Role In Stroke Research Articles

P6069Age-dependent platelet changes and their putative role for stroke in a mouse model of aging

P6069Age-dependent platelet changes and their putative role for stroke in a mouse model of aging

Upregulated long noncoding RNA Snhg1 promotes the angiogenesis of brain microvascular endothelial cells after oxygen-glucose deprivation treatment by targeting miR-199a.

Angiogenesis after ischemic stroke has important clinical significance, which stimulates endogenous recovery mechanisms and improves the neurological outcome. Enhancing angiogenesis may facilitate the function recovery from ischemic stroke. Recent studies have shown that aberrant expression of long noncoding RNAs (lncRNAs) is related to angiogenesis after ischemic stroke. Snhg1, a cancer-related lncRNA, has been reported to be upregulated after stroke. However, little is known about its role in stroke. In this study, we performed in vitro experiments to investigate the effects of Snhg1 on cell survival and angiogenesis and molecular mechanism in ischemic stroke. Oxygen-glucose deprivation/reoxygenation (OGD/R) was used to mimic ischemia/reperfusion injury in vitro. Sngh1 was increased in brain microvascular endothelial cells (BMECs) with the prolongation of exposure to OGD, and promoted BMEC survival under OGD/R condition, and angiogenesis after OGD/R treatment. miR-199a was identified and validated to be a direct target of Snhg1, and function effects of Snhg1 on BMEC survival and angiogenesis depended on miR-199a, which is involved in the regulation of hypoxia inducible factor and vascular endothelial cell growth factor expression. These findings contribute to a better understanding of the pathogenesis of ischemic stroke and facilitate the development of proangiogenesis therapy for this disease.

Lipopolysaccharide preconditioning increased the level of regulatory B cells in the spleen after acute ischaemia/reperfusion in mice

BackgroundThe inflammatory reaction of the spleen is an important component in the pathophysiology of cerebral ischaemia (CI). Regulatory B cells (Bregs) derived from the spleen can inhibit the expansion of inflammation and reduce the damage caused by CI. AimThe aim of the present study was to explore changes in spleen function and Bregs production due to lipopolysaccharide preconditioning (LPS PC) in ischaemia/reperfusion (I/R) and to uncover potential protective effect of LPS PC on stroke. MethodsFocal cerebral I/R mice were induced by middle cerebral artery occlusion (MCAO). Infarct size and inflammatory cell infiltration in brain tissue, athletic ability, and immune status were analysed by immunostaining, behavioural analyses, and flow cytometry, respectively. ResultsThe volume of the cerebral infarct was significantly decreased in I/R mice with LPS PC (LPS + I/R) compared to I/R mice, and neuronal apoptosis was ameliorated by LPS PC. After preconditioning with LPS, locomotor activity, forelimb strength, motor endurance, motor coordination, and short-term memory were improved to varying degrees. Moreover, blood-brain barrier (BBB) dysfunction was reversed, and CD11b+, major histocompatibility complex-II positive (MHC-II+), and Gr-1+ cell infiltration in the brains of LPS + I/R mice was also significantly reduced. B cell-activating factor (BAFF), tumour necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6 in the brain and spleen in the LPS + I/R group decreased to different degrees, while the levels of transforming growth factor-β (TGF-β) and IL-10 increased. LPS PC alleviated atrophy of the spleen following I/R. In addition, the number of CD8+ T cells, macrophages, TNF+ cells, NF-κB+ cells, and neutrophils in the spleen was reduced, while the number of proliferating cells and CD19+-IL10+ Bregs was significantly increased. The number of follicular B (FO B) cells and marginal zone B (MZ B) cells in the spleens of LPS + I/R mice was also increased. ConclusionsI/R mice preconditioned with LPS showed significantly reduced pathological damage, motor dysfunction, cognitive dysfunction, and inflammatory responses. LPS PC may initiate anti-inflammatory protective mechanism in the spleen after stroke, may increase the number of anti-inflammatory cells, such as Bregs, in the spleen, and may play a protective role in stroke.

