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Background: The optimum systolic blood pressure after endovascular thrombectomy for acute ischaemic stroke is uncertain. We aimed to compare the safety and efficacy of blood pressure lowering treatment according to more intensive versus less intensive treatment targets in patients with elevated blood pressure after reperfusion with endovascular treatment. Methods: We conducted an open-label, blinded-endpoint, randomised controlled trial at 44 tertiary-level hospitals in China. Eligible patients (aged ≥18 years) had persistently elevated systolic blood pressure (≥140 mm Hg for >10 min) following successful reperfusion with endovascular thrombectomy for acute ischaemic stroke from any intracranial large-vessel occlusion. Patients were randomly assigned (1:1, by a central, web-based program with a minimisation algorithm) to more intensive treatment (systolic blood pressure target

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by CAG repeat mutations in the ATXN1 gene. In this study, we generated an induced pluripotent stem cell line (iPSC) by using non-integrating Sendai virus (SeV) from peripheral blood mononuclear cells(PBMCs)of SCA1 patient harboring a CAG repeat mutation in the ATXN1 gene. The induced patient-specific iPSC line with a normal karyotype and expresses pluripotent markers, it also shows differentiation totipotency and tridermogenesis in vitro. It may be an excellent model for studying spinocerebellar ataxia type 1 (SCA1) in vitro and will be beneficial for studying SCA1 pathogenesis and therapeutic intervention strategies.

It is important to determine the functional changes of organs that occur as a result of aging, the understanding of which may lead to the maintenance of a healthy life. Glucose metabolism in healthy bodies is one of the potential markers used to evaluate the changes of organ function. Thus, information about normal organ glucose metabolism may help to understand the functional changes of organs. [18F]-Fluoro-2-deoxy-2-d-glucose (18F-FDG), a glucose analog, has been used to measure glucose metabolism in various fields, such as basic medical research and drug discovery. However, glucose metabolism changes in aged animals have not yet been fully clarified. The aim of this study is to evaluate changes in glucose metabolism in organs and brain regions by measuring 18F-FDG accumulation and 18F-FDG autoradiography with insulin loading in aged and young wild-type mice. In the untreated groups, the levels of 18F-FDG accumulation in the blood, plasma, muscle, lungs, spleen, pancreas, testes, stomach, small intestine, kidneys, liver, brain, and brain regions, namely, the cortex, striatum, thalamus, and hippocampus, were all significantly higher in the aged mice. The treated group showed lower 18F-FDG accumulation levels in the pancreas and kidneys, as well as in the cortex, striatum, thalamus, and hippocampus in the aged mice than the untreated groups, whereas higher 18F-FDG accumulation levels were observed in those in the young mice. These results demonstrate that insulin loading decreases effect on 18F-FDG accumulation levels in some organs of the aged mice. Therefore, aging can increase insulin resistance and lead to systemic glucose metabolism dysfunction.

Long noncoding RNA nuclear enriched abundant transcript 1 (NEAT1) has been reported to be involved in depression. This study aims to investigate the mechanism of NEAT1/microRNA (miR)-320-3p/Corticotropin-releasing hormone receptor 1 (CRHR1) axis in depressed rats. Rats with depression-like behaviors were prepared by exposing the rats to chronic unpredictable mild stress. Behavioral functions, pathological damage, neuronal apoptosis and monoamine neurotransmitter were examined in depressed rats . Primary hippocampal neurons were injured through simulation with corticosterone(CORT). Cell viability and apoptosis were measured in CORT-Induced hippocampal neurons. The binding relationship between NEAT1 and miR-320-3p and the targeting relationship between miR-320-3p and CRHR1 were detected. Elevated NEAT1, CRHR1 and reduced miR-320-3p exhibited in depressed rats and CORT-treated hippocampal neurons, NEAT1 bound to miR-320-3p to target CRHR1. Silencing NEAT1 or elevating miR-320-3p improved behavioral functions, attenuated pathological damage and apoptosis in the hippocampus, and increased monoamine neurotransmitter in depressed rats. Repression of NEAT1 or promotion of miR-320-3p enhanced viability and suppressed apoptosis of CORT-treated hippocampal neurons. The study highlights that NEAT1 competitively binds to miR-320-3p to up-regulate CRHR1 expression, thereby promoting hippocampal damage of depressed rats.

