Relationship between ultrasound parameters of the umbilical and middle cerebral arteries and intrauterine fetal distress

BACKGROUND By comprehensively analyzing the blood flow parameters of the umbilical and middle cerebral arteries,doctors can more accurately identify fetal intrauterine distress,as well as assess its severity,so that timely interventions can be implemented to safeguard the health and safety of the fetus.AIM To identify the relationship between ultrasound parameters of the umbilical and middle cerebral arteries and intrauterine distress.METHODS Clinical data of pregnant women admitted between January 2021 and January 2023 were collected and divided into the observation and control groups(n=50 each),according to the presence or absence of intrauterine distress.The ultrasound hemodynamic parameters of the uterine artery(UtA),fetal middle cerebral artery(MCA),and umbilical artery(UmA)were compared with neonatal outcomes and occurrence of intrauterine distress in the two groups.RESULTS Comparison of ultrasonic hemodynamic parameters,resistance index(RI),pulsatility index(PI),and systolic maximal blood flow velocity of UmA compared to diastolic blood flow velocity(S/D),revealed higher values of fetal MCA,PI,and S/D of UmA in pregnant women with UtA compared to controls(P<0.05),while there was no difference between the two groups in terms of RI(P<0.05)The incidence of a neonatal Apgar score of 8-10 points was lower in the observation group(66.7%)than in the control group(90.0%),and neonatal weight(2675.5±27.6 g)was lower than in the control group(3117.5±31.2 g).Further,cesarean section rate was higher in the observation group(70.0%)than in the control group(11.7%),and preterm labor rate was higher in the observation group(40.0%)than in the control group(10.0%).The incidence of fetal distress,neonatal growth restriction and neonatal asphyxia were also higher in the observation group(all P<0.05).CONCLUSION Fetal MCA,UmA,and maternal UtA hemodynamic abnormalities all develop in pregnant women with intrauterine distress during late pregnancy,which suggests that clinical attention should be paid to them,and monitoring should be strengthened to provide guidance for clinical intervention.

Mimicking aneurysm in a patient with chronic occlusion of the left middle cerebral artery

The chronic occlusion of intracranial arteries generally has no or mild clinical symptoms,and the clinical symptoms of acute cerebral artery occlusion are mostly manifested as severe cerebral infarction symptoms,which often make early diagnosis difficult,thus losing the best treatment opportunity.Once cerebral infarction occurs,the consequences are difficult to recover.This is also an important reason for the high misdiagnosis rate and mortality of this disease.In this paper,the characteristics of the disease were analyzed to provide clinical reference.

Cerebral arterial blood flow,attention,and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage

BACKGROUND Intracerebral hemorrhage mainly occurs in middle-aged and elderly patients with hypertension,and surgery is currently the main treatment for hypertensive cerebral hemorrhage,but the bleeding caused by surgery will cause damage to the patient's nerve cells,resulting in cognitive and motor dysfunction,resulting in a decline in the patient's quality of life.AIM To investigate associations between cerebral arterial blood flow and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage.METHODS Eighty-nine patients with depression after acute hypertensive cerebral hemorrhage who were admitted to our hospital between January 2019 and July 2021 were selected as the observation group,while 100 patients without depression who had acute hypertensive cerebral hemorrhage were selected as the control group.The attention span of the patients was assessed using the Paddle Pin Test while executive function was assessed using the Wisconsin Card Sorting Test(WCST)and cognitive function was assessed using the Montreal Cognitive Assessment Scale(MoCA).The Hamilton Depression Rating Scale(HAMD-24)was used to evaluate the severity of depression of involved patients.Cerebral arterial blood flow was measured in both groups.RESULTS The MoCA score,net scores I,II,III,IV,and the total net score of the scratch test in the observation group were significantly lower than those in the control group(P<0.05).Concurrently,the total number of responses,number of incorrect responses,number of persistent errors,and number of completed responses of the first classification in the WCST test were significantly higher in the observation group than those in the control group(P<0.05).Blood flow in the basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery was significantly lower in the observation group than in the control group(P<0.05).The basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery were positively correlated with the net and total net scores of each part of the Paddle Pin test and the MoCA score(P<0.05),and negatively correlated with each part of the WCST test(P<0.05).In the observation group,the post-treatment improvement was more prominent in the Paddle Pin test,WCST test,HAMD-24 score,and MoCA score compared with those in the pre-treatment period(P<0.05).Blood flow in the basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery significantly improved in the observation group after treatment(P<0.05).CONCLUSION Impaired attention,and executive and cognitive functions are correlated with cerebral artery blood flow in patients with depression after acute hypertensive cerebral hemorrhage and warrant further study.