Effect of Ginkgo biloba extract-761 on motor functions in permanent middle cerebral artery occlusion rats

BackgroundGinkgo biloba extract (EGb-761) has been in use to treat variety of ailments including memory loss and emotional disorders usually experienced after ischemic stroke. However, data regarding its protective role in stroke associated motor dysfunction is scarce. PurposeThe present work was designed to investigate the long-term effects of EGb-761 on the motor dysfunctions associated with permanent middle cerebral artery occlusion (pMCAO) in rats. Study Design/MethodsFocal ischemic stroke was induced in male Sprague–Dawley rats by pMCAO. These rats were orally administered with EGb-761 (25, 50, 100 mg/kg) and positive control butylphthalide (50 mg/kg) for up to 28 consecutive days. The motor function was evaluated by assessing neurological scores, rotarod performance and gait analysis after 7, 14, 21 and 28 days. After 28 days, the histological examination of in frontal cortex and hippocampus was also carried out. ResultsEGb-761 treatment significantly improved motor function with better outcome in coordination and gait impairment rats. EGb-761 (25, 50, 100 mg/kg) treatment for 28 days significantly decreased the neurological scores. After 28 days of treatment EGb-761 (50 and 100 mg/kg) significantly increased the latency in rotarod test, walk speed, and the body rotation, whereas, decreased the stride time and the left posterior swing length in gait were observed. EGb-761 (50, 100 mg/kg). EGb-761 (50, 100 mg/kg) significantly improved the pathological changes related to pMCAO. ConclusionsEGb 761 could improve motor function especially gait impairments among pMCAO rat model related to the decreased neuronal damage. Therefore, it might be the potential to be explored further as an effective therapeutic drug to treat post stroke motor dysfunctions.

Gamma‐glutamyl transferase predicts future stroke: A Korean nationwide study

Although gamma-glutamyl transferase (GGT) is generally regarded as an alternative biomarker for alcohol consumption, its independent role in vascular diseases emerged recently. However, its role in stroke remains unknown. The aim of this study is to clarify the impact of GGT on stroke in a large-sized, national, standardized population cohort in Korea. In Korea, the National Health Insurance Service (NHIS) provides full-coverage health insurance service for all citizens. Using data from the NHIS, the NHIS-National Sample Cohort was designed by randomly selecting 2% of Koreans, carefully considering demographic characteristics. We analyzed eligible individuals from this standardized cohort. The Cox proportional hazards model was used for the study investigating the relationship between GGT and stroke. Among the 456,100 eligible participants, 7,459 patients (1.64%) developed stroke as follows: 5,789 ischemic strokes, 1,046 intracerebral hemorrhages (ICHs), and 624 subarachnoid hemorrhages. GGT was independently correlated with increased risk of stroke after adjustment for alcohol consumption and stroke risk factors (hazard ratio [HR] = 1.39, 95% confidence interval [CI] = 1.29-1.51). The risks of both ischemic stroke (HR = 1.45, 95% CI = 1.32-1.58) and ICH (HR = 1.46, 95% CI = 1.18-1.80) were significantly elevated with increasing GGT. Despite some effect modifications by sex, age, and alcohol, the risk of total stroke and ischemic stroke in association with GGT remained significant in all subgroups. In a standard Korean population, GGT was a novel biomarker predicting stroke risk, independently from alcohol consumption and other risk factors. Ann Neurol 2018;83:375-386.

Abstract 142: Transgenic Overexpression of Krüppel-Like Factor 11 in Endothelium Ameliorates Ischemic Brain Injury

