shown that functional network connection models can be used to study brain net- work changes in patients with schizophrenia. In this study, we inferred that these models could also be used to explore functional network connectivity changes in stroke patients. We used independent component analysis to find the motor areas of stroke patients, which is a novel way to determine these areas. In this study, we collected functional magnetic resonance imaging datasets from healthy controls and right-handed stroke patients following their first ever stroke. Using independent component analysis, six spatially independent components highly correlat- ed to the experimental paradigm were extracted. Then, the functional network connectivity of both patients and controls was established to observe the differences between them. The results showed that there were 11 connections in the model in the stroke patients, while there were only four connections in the healthy controls. Further analysis found that some damaged connections may be compensated for by new indirect connections or circuits produced after stroke. These connections may have a direct correlation with the degree of stroke rehabilitation. Our findings suggest that functional network connectivity in stroke patients is more complex than that in hea- lthy controls, and that there is a compensation loop in the functional network following stroke. This implies that functional network reorganization plays a very important role in the process of rehabilitation after stroke.

Overexpression of brain-derived neurotrophic factor in the hippocampus protects against post-stroke depression

Post-stroke depression is associated with reduced expression of brain-derived neurotrophic factor （BDNF）. In this study, we evaluated whether BDNF overexpression affects depression-like behavior in a rat model of post-stroke depression. The middle cerebral artery was occluded to produce a model of focal cerebral ischemia. These rats were then subjected to isolation-housing combined with chronic unpredictable mild stress to generate a model of post-stroke depression. A BDNF gene lentiviral vector was injected into the hippocampus. At 7 days after injection, western blot assay and real-time quantitative PCR revealed that BDNF expression in the hippo- campus was increased in depressive rats injected with BDNF lentivirus compared with depressive rats injected with control vector. Furthermore, sucrose solution consumption was higher, and horizontal and vertical movement scores were increased in the open field test in these rats as well. These findings suggest that BDNF overexpression in the hippocampus of post-stroke depressive rats alleviates depression-like behaviors.

Attenuated blood-brain barrier dysfunction by XQ-1H following ischemic stroke in hyperlipidemic rats

Following ischemic stroke, blood-brain barrier （BBB） is disrupted and is further aggravated with the corresponding incidence of hyperlipidemia. BBB breakdown promotes inflammation infiltration into the brain, which exacerbates cerebral ischemic injury as a result. Here, we report that 10-O-（N,N-dimethylaminoethyl）-ginkgolide B methanesulfonate （XQ-1H） , a novel analog of ginkgolide B, alleviates BBB breakdown in hyperlipidemic rats and protects endothelial cells against inflammatory response. Middle cerebral artery occlusion （MCAO） modeled is- chemic stroke in rats. Before surgery, these rats were fed a cholesterol-rich diet to induce an experimental hyperlip- idemic condition. Additionally, lipopolysaccharide （LPS） incubation with rat brain microvessel endothelial cells （rBMECs） was applied to mimic hyperlipidemia-induced inflammatory injury of BBB. The results indicated more severe infarct size, increased BBB permeability, excessive secretion of pro-inflammatory cytokines, and exaggerated inflammation infiltration of the brain in hyperlipidemic rats following MCAO when compared to rats fed with normal diet. XQ-1H protected BBB integrity, lessoned brain edema and inflammation penetration, down- regulated MMP- 9 and VCMA-1 expressions, and extenuated ischemic infarction. XQ-1H alleviated LPS-induced inflammatory re- sponse in rBMECs, characterized by promoting cell viability, inhibiting TNF-α, IL-1β, and IL-6 releasing, and downregulating NF-KB inflammatory signal and down- stream proteins, such as VCAM-1 and iNOS. In conclusion, the present study shows that XQ-1H stabilizes BBB function following ischemic stroke in hyperlipidemic rats, and the possible mechanisms may be related to inflammation inhibition.