Regional dynamic cerebral autoregulation across anterior and posterior circulatory territories:A detailed exploration and its clinical implications

Cerebral autoregulation(CA)is the mechanism that maintains stable cerebral blood flow(CBF)despite fluctuations in systemic blood pressure,crucial for brain homeostasis.Recent evidence highlights distinct regional variations in CA between the anterior(carotid)and posterior(vertebrobasilar)circulations.Noninvasive neuromonitoring techniques,such as transcranial Doppler,transfer function analysis,and near-infrared spectroscopy,facilitate the dynamic assessment of CBF and autoregulation.Studies indicate a robust autoregulatory capacity in the anterior circulation,characterized by rapid adjustments in vascular resistance.On the contrary,the posterior circulation,mainly supplied by the vertebral arteries,may have a lower autoregulatory capacity.in acute brain injuries such as intracerebral and subarachnoid hemorrhage,and traumatic brain injuries,dynamic CA can be significantly altered in the posterior circulation.Proposed physiological mechanisms of impaired CA in the posterior circulation include:(1)Decreased sympathetic innervation of the vasculature impairing compensatory vasoreactivity;(2)Endothelial dysfunction;(3)Increased cerebral metabolic rate of oxygen consumption within the visual cortex causing CBFmetabolism(i.e.,neurovascular)uncoupling;and(4)Impaired blood-brain barrier integrity leading to impaired astrocytic mediated release of vasoactive substances(e.g.nitric oxide,potassium,and calcium ions).Furthermore,more research is needed on the effects of collateral circulation,as well as the circle of Willis variants,such as the fetal-type posterior cerebral artery,on dynamic CA.Improving our understanding of these mechanisms is crucial to improving the diagnosis,prognosis,and management of various cerebrovascular disorders.

Investigation multi-target synergistic mechanism of Choerospondias axillaris in the treat of cerebral ischemia based on systems pharmacology and experimental verification

Background:Choerospondias axillaris(CA)is a traditional Mongolian medicine that has been proven to have a good therapeutic effect on cerebrovascular disease.Cerebral Ischemia(CI)is a severe and life-threatening cerebrovascular disease.However,the specific mechanism of action of CA in the treatment of CI is still unclear.Methods:In this study,the related targets and pathways of CA in the treatment of CI were first predicted by system pharmacology and then verified by relevant experiments.Results:The results showed that 12 active ingredients and 208 targets were selected.Further validation through protein-protein interaction(PPI)network analysis and active ingredients-target-pathway(A-T-P)network analysis has confirmed the pivotal roles of the main bioactive constituents,including quercetin,kaempferol,naringin,β-sitosterol,and gallic acid.These components exert their anti-ischemic effects by modulating key targets such as IL6,TNF,MAPK3,and CASP3,thereby regulating the PI3K-Akt,HIF-1,and MAPK signaling pathways,which are integral to processes like inflammation,apoptosis,and oxidative stress.More importantly,through experimental verification,this study confirmed our prediction that CAE significantly reduced neurological function scores,infarct volume,and the percentage of apoptosis neurons.Conclusion:This indicates that CA acts on CI through multi-target synergistic mechanism,and this study provides theoretical basis for the clinical application of CA.

Exercise preconditioning alleviates ischemia-induced memory deficits by increasing circulating adiponectin

Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after stroke.In this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia.We also examined the role of exercise-induced circulating factors in these effects.Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion.We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory function.Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise.Agonist activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise effects.In summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.

Protective Effect of Tetrandrine and Fructose-1,6-diphos phate on the Model of Focal Cerebral Ischemia in Rats

The effect of tetrandrine (Tet) on the infarction area and volume of rat brain induced by middle cerebral artery occlusion (MCAO) was investigated. The treatment with Tet 7.5, 12.0 or 15.0 mg·kg 1 , or with fructose 1,6 diphosphate (FDP) 200 and 350 mg·kg 1 ip immediately after MCAO, respectively, significantly reduced the infarction area and volume in a dose dependent manner. MK801 and FDP also displayed a protective effect on brain ischemia. A combination of Tet and FDP administered immediately after MCAO, produced a more potent protective effect than those treated with Tet or FDP alone. When Tet or FDP was administered 1 h and 2 h after MCAO, respectively, they could still significantly reduce the infarction area and volume of brain tissue. But, there was no significant protective effect when these two compounds were given 3 h after MCAO.