Introduction: Krüppel-like factors (KLFs) belong to zinc finger family of transcription factors and their roles in stroke are poorly explored. KLF11 is highly enriched in vascular endothelium, and we have previously documented that peroxisome proliferator-activated receptor gamma-mediated cerebral protection during ischemic insults needs KLF11 as a critical coactivator. However, the role of endothelial KLF11 itself in cerebrovascular function and stroke outcome is unclear. Hypothesis: We hypothesize that endothelium-targeted overexpression of KLF11 stabilizes the BBB, reduces the progression of brain damage, and improves neurological outcomes after ischemic stroke. Methods: Transient middle cerebral artery occlusion was performed in endothelial cell-selective KLF11 transgenic mice (EC-KLF11 Tg), and WT controls. BBB integrity was assessed by using Evans Blue and TMR-Dextran extravasation assays. Brain water content was measured by using a dry-wet method. Brain infarct was analyzed by 2%TTC staining. A battery of neurobehavioral tests, including rotarod, adhesive tape removal, and foot fault, were performed to assess sensorimotor functions. Total RNA was extracted from brain tissues and the expression of BBB tight junctions (TJs) was detected by qPCR and western blotting. Results: Compared to WT controls, EC-selective transgenic overexpression of KLF11 led to reduced BBB leakage in ischemic brains, evidenced by significantly reduced extravasation of BBB tracers and less brain water content. EC-KLF11 Tg mice also exhibited a smaller brain infarct and improved neurological functions in response to ischemic insults. Mechanistically, we found KLF11 binding sites in the promoter region of major endothelial TJs including Claudin 5 and ZO-1. EC-selective transgenic overexpression of KLF11 significantly increased cerebral TJ levels in mice after ischemic stroke. Conclusions: The present study has demonstrated that KLF11 functions at the EC level to preserve BBB structural and functional integrity and confers brain protection in ischemic stroke. KLF11 may be a novel therapeutic target for the treatment of ischemic stroke.

Abstract TP237: Improving Door to Needle (dtn) Times and Culture of Treating AIS Using a Stroke Alert RN (SA-RN)

Background and Purpose: In 2012 Saint Francis Hospital, a community hospital was challenged with extended DTN times, low treatment rates of AIS, and no formal inpatient stroke process. In 2012, primary stroke diagnosis volume was 614, only 13 patients were treated with Alteplase for AIS, with a DTN median of 92 minutes. Leaders were concerned with culture of not treating with Alteplase and desired improvement. Methods: Equip key clinical leaders for both Emergency and Inpatient stroke alerts, using a Neuro ICU nurse in the role of Stroke Alert Nurse (SA-RN) . 2012 SA-RN role was created to standardize assessments, NIHSS, administration of Alteplase, and monitoring post-procedure. Efforts were focused on improving time sensitive outcomes, i.e. DTN, LVO assessment, and BP control to mitigate s-ICH. The SA-RN role includes intensive training regarding care of the AIS patient. Audits were used to assure expected outcomes. Education included neuro anatomy and monthly case reviews allowing SA-RN Q&A. Results: Positive trends seen were (1) increased stroke alert volume, (2) decreased DTN, (3) increased Alteplase administrations. Stroke alert volume, both from the ER and the inpatient units, grew as the staff became more comfortable with stroke identification. Stroke Alerts: 2012 (179), 2013 (322), 2014 (405), 2015 (840), 2016 (1312) Alteplase Administrations: 2012 (13), 2013 (19), 2014 (17), 2015 (73), 2016 (156) DTN median: 2012 (92m), 2013 (76m), 2014 (62m), 2015 (56m), 2016 (44m) Conclusion: The addition of a clinical leader in the role of SA-RN is recommended for a stroke program with limited resources. The SA-RN allows for consistency of assessment, Alteplase administration, decreased DTN, increased compliance with post-Alteplase monitoring standards, and therefore decreased risk of s-ICH. The SA-RN is for Saint Francis Hospital as a valuable, trusted and consistent member of the stroke team.

Exosomes from Human Urine-Derived Stem Cells Promote Neurogenesis Via Histone Deacetylase6 Regulation in Ischemic Stroke

