Application of Time-Tracking Platform in the Reperfusion Treatment of Patients with Acute Ischemic Stroke in Primary Hospitals

Objective To explore the application effect of time tracking platform in improving the reperfusion treatment of patients with acute ischemic stroke in primary hospitals. Methods and Results Patients with acute ischemic stroke who carried out emergency intravenous thrombolysis and arterial thrombectomy in our hospital in 2021, 2022 and 2023 were selected. The time tracking mode was implemented, and the patients were recorded at each time node of the hospital and the whole-process digital management was conducted. Compared the mean DNT (Door to Needle Time) of intravenous thrombolysis in emergency stroke patients in 2021, 2022 and 2023, the total number of hospital cases within 4.5 h of onset, the total number of thrombolysis cases within 4.5 h of onset, the number of intravenous thrombolysis in 60 minutes of acute ischemic stroke, and the number of thrombolysis cases. The results show that from 2021 to 2023 our emergency stroke patients with intravenous thrombolysis average DNT shortened year by year, to the hospital within 4.5 h after the onset of the difference is statistically significant (all P < 0.05) conclusion through the application of stroke time tracking platform, is beneficial to shorten the treatment time of each link, can effectively reduce the hospital time delay, improve the rate of thrombolysis, improve the reperfusion of stroke centers in primary hospitals.

Vagus nerve stimulation in cerebral stroke:biological mechanisms,therapeutic modalities,clinical applications,and future directions

Stroke is a major disorder of the central nervous system that poses a serious threat to human life and quality of life.Many stro ke victims are left with long-term neurological dysfunction,which adversely affects the well-being of the individual and the broader socioeconomic impact.Currently,poststroke brain dysfunction is a major and difficult area of treatment.Vagus nerve stimulation is a Food and Drug Administration-approved exploratory treatment option for autis m,refractory depression,epilepsy,and Alzheimer’s disease.It is expected to be a novel therapeutic technique for the treatment of stroke owing to its association with multiple mechanisms such as alte ring neurotransmitters and the plasticity of central neuro ns.In animal models of acute ischemic stroke,vagus nerve stimulation has been shown to reduce infarct size,reduce post-stroke neurological damage,and improve learning and memory capacity in rats with stroke by reducing the inflammatory response,regulating bloodbrain barrier permeability,and promoting angiogenesis and neurogenesis.At present,vagus nerve stimulation includes both invasive and non-invasive vagus nerve stimulation.Clinical studies have found that invasive vagus nerve stimulation combined with rehabilitation therapy is effective in im proving upper limb motor and cognitive abilities in stroke patients.Further clinical studies have shown that non-invasive vagus nerve stimulation,including ear/ce rvical vagus nerve stimulation,can stimulate vagal projections to the central nervous system similarly to invasive vagus nerve stimulation and can have the same effect.In this paper,we first describe the multiple effects of vagus nerve stimulation in stroke,and then discuss in depth its neuroprotective mechanisms in ischemic stroke.We go on to outline the res ults of the current major clinical applications of invasive and non-invasive vagus nerve stimulation.Finally,we provide a more comprehensive evaluation of the advantages and disadvantages of different types of vagus nerve stimulation in the treatment of cerebral ischemia and provide an outlook on the developmental trends.We believe that vagus nerve stimulation,as an effective treatment for stroke,will be widely used in clinical practice to promote the recovery of stroke patients and reduce the incidence of disability.

Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery

Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic CEC-sEVs.In the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector.Small EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a control.Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs.An array of behavior assays was used to measure neurological function.Compared with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological outcomes.In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth.Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone.Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs.Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes.Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.