Puerarin protects brain tissue against cerebral ischemia/reperfusion injury by inhibiting the inflammatory response

Puerarin, a traditional Chinese medicine, exerts a powerful neuroprotective effect in cerebral ischemia/reperfusion injury, but its mechanism is unknown. Here, we established rat models of middle cerebral artery ischemia/reperfusion injury using the suture method. Puerarin （100 mg/kg） was administered intraperitoneally 30 minutes before middle cerebral artery occlusion and 8 hours after reperfusion. Twenty-four hours after reperfusion, we found that puerarin significantly improved neurological deficit, reduced infarct size and brain water content, and notably diminished the expression of Toll-like receptor-4, myeloid differentiation factor 88, nuclear factor kappa B and tumor necrosis factor-α in the ischemic region. These data indicate that puerarin exerts an anti-inflammatory protective effect on brain tissue with ischemia/reperfusion damage by downregulating the expression of multiple inflammatory factors.

Do pyroptosis, apoptosis, and necroptosis (PANoptosis) exist in cerebral ischemia? Evidence from cell and rodent studies

Some scholars have recently developed the concept of PANoptosis in the study of infectious diseases where pyroptosis,apoptosis and necroptosis act in consort in a multimeric protein complex,PANoptosome.This allows all the components of PANoptosis to be regulated simultaneously.PANoptosis provides a new way to study the regulation of cell death,in that different types of cell death may be regulated at the same time.To test whether PANoptosis exists in diseases other than infectious diseases,we chose cerebral ischemia/reperfusion injury as the research model,collected articles researching cerebral ischemia/reperfusion from three major databases,obtained the original research data from these articles by bibliometrics,data mining and other methods,then integrated and analyzed these data.We selected papers that investigated at least two of the components of PANoptosis to check its occurrence in ischemia/reperfusion.In the cell model simulating ischemic brain injury,pyroptosis,apoptosis and necroptosis occur together and this phenomenon exists widely in different passage cell lines or primary neurons.Pyroptosis,apoptosis and necroptosis also occurred in rat and mouse models of ischemia/reperfusion injury.This confirms that PANoptosis is observed in ischemic brain injury and indicates that PANoptosis can be a target in the regulation of various central nervous system diseases.

Inflammatory response and neuronal necrosis in rats with cerebral ischemia

In the middle cerebral artery occlusion model of ischemic injury, inflammation primarily occurs in the infarct and peripheral zones. In the ischemic zone, neurons undergo necrosis and apoptosis, and a large number of reactive microglia are present. In the present study, we investigated the pathological changes in a rat model of middle cerebral artery occlusion. Neuronal necrosis appeared 12 hours after middle cerebral artery occlusion, and the peak of neuronal apoptosis ap- peared 4 to 6 days after middle cerebral artery occlusion. Inflammatory cytokines and microglia play a role in damage and repair after middle cerebral artery occlusion. Serum intercellular cell adhesion molecule-1 levels were positively correlated with the permeability of the blood-brain barrier. These findings indicate that intercellular cell adhesion molecule-1 may be involved in blood-brain barrier injury, microglial activation, and neuronal apoptosis. Inhibiting blood-brain barrier leakage may alleviate neuronal injury following ischemia,

Therapeutic effects of different durations of acupuncture on rats with middle cerebral artery occlusion

Acupuncture is regarded as an effective therapy for cerebral ischemia. Different acupuncture ma- nipulations and durations may result in different therapeutic effects. In the present study, the Neig uan （PC6） acupoint of rats with occluded middle cerebral arteries was needled at a fixed frequency （3 Hz） with different durations, i.e., 5, 60 and 180 seconds under a twisting-rotating acupuncture method. Results showed that different durations of acupuncture had different therapeutic effects, with 60 seconds yielding a better therapeutic effect than the other two groups. This duration of treatment demonstrated rapid cerebral blood flow, encouraging recovery of neurological function, and small cerebral infarct volume. Experimental findings indicated that under 3 Hz frequency, the treatment of needling Neiguan for 60 seconds is effective for ischemic stroke.