Background: Human urine-derived stem cells (USCs) are receiving much more attention in tissue regeneration and injury repair. Exosomes derived from USCs (USCs-Exo) have recently been suggested to mediate the restorative effects of USCs. However, whether USCs-Exo play a protective role in stroke remains unknown. Methods: Therapeutic effect of USCs-Exo in vivo was evaluated by cerebral infarction and neurological behavior. The proliferation and differentiation of neural stem cells (NSCs) was determined by double immunofluorescent staining. The viability, apoptosis, proliferation, and differentiation of NSCs subjected to oxygen glucose deprivation/reoxygenation (OGD/R) were assessed, respectively. The protein expression and activity of HDAC6, and the expression levels of miRNAs both in vivo and in vitro were assessed to detect the possible mechanism. Findings: We found that intravenous injection of USCs-Exo reduced brain infarct volume and improved functional recovery by enhancing the proliferation and differentiation of NSCs in ischemic rats. The in vitro results suggested that USCs-Exo increase viability, reduce apoptosis, and promote the proliferation and neuronal differentiation of NSCs after OGD/R. We further found that miR-206 contained in USCs-Exo is associated with the therapeutic efficacy for neurogenesis through the inhibition of histone deacetylase6 (HDAC6). Interpretation: Our study demonstrates that USCs-Exo can improve neurological function recovery by promoting neurogenesis, which is attributed to miR-206-mediated HDAC6 inhibition. Our research suggests that the use of USCs-Exo represents a novel therapeutic strategy for stroke recovery. Funding Statement: This work was funded by National Natural Science Foundation of China (Nos. 81671209, 81471243, and 81472152). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: Written informed consent was obtained from all of the volunteers, and all of the experimental procedures were approved by the Ethics Committee of the Shanghai Sixth People’s Hospital affiliated with Shanghai Jiaotong University.

Inhibition of NLRP3 Inflammasome Ameliorates Cerebral Ischemia-Reperfusion Injury in Diabetic Mice.

Sustained activation of NLRP3 inflammasome is closely related to diabetes and stroke. However, it is unknown whether NLRP3 inflammasome plays an essential role in stroke in diabetes. We aim to investigate the effect and the potential mechanism of NLRP3 inflammasome in diabetic mice with cerebral ischemia-reperfusion injury. A type 2 diabetic mouse model was induced by a high-fat diet and streptozotocin (STZ). Diabetic mice received MCC950 (the specific molecule NLRP3 inhibitor) or vehicle 60 minutes before the middle cerebral artery occlusion (MCAO) and reperfusion. MCC950 reduced the neurological deficit score of 24 h after cerebral ischemia reperfusion and improved the 28-day survival rate of cerebral ischemia-reperfusion injury in diabetic mice. Furthermore, we found that the mRNA transcription levels of NLRP3, IL-1β, and caspase-1 in the core ischemic area were remarkably amplified in diabetic mice with cerebral ischemia-reperfusion injury, whereas this phenomenon was obviously attenuated by MCC950 pretreatment. In conclusion, the NLRP3 inflammasome was involved in the complex diseases of diabetic stroke. MCC950, the NLRP3 specific inhibitor, ameliorated diabetic mice with cerebral ischemia-reperfusion injury and improved the 28-day survival rate during the recovery stage of ischemic stroke.

Potential application value of xenon in stroke treatment.

Stroke is an acute disease with extremely high mortality and disability, including ischemic stroke and hemorrhagic stroke. Currently only limited drugs and treatments have been shown to have neuroprotective effects in stroke. As a medical gas, xenon has been proven to have neuroprotective effect in considerable amount of previous study. Its unique properties are different from other neuroprotective agents, making it is promising to play a special therapeutic role in stroke, either alone or in combination with other treatments. In this article, we aim to review the role of xenon in the treatment of stroke, and summarize the mechanism of using xenon to produce therapeutic effects after stroke according to the existing research. Moreover, we intend to explore and demonstrate the feasibility and safety of xenon for clinical treatment of stroke. Despite the disadvantages of difficulty in obtaining and being expensive, as long as the use of reasonable methods, xenon can play an important role in the treatment of stroke.

Collateral response modulates the time-penumbra relationship in proximal arterial occlusions.

While clinical benefit from thrombolysis decreases with increase in time from stroke onset, the relationship of acute physiologic tissue compartments and collateral response to stroke onset time remains unclear. We studied consecutive patients with proximal arterial occlusions (n = 355) with whole-brain perfusion CT with CT angiography within 6 hours of stroke onset. Penumbra and core were defined using voxel-based thresholds. Tissue mismatch was defined as the ratio of penumbra to core. Collateral scores were assessed using a previously validated visual score. Mean (SD) age was 72.1 (12.4) years, median (interquartile range) NIH Stroke Scale score 16 (4), mean (SD) time to imaging 152.5 (69.7) minutes. Penumbra volume (Spearman ρ = 0.119, p = 0.026) and mismatch increased (Spearman ρ = 0.115, p = 0.030) with time from onset. Core volume decreased (Spearman ρ = -0.112, p = 0.035) while collateral scores increased with time (Spearman ρ = 0.117, p = 0.028). On multivariable regression, good collateral scores predicted longer time since onset (β = 0.101, p = 0.039) while mismatch was not a predictor (β = 0.001, p = 0.351). Good collateral score was the strongest independent predictor of final infarct volume and improvement in clinical deficit. In our large patient cohort study of proximal arterial occlusions, we found an incremental collateral response and preserved penumbral volume with time. Thus, tissue viability can be maintained in this time window (0-6 hours) after stroke if leptomeningeal collaterals are able to sustain the penumbra. Our findings suggest that a longer therapeutic window may exist for intra-arterial intervention and that multimodal imaging may have a role in strokes of unknown onset time.