Drug-coated balloon angioplasty for the treatment of intracranial arterial stenosis in a young stroke patient:A case report

BACKGROUND Intracranial arterial narrowing is a significant factor leading to brief episodes of reduced blood flow to the brain,known as transient ischemic attacks,or fullblown strokes.While atherosclerosis is commonly associated with intracranial arterial narrowing,it is frequently of a non-atherosclerotic nature in younger patients.CASE SUMMARY Here,we present the case of a young stroke patient with narrowing of the middle cerebral artery(MCA),characterized as non-atherosclerotic lesions,who experienced an ischemic stroke despite receiving standard drug therapy.The patient underwent digital subtraction angiography(DSA)to assess the entire network of blood vessels in the brain,revealing significant narrowing(approximately 80%)in the M1 segment of the right MCA.Subsequently,the patient underwent Drug-Coated Balloon Angioplasty to treat the stenosis in the right MCA's M1 segment.Follow-up DSA confirmed the resolution of stenosis in this segment.Although the remaining branches showed satisfactory blood flow,the vessel wall exhibited irregularities.A review of DSA conducted six months later showed no evident stenosis in the right MCA,with a smooth vessel wall.CONCLUSION The use of drug-coated balloon angioplasty demonstrated favorable outcomes in repairing and reshaping the blood vessel wall in young patients.Therefore,it may be considered a promising treatment option for similar cases.

Treatment with β-sitosterol ameliorates the effects of cerebral ischemia/reperfusion injury by suppressing cholesterol overload, endoplasmic reticulum stress, and apoptosis

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.

Cav3.2 channel regulates cerebral ischemia/reperfusion injury:a promising target for intervention

Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion injury.Various calcium channels are involved in cerebral ischemia/reperfusion injury.Cav3.2 channel is a main subtype of T-type calcium channels.T-type calcium channel blockers,such as pimozide and mibefradil,have been shown to prevent cerebral ischemia/reperfusion injury-induced brain injury.However,the role of Cav3.2 channels in cerebral ischemia/reperfusion injury remains unclear.Here,in vitro and in vivo models of cerebral ischemia/reperfusion injury were established using middle cerebral artery occlusion in mice and high glucose hypoxia/reoxygenation exposure in primary hippocampal neurons.The results showed that Cav3.2 expression was significantly upregulated in injured hippocampal tissue and primary hippocampal neurons.We further established a Cav3.2 gene-knockout mouse model of cerebral ischemia/reperfusion injury.Cav3.2 knockout markedly reduced infarct volume and brain water content,and alleviated neurological dysfunction after cerebral ischemia/reperfusion injury.Additionally,Cav3.2 knockout attenuated cerebral ischemia/reperfusion injury-induced oxidative stress,inflammatory response,and neuronal apoptosis.In the hippocampus of Cav3.2-knockout mice,calcineurin overexpression offset the beneficial effect of Cav3.2 knockout after cerebral ischemia/reperfusion injury.These findings suggest that the neuroprotective function of Cav3.2 knockout is mediated by calcineurin/nuclear factor of activated T cells 3 signaling.Findings from this study suggest that Cav3.2 could be a promising target for treatment of cerebral ischemia/reperfusion injury.

The potential mechanism and clinical application value of remote ischemic conditioning in stroke

Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.

Application of multidisciplinary in situ simulation training in the treatment of acute ischemic stroke: a quality improvement project