Influence of Ren and Du meridian electro-acupuncture on neural stem cell proliferation and extracellular signal-regulated kinase pathway in a rat model of focal cerebral ischemia injury

BACKGROUND： Studies have shown that electro-acupuncture at the Ren meridian could improve proliferation of subventricular zone neural stem cells in cerebral-ischemic rats. However, there are few reports on the influence of electro-acupuncture at the Du meridian on neural stem cell proliferation. OBJECTIVE： To observe the influence of electro-acupuncture at Ren and Du meridians on neural stem cell proliferation in the subventricular zone and altered signal transduction in cerebral ischemia rats. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of Human Anatomy, Medical College of Sun Yat-sen University from May 2006 to February 2008. MATERIALS： Mouse anti-rat bromodeoxyuridine （BrdU） monoclonal antibody was provided by Sigma, USA; mouse anti-rat nestin monoclonal antibody and extracellular signal-regulated protein kinase （ERK） specific inhibitor PD98059 were provided by Calbiochem, Germany; acupuncture needle was provided by Suzhou Acupuncture Supplies, China. METHODS： A total of 126 rats were randomly assigned to four groups： model （n = 36）, Du meridian （n = 36）, Ren/Du meridian （n = 36）, and Ren/Du meridian ＋ PD98059 （n = 18）. Rats in the Ren/Du meridian ＋ PD98059 group were observed on days 7 （n = 6） and 14 （n = 12） after cerebral ischemia injury. Rats in the model, Du meridian, and Ren/Du meridian groups were observed on days 7, 14, and 28 after cerebral ischemia injury, with 12 rats per group at each time point. Thread occlusion was used to establish middle cerebral artery occlusion models. Electro-acupuncture was performed at Renzhong （DU 26） and Baihui （DU 20） acupoints in the Du meridian group, as well as Chengjiang （RN 24）, Guanyuan （RN 4）, Renzhong, and Baihuiacupoints in the Ren/Du meridian and Ren/Du meridian ＋ PD98059 groups 2 days after model establishment. In addition, electro-acupuncture stimulation with disperse-dense waves was performed, with 30 Hz disperse wave, 100 Hz dense wave, and 5 V intensity for 20 minutes. Rats in the Ren/Du meridian ＋ PD98059 group were treated with 0.2 pg PD98059 injection into the subventricular zone, 2 pL per rat. Rats in the model group were not treated with electro-acupuncture. MAIN OUTCOME MEASURES： BrdU/nestin immunofluorescent staining was used to detect proliferating neural stem cells in the subventricular zone of cerebral ischemia rats; Western blot was used to determine phosphorylated ERK1 and 2 （pERK1/2） expression in the subventricular zone. RESULTS： On days 14 and 28 after cerebral ischemia, there were significantly more BrdU-positive and BrdU/nestin-positive cells in the Ren/Du meridian group compared with the Du meridian group （P 〈 0.05）. PD98059 decreased the number of BrdU-positive and BrdU/nestin-positive cells induced by electro-acupuncture at the/：ten and Du meridians （P 〈 0.05）. On days 7, 14, and 28 after treatment, pERK1/2 expression was significantly greater in the Du meridian and Ren/Du meridian groups compared with the model group （P 〈 0.05）. The promoting effect of electro-acupuncture at Ren and Du meridians on ERK1/2 phosphorylation was superior to electro-acupuncture at the Du meridian alone on day 14 after model induction （P 〈 0.05）. However, PD98059 completely abolished the promoting effect of electro-acupuncture at Ren/Du meridians on pERK1/2 expression （P 〈 0.05）. CONCLUSION： Electro-acupuncture at Ren and Du meridians increased proliferation of subventricular zone neural stem cells, which was related to activation of the ERK pathway in a rat model of cerebral ischemia injury.