Tongguan Liqiao acupuncture therapy improves dysphagia after brainstem stroke

Tongguan Liqiao acupuncture therapy has been shown to effectively treat dysphagia after stroke-based pseudobulbar paralysis. We presumed that this therapy would be effective for dysphagia after bulbar paralysis in patients with brainstem infarction. Sixty-four patients with dysphagia following brainstem infarction were recruited and divided into a medulla oblongata infarction group（n = 22）, a midbrain and pons infarction group（n = 16）, and a multiple cerebral infarction group（n = 26） according to their magnetic resonance imaging results. All patients received Tongguan Liqiao acupuncture for 28 days. The main acupoints were Neiguan（PC6）, Renzhong（DU26）, Sanyinjiao（SP6）, Fengchi（GB20）, Wangu（GB12）, and Yifeng（SJ17）. Furthermore, the posterior pharyngeal wall was pricked. Before and after treatment, patient swallowing functions were evaluated with the Kubota Water Test, Fujishima Ichiro Rating Scale, and the Standard Swallowing Assessment. The Barthel Index was also used to evaluate their quality of life. Results showed that after 28 days of treatment, scores on the Kubota Water Test and Standard Swallowing Assessment had decreased, but scores on the Fujishima Ichiro Rating Scale and Barthel Index had increased in each group. The total efficacy rate was 92.2% after treatment, and was most obvious in patients with medulla oblongata infarction（95.9%）. These findings suggest that Tongguan Liqiao acupuncture therapy can repair the connection of upper motor neurons to the medulla oblongata motor nucleus, promote the recovery of brainstem infarction, and improve patient＇s swallowing ability and quality of life.

Differences in brain-derived neurotrophic factor gene polymorphisms between acute ischemic stroke patients and healthy controls in the Han population of southwest China

Single-nucleotide polymorphisms in the brain-derived neurotrophic factor gene may affect the secretion and function of brain-derived neurotrophic factor, thereby affecting the occurrence, severity and prognosis of ischemic stroke. This case-control study included 778 patients (475 males and 303 females, mean age of 64.0 ± 12.6 years) in the acute phase of ischemic stroke and 865 control subjects (438 males and 427 females, mean age of 51.7 ± 14.7 years) from the Department of Neurology, Wes: China Hospital, Sichuan University, China between September 2011 and December 2014. The patients' severities of neurological defici:s in the acute phase were assessed using the National Institutes of Health Stroke Scale immediately after admission to hospital. The ischemic stroke patients were divided into different subtypes according to the Trial of Org 10172 in Acute Stroke Treatment classification. Early prognosis was evaluated using the Modified Rankin Scale when the patients were discharged. Genomic DNA was extracted from peripheral blood of participants. Genotyping of rs7124442 and rs6265 was performed using Kompetitive Allele Specific polymerase chain reaction genotyping technology. Our results demonstrated that patients who carried the C allele of the rs7124442 locus had a lower risk of poor prognosis than the T allele carriers (odds ratio [OR]= 0.67;95% confidence interval [CI]: 0.45-1.00;P = 0.048). The patients with the CC or TC genotype also exhibited lower risk than TT carriers (OR = 0.65;95% CI: 0.42-1.00;P = 0.049). The AA genotype at the rs6265 locus was associated with the occurrence of ischemic stroke in patients with large-artery atherosclerosis (OR = 0.5& 95% CI: 0.37-0.90;P = 0.015). We found that the C allele (CC and TC genotypes) at the rs7124442 locus may be protective for the prognosis of ischemic stroke. The AA genotype at the rs6265 locus is likely a protective factor against the occurrence of ischemic stroke in patients with large-artery atherosclerosis. The study protocol was approved by the Ethics Committee of West China Hospital of Sichuan University, China (approval ID number 2008,4]) on July 25, 2008.

Acupuncture at Waiguan(SJ5) and sham points influences activation of functional brain areas of ischemic stroke patients: a functional magnetic resonance imaging study

Most studies addressing the specificity of meridians and acupuncture points have focused mainly on the different neural effects of acupuncture at different points in healthy individuals. This study examined the effects of acupuncture on brain function in a pathological context. Sixteen patients with ischemic stroke were randomly assigned to true point group （true acupuncture at right Waiguan （SJ5）） and sham point group （sham acupuncture）. Results of functional magnetic resonance imaging revealed activation in right parietal lobe （Brodmann areas 7 and 19）, the right temporal lobe （Brodmann area 39）, the right limbic lobe （Brodmann area 23） and bilateral oc-cipital lobes （Brodmann area 18）. Furthermore, inhibition of bilateral frontal lobes （Brodmann area 4, 6, and 45）, right parietal lobe （Brodmann areas 1 and 5） and left temporal lobe （Brodmann area 21 ） were observed in the true point group. Activation in the precuneus of right parietal lobe （Brodmann area 7） and inhibition of the left superior frontal gyrus （Brodmann area 10） was observed in the sham group. Compared with sham acupuncture, acupuncture at Waiguan in stroke patients inhibited Brodmann area 5 on the healthy side. Results indicated that the altered specificity of sensation-associated cortex （Brodmann area 5） is possibly associated with a central mechanism of acupuncture at Waiguan for stroke patients.