BACKGROUND:Ischemic stroke refers to a disorder in the blood supply to a local area of brain tissue for various reasons and is characterized by high morbidity,mortality,and disability.Early reperfusion of brain tissue at risk of injury is crucial for the treatment of acute ischemic stroke.The purpose of this study was to evaluate comfort levels in managing acute stroke patients with hypoxemia who required endotracheal intubation after multidisciplinary in situ simulation training and to shorten the door-to-image time.METHODS:This quality improvement project utilized a comprehensive multidisciplinary in situ simulation exercise.A total of 53 participants completed the two-day in situ simulation training.The main outcome was the self-reported comfort levels of participants in managing acute stroke patients with hypoxemia requiring endotracheal intubation before and after simulation training.A 5-point Likert scale was used to measure participant comfort.A paired-sample t-test was used to compare the mean self-reported comfort scores of participants,as well as the endotracheal intubation time and door-to-image time on the fi rst and second days of in situ simulation training.The door-to-image time before and after the training was also recorded.RESULTS:The findings indicated that in situ simulation training could enhance participant comfort when managing acute stroke patients with hypoxemia who required endotracheal intubation and shorten door-to-image time.For the emergency management of hypoxemia or tracheal intubation,the mean post-training self-reported comfort score was signifi cantly higher than the mean pre-training comfort score(hypoxemia:4.53±0.64 vs.3.62±0.69,t=-11.046,P<0.001;tracheal intubation:3.98±0.72 vs.3.43±0.72,t=-6.940,P<0.001).We also observed a decrease in the tracheal intubation and door-to-image time and a decreasing trend in the door-to-image time,which continued after the training.CONCLUSION:Our study demonstrates that the implementation of in situ simulation training in a clinical environment with a multidisciplinary approach may improve the ability and confi dence of stroke team members,optimize the fi rst-aid process,and eff ectively shorten the door-to-image time of stroke patients with emergency complications.

A promising approach for quantifying focal stroke modeling and assessing stroke progression:optical resolution photoacoustic microscopy photothrombosis

To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex.However,these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied,although ischemic stroke is strongly age-related.In this study,we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed laser.We observed the molding process in mice of different ages and presented age-dependent vascular embolism differentiation.Moreover,we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a stroke.Our imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages,thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.

Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke

It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke.Indeed,previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue.Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke,but its specific role and mechanism are currently unclear.To simulate stroke in vivo,a middle cerebral artery occlusion rat model was established,with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke.We found that in the early stage(within 24 hours)of ischemic stroke,neutrophils produced a large amount of hypochlorous acid,while in the recovery phase(10 days after stroke),microglia were activated and produced a small amount of hypochlorous acid.Further,in acute stroke in rats,hypochlorous acid production was prevented using a hypochlorous acid scavenger,taurine,or myeloperoxidase inhibitor,4-aminobenzoic acid hydrazide.Our results showed that high levels of hypochlorous acid(200μM)induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation.However,in the recovery phase of the middle cerebral artery occlusion model,a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes.This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury.Lower levels of hypochlorous acid(5 and 100μM)promoted nuclear translocation ofβ-catenin.By transfection of single-site mutation plasmids,we found that hypochlorous acid induced chlorination of theβ-catenin tyrosine 30 residue,which promoted nuclear translocation.Altogether,our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

Isolated cerebral mucormycosis that looks like stroke and brain abscess:A case report and review of the literature

BACKGROUND Cerebral mucormycosis is an infectious disease of the brain caused by fungi of the order Mucorales.These infections are rarely encountered in clinical practice and are often misdiagnosed as cerebral infarction or brain abscess.Increased mortality due to cerebral mucormycosis is closely related to delayed diagnosis and treatment,both of which present unique challenges for clinicians.CASE SUMMARY Cerebral mucormycosis is generally secondary to sinus disease or other disseminated disease.However,in this retrospective study,we report and analyze a case of isolated cerebral mucormycosis.CONCLUSION The constellation of symptoms including headaches,fever,hemiplegia,and changes in mental status taken together with clinical findings of cerebral infarction and brain abscess should raise the possibility of a brain fungal infection.Early diagnosis and prompt initiation of antifungal therapy along with surgery can improve patient survival.