Myocardial fibrosis detected by cardiac magnetic resonance (CMR) has been reported in patients with desmin‐related myopathy, although its characteristics remain unclear. Here, we describe a case of desmin‐related restrictive cardiomyopathy wherein CMR imaging revealed myocardial oedema, ischaemia, and fibrosis in the left ventricle; the different types and processes of myocardial injury were detected by CMR. Middle wall left ventricular enhancement may be a feature of late gadolinium enhancement, and the lateral wall is often involved in cases of myocardial injury. CMR is useful for the early detection of cardiac involvement and the prediction of prognosis in patients diagnosed with desmin‐related myopathy.

BackgroundMechanical thrombectomy is the standard treatment for acute ischemic stroke (AIS) with large vessel occlusion (LVO) in the anterior circulation. This trial aimed to indicate whether Skyflow, a new thrombectomy device, could achieve the same safety and efficacy as Solitaire FR in the treatment of AIS.MethodsThis study was a prospective, multicenter, randomized, single blind, parallel, positive controlled, non-inferiority clinical trial. Patients with intracranial anterior circulation LVO within 8 hours from onset were included to receive thrombectomy treatment with either the Skyflow or Solitaire FR stent retriever. The primary endpoint was the rate of successful reperfusion (modified Treatment In Cerebral Infarction (mTICI) ≥2b) after the operation. The safety endpoints were the rate of symptomatic intracranial hemorrhage (sICH) and subarachnoid hemorrhage (SAH) at 24 hours after operation.ResultsA total of 95 and 97 patients were involved in the Skyflow group and Solitaire FR group, respectively. A successful reperfusion (mTICI ≥2b) was finally achieved in 84 (88.4%) patients in the Skyflow group and 80 (82.5%) patients in the Solitaire FR group. Skyflow was non-inferior to Solitaire FR in regard to the primary outcome, with the criterion of a non-inferiority margin of 12.5% (p=0.0002) after being adjusted for the combined center effect and the National Institutes of Health Stroke Scale (NIHSS) score. The rate of periprocedural sICH and SAH did not differ significantly between the two groups.ConclusionEndovascular thrombectomy with the Skyflow stent retriever was non-inferior to Solitaire FR with regard to successful reperfusion in AIS due to LVO (with a pre-specified non-inferiority margin of 12.5%).

Purpose: The Tonbridge stent is a novel retriever with several design improvements which aim to achieve promising flow reperfusion in the treatment of acute ischemic stroke (AIS). We conducted a randomized controlled, multicenter, non-inferiority trial to compare the safety and efficacy of the Tonbridge stent with the Solitaire FR.Methods: AIS patients aged 18–85 years with large vessel occlusion in anterior circulation who could undergo puncture within 6 h of symptom onset were included. Randomization was performed on a 1:1 ratio to thrombectomy with either the Tonbridge stent or the Solitaire FR. The primary efficacy endpoint was successful reperfusion using a modified thrombolysis in cerebral infarction score (mTICI) of 2b/3. Safety outcomes were symptomatic intracranial hemorrhage (sICH) within 24 ± 6 h and all-cause mortality within 90 days. A clinically relevant non-inferiority margin of 12% was chosen as the acceptable difference between groups. Secondary endpoints included time from groin puncture to reperfusion, National Institutes of Health Stroke Scale (NIHSS) score at 24 h and at 7 days, and a modified Rankin Scale (mRS) score of 0–2 at 90 days.Results: A total of 220 patients were enrolled; 104 patients underwent thrombectomy with the Tonbridge stent and 104 were treated with the Solitaire FR. In all test group patients, the Tonbridge was used as a single retriever without rescuing by other thrombectomy devices. Angioplasty with balloon and/or stent was performed in 26 patients in the Tonbridge group and 16 patients in the Solitaire group (p = 0.084). Before angioplasty, 86.5% of those in the Tonbridge group and 81.7% of those in the Solitaire group reached successful reperfusion (p = 0.343). Finally, more patients in the Tonbridge group achieved successful reperfusion (92.3 vs. 84.6%, 95% CI of difference value 0.9–16.7%, p < 0.0001). There were no significant differences on sICH within 24 ± 6 h between the two groups. All-cause mortality within 90 days was 13.5% in the Tonbridge group and 16.3% in the Solitaire group (p = 0.559). We noted no significant differences between groups on the NIHSS at either 24 h or 7 days and the mRS of 0–2 at 90 days.Conclusion: The trial indicated that the Tonbridge stent was non-inferior to the Solitaire FR within 6 h of symptom onset in cases of large vessel occlusion stroke.Clinical Trial Registration:ClinicalTrials.gov, number: NCT03210623.