Astrocyte Autophagy Flux Protects Neurons Against Oxygen-Glucose Deprivation and Ischemic/Reperfusion Injury.

The role of autophagy varies with the type of acute brain injury. In general, autophagy mediates a clear neuroprotective effect in intoxication caused by various psychoactive agents, subarachnoid hemorrhage and spinal cord injury. In contrast, autophagic cell death has also been reported to actively contribute to neuronal loss in neonatal hypoxic ischemic encephalopathy. However, it still remains to be determined whether autophagy pays a cytoprotective or a cytotoxic role in stroke. Previous studies focused primarily on the role of neurons rather than the role of astrocytes in brain injury. Thus, it is unknown whether modulating the autophagy flux of astrocytes contributes to improving neuronal survival after stroke. In the current study, we investigated the time course of autophagy flux in vitro using cocultured astrocytes and neurons exposed to oxygen-glucose deprivation/reoxygenation, which mimicked the process of ischemia/reperfusion. Autophagy flux of astrocytes was regulated by treatment with the autophagy inducer rapamycin, autophagy inhibitor 3-methyladenine, and the transduction of small interfering RNA against autophagy-related gene 5. In addition, AAV-GFAP-ATG7 was used to induce astrocyte autophagy flux in mice subjected to focal cerebral ischemia. We found that induction of autophagy flux of astrocytes in vitro enhanced the viability of neurons and decreased neuronal apoptosis. Furthermore, induction of astrocyte autophagy flux in mice improved neurological outcomes. In contrast, inhibition of autophagy flux in astrocytes decreased the viability of neurons and increased neuronal apoptosis. These results suggest that upregulation of autophagy flux in astrocytes may contribute to endogenous neuroprotective and neurorecovery mechanisms after stroke.

Galectin-3: an emerging biomarker in stroke and cerebrovascular diseases.

The carbohydrate-binding molecule galectin-3 has garnered significant attention recently as a biomarker for various conditions ranging from cardiac disease to obesity. Although there have been several recent studies investigating its role in stroke and other cerebrovascular diseases, awareness of this emerging biomarker in the wider neurology community is limited. We performed a systematic search in PubMed, Embase, Scopus, CINAHL, Clinicaltrials.gov and the Cochrane library in November and December 2016 for articles related to galectin-3 and cerebrovascular disease. We included both human and pre-clinical studies in order to provide a comprehensive view of the state of the literature on this topic. The majority of the relevant literature focuses on stroke, cerebral ischemia and atherosclerosis, but some recent attention has also been devoted to intracranial and subarachnoid hemorrhage. Higher blood levels of galectin-3 correlate with worse outcomes in atherosclerotic disease as well as in intracranial and subarachnoid hemorrhage in human studies. However, experimental evidence supporting the role of galectin-3 in these phenotypes is not as robust. It is likely that the role of galectin-3 in the inflammatory cascade within the central nervous system following injury is responsible for many of its effects, but its varied physiological functions and multiple sites of expression mean that it may have different effects depending on the nature of the disease condition and the time since injury. In summary, experimental and human research raises the possibility that galectin-3, which is closely linked to the inflammatory cascade, could be of value as a prognostic marker and therapeutic target in cerebrovascular disease.