Whole-brain CT Perfusion at Admission and During Delayed Time-window Detects the Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage

Objective To evaluate the utility of computed tomography perfusion(CTP)both at admission and during delayed cerebral ischemia time-window(DCITW)in the detection of delayed cerebral ischemia(DCI)and the change in CTP parameters from admission to DCITW following aneurysmal subarachnoid hemorrhage.Methods Eighty patients underwent CTP at admission and during DCITW.The mean and extreme values of all CTP parameters at admission and during DCITW were compared between the DCI group and non-DCI group,and comparisons were also made between admission and DCITW within each group.The qualitative color-coded perfusion maps were recorded.Finally,the relationship between CTP parameters and DCI was assessed by receiver operating characteristic(ROC)analyses.Results With the exception of cerebral blood volume(P=0.295,admission;P=0.682,DCITW),there were significant differences in the mean quantitative CTP parameters between DCI and non-DCI patients both at admission and during DCITW.In the DCI group,the extreme parameters were significantly different between admission and DCITW.The DCI group also showed a deteriorative trend in the qualitative color-coded perfusion maps.For the detection of DCI,mean transit time to the center of the impulse response function(Tmax)at admission and mean time to start(TTS)during DCITW had the largest area under curve(AUC),0.698 and 0.789,respectively.Conclusion Whole-brain CTP can predict the occurrence of DCI at admission and diagnose DCI during DCITW.The extreme quantitative parameters and qualitative color-coded perfusion maps can better reflect the perfusion changes of patients with DCI from admission to DCITW.

Susceptibility gene for stroke or cerebral infarction in the Han population in Hunan Province of China

The scavenger receptor class B type I gene can protect against atherosclerosis; a mononucleotide polymorphism is associated with differences in blood lipid metabolism, postprandial serum lipid levels, insulin resistance, coronary artery disease and familial hyperlipidemia. In this study, the scavenger receptor class B type I gene exon 1 G4A gene polymorphism in atherosclerotic cerebral infarction patients, cerebral hemorrhage patients and normal controls was detected using the polymerase chain reaction-restriction fragment length polymorphism method. The results showed that the GA ＋ AA genotype frequency of scavenger receptor class B type I gene G4A in atherosclerotic cerebral infarction patients was similar to that in cerebral hemorrhage patients and normal controls; however, the A allele frequency was significantly lower than that in normal controls. The serum level of high-density lipoprotein cholesterol in patients with the scavenger receptor class B type I gene G4A GA ＋ AA genotype was significantly higher, while the serum level of low-density lipoprotein cholesterol was significantly lower than that in patients with the GG genotype, in both the atherosclerotic cerebral infarction and cerebral hemorrhage groups. The serum level of high-density lipoprotein cholesterol in patients with the scavenger receptor class B type I gene G4A GA ＋ AA genotype was significantly higher, while the serum levels of low-density lipoprotein cholesterol and total cholesterol were significantly lower than those in normal controls with the GG genotype. Our experimental results suggest that the G4A polymorphism of the scavenger receptor class B type I gene is a possible predisposing risk factor for atherosclerotic cerebral infarction, and that it has no association with cerebral hemorrhage in the Hart population in Hunan province of China. The A allele is possibly associated with the metabolism of high-density and low-density lipoprotein cholesterol.

Nanotechnology-based therapeutics: new hope for ischemic cerebral stroke intervention

Ischemic cerebral stroke is a leading cause of death and disability globally.At present,thrombolytics,such as recombinant tissue-type plasminogen activator,are the only effective treatment for acute stroke.However,usage of thrombolytics has a strict therapeutic window and cannot be applied to a number of patients.Despite the promising effects of some neuroprotectants in preclinical studies,they failed in clinical trials as a result of poor pharmacokinetic properties,particularly with regard to solubility and permeability across the blood-brain barrier(BBB).Approaches for delivering these drugs by nanotechnologies may overcome these pharmacokinetic deficits and enhance their neuroprotective effects.However,issues such as potential side effects and biosafety properties currently limit clinical application of these approaches.In this article,we reviewed recent progress of nanotechnology-based interventions for stroke treatment,and in particular,summarized novel materials applied to synthesize nanocarriers,encapsulation with neuroprotectants,and factors impacting nanodrug bioactivities to provide a theoretical basis for the development of anti-stroke drugs.