Two recently published JNIS commentaries1 2 on eligibility criteria for the clinical trials on patients with large core, acute ischemic stroke (AIS) with large vessel occlusion have caused some debate. Five trials were included.1 Our ongoing trial, ANGEL-ASPECT (NCT 04551664), which represents the only large core trial currently ongoing in the Chinese population, was not included in the discussion. One issue of the debate is the addition of CT perfusion (CTP)/diffusion-weighted image of magnetic resonance imaging (DWI-MRI) to the inclusion criteria, which only the SELECT-2 trial chose to adopt. This raised concern about whether patients already known to benefit from endovascular thrombectomy (EVT) are being randomized to EVT treatment or no treatment. Like the SELECT-2 trial, our ANGEL-ASPECT trial also added CTP/DWI-MRI to our inclusion criteria, but in a manner different from SELECT-2. Here we review the merits of ANGEL-ASPECT’s design and suggest that it be included in the discussion of patient selection criteria in large core trials. The ANGEL-ASPECT trial is an ongoing, multicenter, randomized controlled trial (RCT) currently being conducted in China and sponsored by Beijing Tiantan Hospital. Patients are enrolled according to a prespecified protocol. Each randomized patient is qualified by two core laboratory members who are available at all hours to calculate Alberta Stroke Program Early CT Score (ASPECTS) and infarct core volume using the specialized RAPID software. As for the other five trials discussed in the commentary by Jadhav et al ,1 the primary goal of our trial is to determine whether EVT will benefit or harm patients with AIS and large vessel occlusion and a ‘large core’ infarct. While the ANGEL-ASPECT and SELECT-2 trials both include core volume as defined by CTP in the inclusion criteria in addition to ASPECTS, the other four trials define large core using only ASPECTS. The …

Cerebral ischemia/reperfusion (I/R) injury is associated with various cardiovascular and cerebrovascular diseases with high disability, morbidity, and mortality rates. MicroRNAs (miRNAs) are related to the pathogenesis of the above diseases. MiR-505-5p, a kind of such miRNAs, was found to be highly expressed in cerebral I/R injuries, but the mechanism of action of this miRNA in cerebral I/R injury was unclear. In our study, up-regulation of miR-505-5p was detected in cultured oxygen-glucose deprivation/reoxygenation (OGD/R)-subjected PC12 and HEC293 cells. Silencing of miR-505-5p in OGD/R-affected neuron-like cells not only decreased the OGD/R-injury (according to cell viability, SOD increase, and LDH and MDA decreases), but also reduced apoptosis (decreasing the cleaved caspase-3 and PARP protein levels). Interestingly, expression of CREG1 (Cellular Repressor of E1Astimulated Genes 1) was low in OGD/R-subjected neurons; it was verified as a possible target gene of miR-505-5p. CREG1 knockdown can reverse the effect of miR-505-5p silencing in OGD/R-induced neural injury. Taken together, the data obtained provide a new target for cerebral I/R injury treatment.

Background Primary angiitis of the central nervous system (PACNS) is a rare disease, and tumor-like primary angiitis of the central nervous system is even rarer. Histopathology is the gold standard for tumor-mimicking PACNS. However, pathological diagnosis is relatively limited due to fewer biopsy opportunities. Case presentation A 68-year-old male presented with ataxia, and was diagnosed with tumor-like primary angiitis of the central nervous system. The patient underwent Intravenous drip glucocorticoid therapy (10 mg of dexamethasone, daily). After 10 days, the symptoms of the patient were completely relieved. Radiology revealed that the low density lesion in the right cerebellar hemisphere obviously narrowed. Cyclophosphamide therapy was not initiated. Conclusion It is crucial for clinicians to be aware of changes in radiology that indicate PACNS, since the diagnosis of tumor-like PACNS remains quite challenging. Glucocorticoid therapy is an effective therapy in this condition, and the prognosis can be favorable.