Comparison of the anti-apoptotic effects of 15-and 35-minute suspended moxibustion after focal cerebral ischemia/reperfusion injury

Heat-sensitive suspended moxibustion has a neuroprotective effect against focal cerebral ischemia/reperfusion injury, but the underly- ing mechanisms remain unclear. The duration of heat-sensitive suspended moxibustion （usually from 30 minutes to 1 hour） is longer than traditional suspended moxibustion （usually 15 minutes）. However, the effects of 15- and 35-minute suspended moxibustion in rats with cerebra/ischemia/reperfusion injury are poorly understood. In this study, we performed 15- or 35-minute suspended moxibustion at acupoint Dazhui （GV14） in an adult rat model of focal cerebral ischemia/reperfusion injury. Infarct volume was evaluated with the 2,3,5-triphenyltetrazolium chloride assay. Histopathological changes and neuronal apoptosis at the injury site were assessed by hematoxy- lin-eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Caspase-9 and caspase-3 expression at the in- jury site was detected using immunofluorescent staining. Bax and Bcl-2 expression at the injury site was assessed using western blot assay. In the 35-minute moxibustion group, infarct volume was decreased, neuronal apoptosis was reduced, caspase-9, caspase-3 and Bax expres- sion was lower, and Bcl-2 expression was increased, compared with the 15-minute moxibustion group. Our findings show that 35-minute moxibustion has a greater anti-apoptotic effect than 15-minute moxibustion after focal cerebral ischemia/reperfusion injury.

Neuroprotective effect of penehyclidine hydrochloride on focal cerebral ischemia-reperfusion injury

Penehyclidine hydrochloride can promote microcirculation and reduce vascular permeability. However, the role of penehyclidine hydrochlodde in cerebral ischemia-reperfusion injury remains unclear. In this study, in vivo middle cerebral artery occlusion models were established in experimental rats, and penehyclidine hydrochloride pretreatment was given via intravenous injection prior to model establishment. Tetrazolium chloride, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling and immunohistochemical staining showed that, penehyclidine hydrochloride pretreatment markedly attenuated neuronal histopathological changes in the cortex, hippocampus and striatum, reduced infarction size, increased the expression level of BcI-2, decreased the expression level of caspase-3, and inhibited neuronal apoptosis in rats with cerebral ischemia-reperfusion injury. Xanthine oxidase and thiobarbituric acid chromogenic results showed that penehyclidine hydrochloride upregulated the activity of superoxide dismutase and downregulated the concentration of malondialdehyde in the ischemic cerebral cortex and hippocampus, as well as reduced the concentration of extracellular excitatory amino acids in rats with cerebral ischemia-reperfusion injury. In addition, penehyclidine hydrochloride inhibited the expression level of the NR1 subunit in hippocampal nerve cells in vitro following oxygen-glucose deprivation, as detected by PCR. Experimental findings indicate that penehyclidine hydrochloride attenuates neuronal apoptosis and oxidative stress injury after focal cerebral ischemia-reperfusion, thus exerting a neuroprotective effect.

Predictors of short-term outcome in patients with acute middle cerebral artery occlusion: unsuitability of fluid-attenuated inversion recovery vascular hyperintensity scores

Fluid-attenuated inversion recovery （FLAIR） vascular hyperintensity （FVH） is used to assess leptomeningeal collateral circulation, but clinical outcomes of patients with FVH can be very different. The aim of the present study was to assess a FVH score and explore its relationship with clinical outcomes. Patients with acute ischemic stroke due to middle cerebral artery M1 occlusion underwent magnetic resonance imaging and were followed up at 10 days （National Institutes of Health Stroke Scale） and 90 days （modified Rankin Scale） to determine short-term clinical outcomes. Effective collateral circulation indirectly improved recovery of neurological function and short-term clinical outcome by extending the size of the pial penumbra and reducing infarct lesions. FVH score showed no correlation with 90-day functional clinical outcome and was not sufficient as an independent predictor of short-term clinical outcome.

An enriched environment increases the expression of fibronectin type Ⅲ domain-containing protein 5 and brain-derived neurotrophic factor in the cerebral cortex of the ischemic mouse brain