多模态磁共振成像联合estroke人工智能评估在晚时间窗急性脑梗死动脉取栓术的临床研究

目的分析多模态磁共振成像(MRI)联合estroke人工智能评估在晚时间窗急性脑梗死(AIS)动脉取栓术中的临床价值。方法选取2021年7月至2023年6月本院收治的104例晚时间窗AIS患者,所有患者经多模态MRI联合estroke人工智能评估后均可进行动脉取栓,根据eStroke人工智评估结果,将患者按照梗死体积分为低梗死组(梗死体积<21ml)、中等梗死组(21mL<梗死体积<31mL)及较大梗死组(31mL<梗死体积<51mL)。另同期选取于本院进行急诊取栓的时间窗内AIS患者30例,纳入对照组。术后采用改良脑梗死溶栓(mTICI)分级评估血管再通情况。统计患者取栓次数、下床活动时间及住院时间,统计患者住院期间并发症发生率。出院后所有患者均随访3个月,统计患者90 d死亡情况及脑卒中再发情况。采用改良Rankin量表(mRS)及美国国立卫生院神经功能缺损评分(NIHSS)评估患者神经功能预后。结果与低梗死组比,较大梗死组血管再通率降低(P<0.05),与较大梗死组比较,对照组血管再通率升高(P<0.05);与低梗死组比较,对照组血取栓次数增加(P<0.05);与低梗死组比较,对照组并发症发生率升高(P<0.05);与术前比较,4组患者术后3个月mRS评分、NIHSS评分均降低(P<0.05);与低梗死组比较,中等梗死组及较大梗死组mRS评分、NIHSS评分升高(P<0.05),与中等梗死组比较,较大梗死组mRS评分、NIHSS评分升高(P<0.05),与较大梗死组比较,对照组mRS评分、NIHSS评分降低(P<0.05),低梗死组与对照组比较,mRS评分、NIHSS评分差异无统计学意义(P>0.05)。结论多模态MRI联合estroke人工智能评估晚时间窗AIS动脉取栓术中具有良好的血管再通率,有利于减少取栓次级术后并发症的发生,对于神经功能改善具有积极作用。

Exosome-transported IncRNA H19 regulates insulin-like growth factor-1 via the H19/let-7a/insulin-like growth factor-1 receptor axis in ischemic stroke

LncRNA(long non-coding RNA) H19 is a transcript of the H19 gene that is expressed during embryogenesis.We previously discove red a role for circular lncRNA H19 in the onset and prognosis of cerebral ischemic stroke.In this study,we used serum from patients with ischemic stroke,and mouse and cell culture models to elucidate the roles of plasma and neuronal exosomes in the regulatory effect of lncRNA H19 on insulin-like growth factor-1 and its mechanism in ischemic stroke,using western blotting,quantitative real-time polymerase chain reaction,and enzyme-linked immunosorbent assays.Plasma exosomal IncRNA H19 was negatively associated with blood levels of insulin-like growth factor-1 in samples from patients with cerebral ischemic stroke.In a mouse model,levels of exosomal IncRNA H19 were positively correlated with plasma and cerebral lncRNA H19.In a cell co-culture model,we confirmed that IncRNA H19 was transported from neuro ns to astrocytes by exosomes to induce downregulation of insulin-like growth factor-1 through the H19/let-7 a/insulin-like growth factor-1 receptor axis.This study provides the first evidence for the transpo rtation of IncRNA H19 by exosomes and the relationship between IncRNA H19 and insulinlike growth factor-1.