Recently, a wealth of information has emerged connecting the activation of the NLRP3 (NOD-like receptor family pyrin domain-containing 3) inflammasome to stroke pathogenesis, although the exact influence of the NLRP3 inflammasome on stroke is still in the stage of preliminary study and is awaiting further confirmation. In this paper, we will review the structure, assembly and activation of the NLRP3 inflammasome and its expression in the neurovascular units and will speculate on its possible roles in neurovascular injury post-stroke. Evidence on this topic suggests that targeting NLRP3-mediated inflammation at multiple levels may provide a new therapeutic strategy to prevent the deterioration of neurovascular units after stroke. However, many aspects of the biological link between the NLRP3 inflammasome and stroke remain ill-defined or even completely unknown. As fresh insights come to light regarding the NLRP3 inflammasome, the opportunities to develop new therapeutic strategies for stroke patients are expected to improve accordingly.

Introduction: Guillain–Barre syndrome (GBS) is an acute immune-mediated inflammatory demyelinating polyneuropathy characterized by symmetrical limb weakness and areflexia. GBS can have different clinical manifestations; hence, the initial symptoms are also varied. Here, we describe a rare case of GBS presenting as hemiparesis and cranial nerve palsy, which mimic brainstem stroke.Case Presentation: A 53-year-old man was admitted to the hospital with a 3-h history of left-arm weakness, glossolalia, and right eyelid droop. After admission, his condition suddenly worsened, with quadriplegia, bilateral peripheral facial palsy, bilateral ophthalmoplegia, and other neurological symptoms. Based on the findings from a neurological examination, MRI, cerebrospinal fluid analysis, and nerve conduction study, a diagnosis of GBS was made. He received intravenous immunoglobulin (0.4 kg/day) for 5 days. After 20 days of systematic therapy, his dysphagia, dyspnea, facial paralysis, ocular movement disorder, and leg weakness recovered almost completely, but his arms were still moderately impaired, with a power of 4/5. Fortunately, the patient recovered well without any sequelae after 2 years of follow-up.Conclusions: In patients with an atypical presentation, the diagnosis of GBS is often delayed. With this case report, we intend to highlight the fact that some symptoms mimicking stroke may be a feature of GBS at onset; close observation and timely diagnosis are crucial for clinicians. Neuroimaging is a valuable diagnostic tool in differentiating stroke from GBS.

It is important to determine the functional changes of organs that occur as a result of aging, the understanding of which may lead to the maintenance of a healthy life. Glucose metabolism in healthy bodies is one of the potential markers used to evaluate the changes of organ function. Thus, information about normal organ glucose metabolism may help to understand the functional changes of organs. [18F]-Fluoro-2-deoxy-2-D-glucose (18F-FDG), a glucose analog, has been used to measure glucose metabolism in various fields, such as basic medical research and drug discovery. However, glucose metabolism changes in super-aged animals have not yet been fully clarified. The aim of this study is to evaluate changes in glucose metabolism in organs and brain regions by measuring 18F-FDG accumulation and 18F-FDG autoradiography with insulin loading in super-aged and young wild-type mice. In control groups, the levels of 18F-FDG accumulation in the blood, plasma, muscle, lungs, spleen, pancreas, testes, stomach, small intestine, kidneys, liver, brain, and brain regions, namely, the cortex, striatum, thalamus, and hippocampus, were all significantly higher in the super-aged mice. After insulin loading, the 18F-FDG accumulation levels showed negative changes in the pancreas and kidneys, as well as in the cortex, striatum, thalamus, and hippocampus in the super-aged mice, whereas positive changes were observed in those in the young mice. These results demonstrate that insulin loading decreases effect on 18F-FDG accumulation levels in some organs of the super-aged mice. Therefore, aging can increase insulin resistance and lead to systemic glucose metabolism dysfunction.