Many studies have shown that fibronectin type III domain-containing protein 5(FDNC5) and brain-derived neurotrophic factor(BDNF) play vital roles in plasticity after brain injury. An enriched environment refers to an environment that provides animals with multi-sensory stimulation and movement opportunities. An enriched environment has been shown to promote the regeneration of nerve cells, synapses, and blood vessels in the animal brain after cerebral ischemia;however, the exact mechanisms have not been clarified. This study aimed to determine whether an enriched environment could improve neurobehavioral functions after the experimental inducement of cerebral ischemia and whether neurobehavioral outcomes were associated with the expression of FDNC5 and BDNF. This study established ischemic mouse models using permanent middle cerebral artery occlusion(pMCAO) on the left side. On postoperative day 1, the mice were randomly assigned to either enriched environment or standard housing condition groups. Mice in the standard housing condition group were housed and fed under standard conditions. Mice in the enriched environment group were housed in a large cage, containing various toys, and fed with a standard diet. Sham-operated mice received the same procedure, but without artery occlusion, and were housed and fed under standard conditions. On postoperative days 7 and 14, a beam-walking test was used to assess coordination, balance, and spatial learning. On postoperative days 16–20, a Morris water maze test was used to assess spatial learning and memory. On postoperative day 15, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex were analyzed by western blot assay. The results showed that compared with the standard housing condition group, the motor balance and coordination functions(based on beam-walking test scores 7 and 14 days after operation), spatial learning abilities(based on the spatial learning scores from the Morris water maze test 16–19 days after operation), and memory abilities(based on the memory scores of the Morris water maze test 20 days after operation) of the enriched environment group improved significantly. In addition, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex increased in the enriched environment group compared with those in the standard housing condition group. Furthermore, the Pearson correlation coefficient showed that neurobehavioral functions were positively associated with the expression levels of FDNC5 and BDNF(r = 0.587 and r = 0.840, respectively). These findings suggest that an enriched environment upregulates FDNC5 protein expression in the ipsilateral cerebral cortex after cerebral ischemia, which then activates BDNF protein expression, improving neurological function. BDNF protein expression was positively correlated with improved neurological function. The experimental protocols were approved by the Institutional Animal Care and Use Committee of Fudan University, China(approval Nos. 20160858 A232, 20160860 A234) on February 24, 2016.

Changes in synapse quantity and growth associated protein 43 expression in the motor cortex of focal cerebral ischemic rats following catalpol treatment

The present study investigated the effects of catalpol, the main constituent of the Chinese herb Rehmannia root, on neurons following brain ischemia, A rat model of focal permanent brain ischemia was established using electrocoagulation, The rats were intrapedtoneally injected with catalpol, at a dose of 5 mg/kg, daily for 1 week, Results showed that the number of neuronal synapses in the motor cortex and growth associated protein 43 expression were increased following catalpol treatment, indicating that catalpol might contribute to neuroplasticity and ameliorate functional neurological deficits induced by cerebral ischemia.

INTRANASAL DELIVERY OF NERVE GROWTH FACTOR TO PROTECT THE CENTRAL NERVOUS SYSTEM AGAINST ACUTE CEREBRAL INFARCTION

Objective To confirmed reliability and feasibility of intranasal nerve growth factor (NGF) bypassing the blood-brain barrier and its potential neuroprotective effects on acute cerebral ischemia. Methods (1) To assay NGF concentrations in different brain regions after middle cerebral artery occlusion (MCAO).Rats were randomly divided into intranasal (IN) NGF, intravenous (IV) NGF, and untreated group (n= 4). The concentra-tions of NGF of different brain regions in the three groups after MCAO were measured by ELISA. (2) To observe neuro-protective action of NGF on focal cerebral ischemic damage. Rats were randomly assigned to 4 groups: IN vehicle, IN NGF, IV vehicle, IV NGF (n= 8). Treatment was initiated 30 minutes after onset of MCAO and given again 24 hours later. Three neurologic behavioral tests were performed 24 and 48 hours following onset of MCAO. Corrected infarct volumes were determined 48 hours after onset of MCAO. Results The olfactory bulb in IN NGF group obtained the highest concentration (3252 pg/g) of NGF among all regions, followed by the hippocampus. The NGF concentrations in the olfactory bulb and hippocampus in IN NGF group were markedly higher than that in IV NGF and control groups. The infarct volume in IN NGF group was markedly reduced by 38.8% compared with IN vehicle group. IN NGF group vestibulum function markedly improved compared with IN vehicle group at 24 and 48 hours after onset of MCAO (P 24 h = 0.02 and P 48 h = 0.04, respectively). Conclusion Intranasal NGF could pass through the blood-brain barrier, reach the central nervous system, reduce infarct volume, and improve neurologic function in rats following MCAO. Intranasal delivery of NGF may be a promising treat-ment for stroke.