Overexpression of vascular endothelial growth factor enhances the neuroprotective effects of bone marrow mesenchymal stem cell transplantation in ischemic stroke

Although bone marrow mesenchymal stem cells(BMSCs)might have therapeutic potency in ischemic stroke,the benefits are limited.The current study investigated the effects of BMSCs engineered to overexpress vascular endothelial growth factor(VEGF)on behavioral defects in a rat model of transient cerebral ischemia,which was induced by middle cerebral artery occlusion.VEGF-BMSCs or control grafts were injected into the left striatum of the infarcted hemisphere 24 hours after stroke.We found that compared with the stroke-only group and the vehicle-and BMSCs-control groups,the VEGF-BMSCs treated animals displayed the largest benefits,as evidenced by attenuated behavioral defects and smaller infarct volume 7 days after stroke.Additionally,VEGF-BMSCs greatly inhibited destruction of the blood-brain barrier,increased the regeneration of blood vessels in the region of ischemic penumbra,and reducedneuronal degeneration surrounding the infarct core.Further mechanistic studies showed that among all transplant groups,VEGF-BMSCs transplantation induced the highest level of brain-derived neurotrophic factor.These results suggest that BMSCs transplantation with vascular endothelial growth factor has the potential to treat ischemic stroke with better results than are currently available.

Pharmacodynamic evaluation of Cordyceps sinensis (Berk.) Sacc. for ischemic stroke in rats and potential mechanism through network pharmacology and molecular docking

Objective:To explore the therapeutic potential of Cordyceps sinensis(Berk.)Sacc.(C.sinensis,Dong Chong Xia Cao)in an ischemic stroke(IS)model and predict its possible mechanism through network pharmacology.Methods:Thirty-three SpragueeDawley rats were randomly divided into the Sham,model,and C.sinensis groups.After 5 days of pre-treatment,the model group and the C.sinensis group were sub-jected to middle cerebral artery occlusion(MCAO)modeling.Effect of C.sinensis on MCAO rats was evaluated by comparing cerebral infarct size,neurological function,cerebral water content,pathological changes,and certain biochemical indicators.Intersection targets between C.sinensis and IS was screened using network pharmacology analysis.Relationship among core components,targets and pathways of C.sinensis in treating IS was constructed through network pharmacology analysis and further verified by molecular docking.Finally,the DAVID v8.8 database was used for performing GO analysis and KEGG pathway enrichment analysis by importing the intersection targets.Results:Compared with the model group,C.sinensis significantly reduced the volume of cerebral infarction(P=0.026),the cerebral water content(P¼.0013),the mNSS score(P<0.001),and the levels of IL-17(P=0.031),TNF-α(P=0.016),MDA(P=0.014),and glutamate(P=0.014)in serum,while upregulating the level of SOD in serum and improving the pathological morphology in MCAO rat ischemic brains.The results of network pharmacology analysis showed that core targets(such as CASP3,PTGS2,and PPARG)and the main enrichment pathways(IL-17,AGE-RAGE,and TNF signaling pathways)were regulated by 30 chemical components of C.sinensis,which effectively treated IS in MCAO rats.Conclusion:The results of this study showed that C.sinensis effectively interfered with MCAO rats,and the mechanism may be related to the regulation of blood lipids and to anti-apoptosis and anti-inflammatory effects.

Neuroprotective Potential of Cerium Oxide Nanoparticles for Focal Cerebral Ischemic Stroke

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.

Therapeutic window of Qingkailing injection for focal cerebral ischemia/reperfusion injury

The time window in which a drug is effective varies between drugs. The present study investigated the therapeutic window of Qingkailing injection for focal cerebral ischemia/reperfusion in mice. Animals underwent middle cerebral artery occlusion and were injected with Qingkailing （1.5, 3, 6 mL/kg）. Infarct volume and neurological function were assessed after 24 hours of ischemia. In addition, to establish the therapeutic time window, mice were injected with 3 mL/kg Qingkailing at 0, 1, 3, 4, 6, 9 and 12 hours after occlusion. Results revealed that Qingkailing injection significantly reduced infarct volume and improved neurological function in model mice after cerebral infarction for up to 9 hours, demonstrating that the therapeutic window of Qingkailing injection can extend to 9 hours for cerebral ischemia/reperfusion in mice.