It is important to determine the functional changes of organs that occur as a result of aging, the understanding of which may lead to the maintenance of a healthy life. Glucose metabolism in healthy bodies is one of the potential markers used to evaluate the changes of organ function. Thus, information about normal organ glucose metabolism may help to understand the functional changes of organs. [18F]-Fluoro-2-deoxy-2-d-glucose (18F-FDG), a glucose analog, has been used to measure glucose metabolism in various fields, such as basic medical research and drug discovery. However, glucose metabolism changes in aged animals have not yet been fully clarified. The aim of this study is to evaluate changes in glucose metabolism in organs and brain regions by measuring 18F-FDG accumulation and 18F-FDG autoradiography with insulin loading in aged and young wild-type mice. In the untreated groups, the levels of 18F-FDG accumulation in the blood, plasma, muscle, lungs, spleen, pancreas, testes, stomach, small intestine, kidneys, liver, brain, and brain regions, namely, the cortex, striatum, thalamus, and hippocampus, were all significantly higher in the aged mice. The treated group showed lower 18F-FDG accumulation levels in the pancreas and kidneys, as well as in the cortex, striatum, thalamus, and hippocampus in the aged mice than the untreated groups, whereas higher 18F-FDG accumulation levels were observed in those in the young mice. These results demonstrate that insulin loading decreases effect on 18F-FDG accumulation levels in some organs of the aged mice. Therefore, aging can increase insulin resistance and lead to systemic glucose metabolism dysfunction.

Bilateral medial medullary infarction is a rare stroke subtype, and its diagnosis has become possible by brain magnetic resonance imaging. In this report, we describe a case in which acute bilateral medial medullary infarction accompanied by cerebral watershed infarction was clearly identified by diffusion-weighted imaging, and we discuss the mechanisms of bilateral medial medullary infarction accompanied by cerebral watershed infarction.

BACKGROUND The current study was designed to explore the pathway through which adipose-derived mesenchymal stem cells (ADMSCs) affect brain ischemic injury. MATERIAL AND METHODS The improving effect of ADMSCs on the brain function and structure was evaluated in a middle cerebral artery occlusion (MCAO) rat model. The permeability of the brain-blood barrier (BBB), inflammatory response, and endoplasmic reticulum (ER) stress-related signaling induced by ischemia were determined. RESULTS The administration of ADMSCs decreased neurological severity score when compared with that in the MCAO group and also restricted the brain infarction area as well as cell apoptosis. ADMSCs suppressed the inflammation in brains by decreasing the expressions of IL-1β, IL-6, and TNF-α, contributing to the decreased permeability of the BBB. The expressions of pro-apoptosis factors in ER stress were inhibited while that of anti-apoptosis factors were induced. CONCLUSIONS ADMSCs affected brain injury in multiple ways, not only by suppressing inflammation in the brain infarction area, but also by blocking ER stress-induced apoptosis.

Background Complications of the internal carotid artery (ICA) in surgery are rare but severe. This study aimed to locate the ICA with 5 stationary bony structures in the sellar region: the anterior clinoid process, the tuberculum sellae, the bottom of the hypophyseal fossa, the posterior edge of the hypophyseal fossa, and the postclinoid process and to do measurements to determine their anatomic relationship with the ICA. Methods After multiple planar reconstructions on computer tomographic angiography images of 120 ICA in 60 individuals, we defined the 5 bony structures as 5 origins in the horizontal, sagittal, and vertical planes with the 3D coordinate system and got the cross-sections of bilateral ICA on the coronal plane passing through each origin. We measured the distances between the cross-sections and the origins and angles between the horizontal plane and the line passing through the origin and the cross-sections on each coronal plane. We also measured the distances between the bilateral ICA on the 5 coronal planes. Besides, we measured the coordinate of the anterior edge of bilateral ICA, taking the anterior clinoid process as the origin. Results With the 3-dimensional coordinate system, we located the ICA to the bony structures in skull base. The distance between the bilateral ICA on coronal planes were 18.8 ± 2.9 mm, 23.6 ± 3.7 mm, 19.9 ± 3.4 mm, 24.7 ± 4.3 mm, and 23.5 ± 3.5 mm, from anterior to posterior, respectively. Conclusion The 3D coordinate system used in this study is of value in preoperational assessment, and data we obtained indicate the safety ranges avoiding damage to the ICA in surgery.