Network pharmacology exploration reveals endothelial inflammation as a common mechanism for stroke and coronary artery disease treatment of Danhong injection

Although Danhong injection (DHI) is the most widely prescribed Chinese medicine for both stroke and coronary artery disease (CAD), its underlying common molecular mechanisms remain unclear. An integrated network pharmacology and experimental verification approach was used to decipher common pharmacological mechanisms of DHI on stroke and CAD treatment. A compound-target-disease & function-pathway network was constructed and analyzed, indicating that 37 ingredients derived from DH (Salvia miltiorrhiza Bge., Flos Carthami tinctorii and DHI) modulated 68 common targets shared by stroke and CAD. In-depth network analysis results of the top diseases, functions, pathways and upstream regulators implied that a common underlying mechanism linking DHI’s role in stroke and CAD treatment was inflammatory response in the process of atherosclerosis. Experimentally, DHI exerted comprehensive anti-inflammatory effects on LPS, ox-LDL or cholesterol crystal-induced NF-κB, c-jun and p38 activation, as well as IL-1β, TNF-α, and IL-10 secretion in vascular endothelial cells. Ten of 14 predicted ingredients were verified to have significant anti-inflammatory activities on LPS-induced endothelial inflammation. DHI exerts pharmacological efficacies on both stroke and CAD through multi-ingredient, multi-target, multi-function and multi-pathway mode. Anti-endothelial inflammation therapy serves as a common underlying mechanism. This study provides a new understanding of DHI in clinical application on cardiovascular and cerebrovascular diseases.

Circulatory Levels of C-X-C Motif Chemokine Ligands 1, 9, and 10 Are Elevated in Patients with Ischemic Stroke.

Inflammation plays a significant role in the development of ischemic stroke. CXC chemokines play pleiotropic roles in prolonged leukocyte locomotion, astrocyte migration/activation, and neural attachment/sprouting in response to focal stroke. In this study, we aimed to explore the changes in serum levels of three chemokines, C-X-C motif chemokine ligand 1 (CXCL1), C-X-C motif chemokine ligand 9 (CXCL9), and C-X-C motif chemokine ligand 10 (CXCL10), in ischemic stroke patients at the time of admission and before discharge from the hospital ward. In this study, we recruited 43 unrelated ischemic stroke patients using an easy convenience method or accidental sampling which is a type of non-probability sampling that involves the sample being drawn from that part of the population that is close to hand. We also enrolled 50 genetically unrelated healthy controls showing no history of neurologic, cardiovascular, or inflammatory diseases. Serum levels of the considered chemokines were measured by enzyme-linked immunosorbent assay (ELISA) in patients and healthy controls. No significant difference was observed in ischemic stroke patients following hospitalization and prior discharging from the hospital; however, there was a significant difference in serum levels of CXCL9 and CXCL10 between patients and healthy controls. We also found that the level of the chemokine was not related to gender or medical therapy. It appears that CXCL9 and CXCL10 are more predisposing factors and play a direct role in stroke considering that they were higher in patients than in healthy controls. We believe that this study might be used as a basis for further studies on more effective medication regimens to prevent the onset and subsequent complications of stroke. However, these mediators are useful diagnostic and prognostic tools rather than therapeutic tools.

Mural lymphatic endothelial cells regulate meningeal angiogenesis in the zebrafish.

Mural cells of the vertebrate brain maintain vascular integrity and function, play roles in stroke and are involved in maintenance of neural stem cells. However, the origins, diversity and roles of mural cells remain to be fully understood. Using transgenic zebrafish, we identified a population of isolated mural lymphatic endothelial cells surrounding meningeal blood vessels. These meningeal mural lymphatic endothelial cells (muLECs) express lymphatic endothelial cell markers and form by sprouting from blood vessels. In larvae, muLECs develop from a lymphatic endothelial loop in the midbrain into a dispersed, nonlumenized mural lineage. muLEC development requires normal signaling through the Vegfc-Vegfd-Ccbe1-Vegfr3 pathway. Mature muLECs produce vascular growth factors and accumulate low-density lipoproteins from the bloodstream. We find that muLECs are essential for normal meningeal vascularization. Together, these data identify an unexpected lymphatic lineage and developmental mechanism necessary for establishing normal meningeal blood vasculature.

Differentiating Stroke and Seizure in Acute Setting—Perfusion Computed Tomography?