Motor imagery training induces changes in brain neural networks in stroke patients

Motor imagery is the mental representation of an action without overt movement or muscle activation. However, the effects of motor imagery on stroke-induced hand dysfunction and brain neural networks are still unknown. We conducted a randomized controlled trial in the China Rehabilitation Research Center. Twenty stroke patients, including 13 males and 7 females, 32–51 years old, were recruited and randomly assigned to the traditional rehabilitation treatment group（PP group, n = 10） or the motor imagery training combined with traditional rehabilitation treatment group（MP group, n = 10）. All patients received rehabilitation training once a day, 45 minutes per session, five times per week, for 4 consecutive weeks. In the MP group, motor imagery training was performed for 45 minutes after traditional rehabilitation training, daily. Action Research Arm Test and the Fugl-Meyer Assessment of the upper extremity were used to evaluate hand functions before and after treatment. Transcranial magnetic stimulation was used to analyze motor evoked potentials in the affected extremity. Diffusion tensor imaging was used to assess changes in brain neural networks. Compared with the PP group, the MP group showed better recovery of hand function, higher amplitude of the motor evoked potential in the abductor pollicis brevis, greater fractional anisotropy of the right dorsal pathway, and an increase in the fractional anisotropy of the bilateral dorsal pathway. Our findings indicate that 4 weeks of motor imagery training combined with traditional rehabilitation treatment improves hand function in stroke patients by enhancing the dorsal pathway. This trial has been registered with the Chinese Clinical Trial Registry（registration number： Chi CTR-OCH-12002238）.

Acupuncture at Waiguan (TE5) influences activation/deactivation of functional brain areas in ischemic stroke patients and healthy people A functional MRI study

In the present study, 10 patients with ischemic stroke in the left hemisphere and six healthy controls were subjected to acupuncture at right Waiguan （TE5）. In ischemic stroke subjects, functional MRI showed enhanced activation in Broadmann areas 5, 6, 7, 18, 19, 24, 32, the hypothalamic inferior lobe, the mamiilary body, and the ventral posterolateral nucleus of the left hemisphere, and Broadmann areas 4, 6, 7, 18, 19 and 32 of the right hemisphere, but attenuated activation of Broadmann area 13, the hypothalamic inferior lobe, the posterior lobe of the tonsil of cerebellum, and the culmen of the anterior lobe of hypophysis, in the left hemisphere and Broadmann area 13 in the right hemisphere. In ischemic stroke subjects, a number of deactivated brain areas were enhanced, including Broadmann areas 6, 11,20, 22, 37, and 47, the culmen of the anterior lobe of hypophysis, alae lingulae cerebella, and the posterior lobe of the tonsil of cerebellum of the left hemisphere, and Broadmann areas 8, 37, 45 and 47, the culmen of the anterior lobe of hypophysis, pars tuberalis adenohypophyseos, inferior border of lentiform nucleus, lateral globus pallidus, inferior temporal gyrus, and the parahippocampal gyrus of the right hemisphere. These subjects also exhibited attenuation of a number of deactivated brain areas, including Broadmann area 7. These data suggest that acupuncture at Waiguan specifically alters brain function in regions associated with sensation, vision, and motion in ischemic stroke patients. By contrast, in normal individuals, acupuncture at Waiguan generally activates brain areas associated with insomnia and other functions.