Signaling pathways are critical modulators of a variety of physiological and pathological processes, and the abnormal activation of some signaling pathways can contribute to disease progression in various conditions. As a result, signaling pathways have emerged as an important tool through which the occurrence and development of diseases can be studied, which may then lead to the development of novel drugs. Accumulating evidence supports a key role for extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in the embryonic development of the central nervous system (CNS) and in the regulation of adult brain function. ERK1/2, one of the most well characterized members of the mitogen-activated protein kinase family, regulates a range of processes, from metabolism, motility and inflammation, to cell death and survival. In the nervous system, ERK1/2 regulates synaptic plasticity, brain development and repair as well as memory formation. ERK1/2 is also a potent effector of neuronal death and neuroinflammation in many CNS diseases. This review summarizes recent findings in neurobiological ERK1/2 research, with a special emphasis on findings that clarify our understanding of the processes that regulate the plethora of isoform-specific ERK functions under physiological and pathological conditions. Finally, we suggest some potential therapeutic strategies associated with agents acting on the ERK1/2 signaling to prevent or treat neurological diseases.

Neuropsychiatric symptoms have been well documented after subthalamic nucleus deep brain stimulation (STN-DBS), but those following a subthalamic lesion have been rarely reported. Herein, we present a 43-year-old woman with sudden-onset dramatic psychiatric and behavioral symptoms with hemiballism. Brain magnetic resonance imaging (MRI) with fluid attenuated inversion recovery (FLAIR) sequence during the acute phase demonstrated extensive hyperintensity in the left STN and adjacent regions. Contrast-enhanced MRI showed no abnormal areas of enhancement. Magnetic resonance venography (MRV) was normal. Routine blood and cerebrospinal fluid (CSF) tests were not remarkable. Autoimmune antibodies showed no significant results. A gradual recovery of both psychiatric and behavioral symptoms and hemiballism was observed with steroid and symptomatic treatment. Our case is unique in dramatic neuropsychiatric symptoms following a subthalamic lesion. We would like to point out that severe neuropsychiatric symptoms can occur in the patients with subthalamic lesions, and can be a troubling feature in their management.

The continually increasing number of patients with type 2 diabetes is a worldwide health problem, and the incidence of microvascular complications is closely related to type 2 diabetes. Structural brain abnormalities are considered an important pathway through which type 2 diabetes causes brain diseases. In fact, there is considerable evidence that type 2 diabetes is associated with an increased risk of structural brain abnormalities such as lacunar infarcts (LIs), white matter hyperintensities (WMHs), and brain atrophy. WMHs are a common cerebral small-vessel disease in elderly adults, and it is characterized histologically by demyelination, loss of oligodendrocytes, and vacuolization as a result of small-vessel ischemia in the white matter. An increasing number of studies have found that diabetes is closely related to WMHs. However, the exact mechanism by which type 2 diabetes causes WMHs is not fully understood. This article reviews the mechanisms of type 2 diabetes-related WMHs to better understand the disease and provide help for better clinical treatment.

Gastric cancer (GC) remains to be a familiar malignant tumor with poor prognosis and daunting impacts on global health. We planned to grab the latent impacts of microRNA-183 in regulating cell autophagy, thus to clarify its possible regulatory principle in GC. The miR-183 level in GC tissues and cell lines was investigated. The impacts of miR-183 dysregulation on cell biological performances including viability, apoptosis and autophagy of GC cell lines including SGC-7901 were detected. Also, cells were disposed with 3-methyladenine (3-MA, an autophagy inhibition) before dysregulation of miR-183 to further investigate the correlation between cell autophagy and viability or apoptosis. Furthermore, the regulatory mechanisms between miR-183 and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), silent mating type information regulation 1 (SIRT1) or PI3K/AKT/mTOR pathway were explored. miR-183 was under-expressed both in GC tissues and in cell lines. miR-183 mimic alone depressed SGC-7901 cell viability and enhanced cell apoptosis and autophagy, whereas miR-183 inhibitor exhibited opposite effects. Moreover, the impacts of miR-183 on SGC-7901 cell viability and apoptosis were mediated by affecting the activation of autophagy. Our results indicate that miR-183 is under-expressed in GC cells and depression of miR-183 may enhance GC cell viability and inhibit cell apoptosis by affecting the activation of cell autophagy. MALAT1-miR-183-SIRT1 axis and PI3K/AKT/mTOR pathway may be mechanisms to mediate autophagy in GC. miR-183 may serve as a towardly therapeutic target for GC.