Ginkgolide B promotes the proliferation and differentiation of neural stem cells following cerebral ischemia/reperfusion injury,both in vivo and in vitro

Neural stem cells have great potential for the development of novel therapies for nervous system diseases.However,the proliferation of endogenous neural stem cells following brain ischemia is insufficient for central nervous system self-repair.Ginkgolide B has a robust neuroprotective effect.In this study,we investigated the cell and molecular mechanisms underlying the neuroprotective effect of ginkgolide B on focal cerebral ischemia/reperfusion injury in vitro and in vivo.Neural stem cells were treated with 20,40 and 60 mg/L ginkgolide B in vitro.Immunofluorescence staining was used to assess cellular expression of neuron-specific enolase,glial fibrillary acid protein and suppressor of cytokine signaling 2.After treatment with 40 and 60 mg/L ginkgolide B,cells were large,with long processes.Moreover,the proportions of neuron-specific enolase-,glial fibrillary acid protein-and suppressor of cytokine signaling 2-positive cells increased.A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion.Six hours after ischemia,ginkgolide B（20 mg/kg） was intraperitoneally injected,once a day.Zea Longa＇s method was used to assess neurological function.Immunohistochemistry was performed to evaluate the proportion of nestin-,neuron-specific enolase-and glial fibrillary acid protein-positive cells.Real-time quantitative polymerase chain reaction was used to measure m RNA expression of brain-derived neurotrophic factor and epidermal growth factor.Western blot assay was used to analyze the expression levels of brain-derived neurotrophic factor and suppressor of cytokine signaling 2.Ginkgolide B decreased the neurological deficit score,increased the proportion of nestin-,neuron-specific enolase-and glial fibrillary acid protein-positive cells,increased the m RNA expression of brain-derived neurotrophic factor and epidermal growth factor,and increased the expression levels of brain-derived neurotrophic factor and suppressor of cytokine signaling 2 in the ischemic penumbra.Together,the in vivo and in vitro findings suggest that ginkgolide B improves neurological function by promoting the proliferation and differentiation of neural stem cells in rats with cerebral ischemia/reperfusion injury.

Effect of Electroacupuncture on Neurological Deficit and Activity of Clock and Bmal1 in Cerebral Ischemic Rats

Acute focal cerebral ischemic stroke(IS)is a leading cause of morbidity and mortality worldwide.Acupuncture is an emerging alternative therapy that has been beneficial to acute brain ischemia.However,the underlying protective mechanism of its neuroprotective effect remains unclear.Human original circadian rhythm will be lost after IS,which seriously affects the quality of life and functional recovery of stroke patients.We hypothesize that acupuncture treats IS by regulating the balance of Clock and Bmal1.This study aims to explore the effect of acupuncture at acupoints GV20 and BL23 on neuroprotection and anti-apoptosis in middle cerebral artery occlusion(MCAO)rats and expression of apoptosis and circadian rhythm related proteins.Male Sprague-Dawley(SD)rats were randomly divided into five groups:normal group(Normal),sham model group(Sham MCAO),MCAO model group(MCAO),sham electroacupuncture group(Sham EA)and electroacupuncture group(EA).The MCAO model was prepared by electrocoagulation.The first acupuncture treatment was performed within 2 h after surgery,and then acupuncture therapy was performed on 1st day,2nd day and 3rd day respectively.After their neurological examination at 72 h of ischemia,the rats from each group were sacrificed.Triphenyltetrazolium chloride(TTC)staining was used to evaluate the brain infarct size.Ultrastructural observation on cerebral ischemic cortex and serum inflammatory cytokines were evaluated.TUNEL staining was used to detect cell apoptosis of brain tissue.The expression levels of proteins Bax,bcl-2,caspase-3,Clock and Bmal1 in the cerebral ischemic region were detected by immunofluorescence staining.Here,we presented evidence that EA at GV20 and BL23 could significantly improve the neurological deficit score and infarct size,and alleviate the cell apoptosis of brain tissue.Moreover,acupuncture treatment upregulated the anti-apoptotic Bcl-2/Bax ratio and reversed the upregulation of caspase-3 following 72-h cerebral ischemia.In addition,the expression levels of circadian proteins Clock and Bmal1 were upregulated in EA group while compared with MCAO group.Our study demonstrated that acupuncture exerted neuroprotective effect against neuronal apoptosis after stroke and the mechanism might be related with regulation of circadian rhythm proteins Clock and Bmal1.