Perfusion computed tomography (PCT) is part of acute stroke protocol in many hospitals; however, its clinical utility is still being disputed. Beyond its use in core and penumbra estimation, there is also a question about PCT role in stroke mimics diagnosis. Case series or small, retrospective studies showed equivocal results. This is the first published prospective, comparative study on PCT in differentiating stroke and seizure in acute setting. Patients with acute focal neurologic deficits and without acute ischemic lesions on routine CT underwent PCT and electroencephalography (EEG) within 12 hours after symptom onset. Perfusion parameters were set up as asymmetry indices for corresponding regions of brain hemispheres. EEG findings were assigned to 1 of 5 classes. Neurologic examination was performed using the National Institutes of Health Stroke Scale (NIHSS). Follow-up noncontrast computed tomography was performed on the third day after symptom onset. If no CT changes appeared, magnetic resonance diffusion-weighted imaging was conducted. Final diagnosis was hemispheric ischemic stroke in 17 patients and focal neurologic deficits in the course of seizures (post- and intraictally) in 12 patients. Those groups were significantly different only in one single PCT parameter-time to peak (TTP)-in the lateral part of the middle cerebral artery territory. Analyzed groups were not significantly different in the NIHSS scores and the EEG evaluation. TTP may stay relatively when seizure is a cause of focal neurologic deficits, but not stroke. Further, large, prospective studies are necessary to verify the results.

Endothelial glycocalyx as a critical signalling platform integrating the extracellular haemodynamic forces and chemical signalling.

The glycocalyx covers the human mammalian cells and plays important roles in stroke, inflammation and atherosclerosis. It has also been shown to be involved in endothelial mechanotransduction of shear stress. Shear stress induces the remodelling of the major component of the glycocalyx including glypican‐1, a cell membrane heparan sulphate proteoglycan. Other factors, such as sphingosine‐1‐phosphate (S1P), protect the glycocalyx against syndecan‐1 ectodomain shedding and induce the synthesis of heparan sulphate. In this study, we reviewed the role of shear stress and S1P in glycocalyx remodelling and revealed that the glycocalyx is a critical signalling platform, integrating the extracellular haemodynamic forces and chemical signalling, such as S1P, for determining the fate of endothelial cells and vascular diseases. This review integrated our current understanding of the structure and function of the glycocalyx and provided new insight into the role of the glycocalyx that might be helpful for investigating the underlying biological mechanisms in certain human diseases, such as atherosclerosis.

The role of nitric oxide in stroke.

Stroke is considered to be an acute cerebrovascular disease, including ischemic stroke and hemorrhagic stroke. The high incidence and poor prognosis of stroke suggest that it is a highly disabling and highly lethal disease which can pose a serious threat to human health. Nitric oxide (NO), a common gas in nature, which is often thought as a toxic gas, because of its intimate relationship with the pathological processes of many diseases, especially in the regulation of blood flow and cell inflammation. However, recent years have witnessed an increased interest that NO plays a significant and positive role in stroke as an essential gas signal molecule. In view of the fact that the neuroprotective effect of NO is closely related to its concentration, cell type and time, only in the appropriate circumstances can NO play a protective effect. The purpose of this review is to summarize the roles of NO in ischemic stroke and hemorrhagic stroke.

Cell Death Mechanisms of Neurodegeneration.

There are common mechanisms shared by genetically or pathologically distinct neurodegenerative diseases, such as excitotoxicity, mitochondrial deficits and oxidative stress, protein misfolding and translational dysfunction, autophagy and microglia activation. This indicates that although the original cause may differ in individual diseases or even subtypes of certain disorders, these disrupted common cell functions and signaling, together with aging, may lead to final execution of cell death through similar pathways. The variable neurodegenerative disease symptoms are probably caused by the type, location, and connection of the cell populations that suffer from dysfunction and loss. Besides apoptosis, necroptosis, and autophagy, an important form of death termed parthanatos plays a prominent role in stroke and several neurodegenerative diseases, which is due to PARP-1 overactivation, PAR accumulation, nuclear translocation of the mitochondria protein AIF, and large-scale DNA cleavage. Understanding the mechanisms and interactions of cell death signaling will not only help to develop neuroprotective strategies to halt neurodegeneration, but also provide biomarkers for monitoring disease progression and recovery.