Ischemic stroke (IS) is a cerebrovascular disease with serious neurological function impairment, which may activate endoplasmic reticulum (ER) stress. However, the underlying regulatory mechanism of ER stress under IS remains unclear. miR-9-5p is enriched in the brain tissues and plays a role in the pathological process of IS. Therefore, the purpose of this study is to explore the effect of miR-9 on ER stress and underlying mechanism in IS. Here, a middle cerebral artery occlusion (MCAO) rat model was utilized to examine the alteration of brain pathology, and the expressions of miR-9 and ER stress-related proteins. Then SH-SY5Y cells with oxygen-glucose deprivation (OGD) were performed to further evaluate the functional role of miR-9 and preliminary mechanism. The results showed that miR-9 levels were decreased in the ischemic region of rats after MCAO. MCAO significantly increased the brain infract volume, reduced Nissl bodies and cell apoptosis, and increased ER stress-related proteins (ERMP1, GRP78, p-PERK, p-eIF2α and CHOP). Furthermore, overexpression of miR-9 by miR-9 mimics increased cell viability, inhibited LDH activity and cell apoptosis, and inactivated ER stress in OGD-neurons. Luciferase activity results showed that miR-9 negatively regulated ERMP1 expression by directly targeting ERMP1 3' UTR. Subsequently, we found that ERMP1 overexpression reversed the inhibition of miR-9 on GRP78-PERK-CHOP pathway in OGD neurons. In summary, our results suggest that the attenuation of miR-9 on ischemic injury may be involved in targeting ERMP1-mediated ER stress, which provides an available target for IS treatment.

Objective: Atherosclerosis is closely associated with ischemic stroke, and long noncoding RNA-H19 (lncRNA-H19) might be a potential target for treating atherosclerosis. The present study aimed to investigate the function of lncRNA-H19 in atherosclerosis and to explore a novel therapeutic strategy for ischemic stroke. Methods: Differentially expressed genes (DEGs) in atherosclerosis were screened by searching public database. In combination with the lncRNA-H19-knockout database, potential lncRNA-H19-mediated gene was retrieved and their relationship was identified. In order to assess the detailed regulatory mechanism of lncRNA-H19, we used a lentivirus packaging system to upregulate Acp5 (Acid phosphatase 5) expression in vascular smooth muscle cells (VSMC) and human umbilical vein endothelial cells (HUVECs). The expression of ACP5 was determined by Western Blot, and evaluations of cell proliferation and apoptosis were detected. An ischemic stroke mouse model was established. Atherosclerosis was measured by using plaque area size. The effects H19 on the expression of ACP5 were explored by the overexpression or silence of H19. Results: H19 and ACP5 were associated with Acute Stroke Treatment (TOAST) subtypes of atherosclerotic patients. The target prediction program and dual-luciferase reporter confirmed ACP5 as a direct target of H19. Lentivirus-mediated H19-forced expression upregulated ACP5 protein levels, promoted cell proliferation and suppressed the apoptosis. The plaque area size was larger in ischemic models than controls. The overexpression or silence of H19 increased or reduced the plaque size. The overexpression or silence of H19 resulted in the expression or inhibition of ACP5. Conclusion: IncRNA-H19 promoting ACP5 protein expression contributed to atherosclerosis and increased the risk of ischemic stroke.

Angiogenesis refers to new capillaries that sprout and remold from existing vessels. The mechanism of angiogenesis is very complex. Many factors promote angiogenesis in the body, and many factors inhibit angiogenesis. Angiogenesis is closely correlated to oxidative stress. Oxidative stress plays an important role in its positive feedback mechanism. Oxidative stress is defined as the imbalance of the internal oxidation system and antioxidant system, which is correlated to the cause and prognosis of many vascular diseases, and can be used as a biomarker for these diseases. At the same time, good regulation of oxidative stress can promote angiogenesis and tissue repair. Therefore, the present study summarizes the relationship between oxidative stress and angiogenesis, and new progress, and discusses the effect and mechanism of oxidative stress on angiogenesis.