Changes in brain activation in stroke patients after mental practice and physical exercise: a functional MRI study

Mental practice is a new rehabilitation method that reters to the mental rehearsal ot motor imagery content with the goal of improving motor performance. However, the relationship between activated regions and motor recovery after mental practice training is not well understood. In this study, 15 patients who suffered a firstever subcortical stroke with neurological deficits affecting the right hand, but no significant cognitive impairment were recruited. 10 patients underwent mental practice combined with physical practice training, and 5 patients only underwent physical practice training. We observed brain activation regions after 4 weeks of training, and explored the correlation of activation changes with functional recovery of the affected hands. The results showed that, after 4 weeks of mental practice combined with physical training, the Fugl-Meyer assessment score for the affected right hand was significantly increased than that after 4 weeks of practice training alone. Functional MRI showed enhanced activation in the left primary somatosensory cortex, attenuated activation intensity in the right primary motor cortex, and enhanced right cerebellar activation observed during the motor imagery task using the affected right hand after mental practice training. The changes in brain cortical activity were related to functional recovery of the hand. Experimental findings indicate that cortical and cerebellar functional reorganization following mental practice contributed to the improvement of hand function.

Regional brain structural abnormality in ischemic stroke patients:a voxel-based morphometry study

Our previous study used regional homogeneity analysis and found that activity in some brain areas of patients with ischemic stroke changed significantly. In the current study, we examined structural changes in these brain regions by taking structural magnetic resonance imaging scans of 11 ischemic stroke patients and 15 healthy participants, and analyzing the data using voxel-based morphometry. Compared with healthy participants, patients exhibited higher gray matter density in the left inferior occipital gyrus and right anterior white matter tract. In contrast, gray matter density in the right cerebellum, left precentral gyrus, right middle frontal gyrus, and left middle temporal gyrus was less in ischemic stroke patients. The changes of gray matter density in the middle frontal gyrus were negatively associated with the clin- ical rating scales of the Fugl-Meyer Motor Assessment （r = -0.609, P = 0.047） and the left middle temporal gyrus was negatively correlated with the clinical rating scales of the nervous functional deficiency scale （r = -0.737, P = 0.010）. Our findings call objectively identify the functional abnormality in some brain regions of ischemic stroke patients.

Limb remote ischemic postconditioning protects integrity of the blood-brain barrier after stroke

Integrity of the blood-brain barrier structure is essential for maintaining the internal environment of the brain.Development of cerebral infarction and brain edema is strongly associated with blood-brain barrier leakage.Therefore,studies have suggested that protecting the blood-brain barrier may be an effective method for treating acute stroke.To examine this possibility,stroke model rats were established by middle cerebral artery occlusion and reperfusion.Remote ischemic postconditioning was immediately induced by three cycles of 10-minute ischemia/10-minute reperfusion of bilateral hind limbs at the beginning of middle cerebral artery occlusion reperfusion.Neurological function of rat models was evaluated using Zea Longa’s method.Permeability of the blood-brain barrier was assessed by Evans blue leakage.Infarct volume and brain edema were evaluated using 2,3,5-triphenyltetrazolium chloride staining.Expression of matrix metalloproteinase-9 and claudin-5 m RNA was determined by real-time quantitative reverse transcription-polymerase chain reaction.Expression of matrix metalloproteinase-9 and claudin-5 protein was measured by western blot assay.The number of matrix metalloproteinase-9-and claudin-5-positive cells was analyzed using immunohistochemistry.Our results showed that remote ischemic postconditioning alleviated disruption of the blood-brain barrier,reduced infarct volume and edema,decreased expression of matrix metalloproteinase-9 m RNA and protein and the number of positive cells,increased expression of claudin-5 m RNA and protein and the number of positive cells,and remarkably improved neurological function.These findings confirm that by suppressing expression of matrix metalloproteinase-9 and claudin-5 induced by acute ischemia/reperfusion,remote ischemic postconditioning reduces blood-brain barrier injury,mitigates ischemic injury,and exerts protective effects on the brain.

Targeting brain microvascular endothelial cells: a therapeutic approach to neuroprotection against stroke

Brain microvascular endothelial cells form the interface between nervous tissue and circulating blood, and regulate central nervous system homeostasis. Brain microvascular endothelial cells differ from peripheral endothelial cells with regards expression of specific ion transporters and receptors, and contain fewer fenestrations and pinocytotic vesicles. Brain microvascular endothelial cells also synthesize several factors that influence blood vessel function. This review describes the morphological characteristics and functions of brain microvascular endothelial cells, and summarizes current knowledge regarding changes in brain microvascular endothelial cells during stroke progression and therapies. Future studies should focus on identifying mechanisms underlying such changes and developing possible neuroprotective therapeutic interventions.