Rationale: Neuromyelitis optica spectrum disorders (NMOSDs) represent recurrent autoimmune diseases, generally beginning with optic nerve neuritis or acute transverse myelitis. Patient concerns: A 57-year-old male with long-term alcohol intake was hospitalized because of limb numbness. EMG examination showed the peripheral sensory nerve was in demyelination and an axonal injury was found. His symptoms could not be improved by vitamin B injection but were later significantly attenuated by dexamethasone treatment. Four months later, symptoms of optic neuritis in the left eye appeared, and 6 months later he exhibited peripheral neuropathy with acute myelitis. Diagnoses: He was diagnosed NMOSD. Outcomes: Immunotherapy improved his peripheral neuropathy and myelitis symptoms. Lessons: NMOSD patients could represent peripheral neuropathy as the first episode.

Ischemic stroke is a major cerebrovascular disease resulting from a transient or permanent local reduction of cerebral blood flow. Angiogenesis plays an important role in cerebral microvascular repair after ischemic stroke. This study aimed at investigating the effect of NF-E2-related factor 2 (Nrf2) on the angiogenesis of mouse cerebral microvascular endothelial bEnd.3 cells in a hypoxic environment. We found that Nrf2 expression was temporarily increased in hypoxia-induced bEnd.3 cells. Knockdown of Nrf2 inhibited the proliferation, migration, as well as tube formation in hypoxia-induced bEnd.3 cells. Meanwhile, vascular endothelial growth factor and PI3K/Akt signaling pathways were identified to be regulated by Nrf2 in hypoxia-induced bEnd.3 cells. It was found that silencing of Nrf2 downregulated the expression levels of NAD(P)H:quinine oxidoreductase-1, vascular endothelial growth factor, p-Akt, and heme oxygenase-1 in hypoxia-induced bEnd.3 cells. Data suggested that hypoxia induced the transient increase of Nrf2, which plays a key role in the angiogenesis of cerebral microangiogenesis, and that Nrf2 regulates the proliferation, migration, as well as tube formation likely through PI3K/Akt signaling pathway in hypoxia-induced bEnd.3 cells. Our study provides proof of concept for the modulation of Nrf2, so as to tilt the balance toward angiogenesis, representing a therapeutic strategy for hypoxia or ischemia disorders such as stroke.

Rationale: Intracranial arterial dissection is a rare cause of ischemic stroke, and isolated middle cerebral artery dissection (MCAD) is extremely rare, having been described only in sparse case reports. The etiology, clinicoradiological features, and treatment strategies are not yet well understood. Patient concerns: A 49-year-old man presented with rapidly progressive aphasia and motor disturbance of the right limbs. Diagnoses: Neuroimaging evaluation confirmed a diagnosis of MCAD and cerebral infarction. Interventions: The patient underwent oral anti-platelet therapy (100 mg aspirin daily). Outcomes: The patient recovered to normal status within 2 weeks following antiplatelet treatment. During a follow-up period of 2 years, he remained neurologically asymptomatic and led a virtually normal life. Lessons: It is crucial for clinicians to be aware of this entity, as the diagnosis of MCAD is quite challenging. Antiplatelet therapy is effective for treating this condition, and the prognosis can be favorable.

Stroke is the loss of brain function due to a disturbance in the blood supply to the brain resulting from either ischemia or hemorrhage. Previous studies have evaluated the clinical importance of nutritional interventions such as vitamin B supplementation in the management of acute strokes. However, it is still inconclusive whether or not vitamin B supplementation will benefit patients with acute strokes. Therefore, a meta-analysis was performed to assess the efficacy of vitamin B supplementation in the treatment of stroke patients. Medline, Embase, Scopus, and Cochrane Library databases were searched (from 1960 to June 2015) and forest plots were generated to illustrate the treatment effects. A systemic review of the electronic databases yielded 12 eligible studies consisting of 7474 patients. Forest plots from the meta-analyses of the included studies illustrated that vitamin B supplementation significantly lowered the plasma concentration of total homocysteine (SMD = -0.82; 95% CI: -0.77; Z = -29.06, p < 0.0001) and resulted in significant reduction in stroke recurrence (OR = 0.86%; 95% CI: 0.76, 0.97; Z = -2.41; p = 0.016) as well as a combined incidence of vascular events, including recurrent strokes, myocardial infarctions and vascular deaths (OR = 0.87%; 95% CI: 0.79, 0.96; Z= -2.73; p = 0.0063). Additionally, the nearly-symmetrical funnel plot (Egger’s test, t = −1.705, p = 0.1224) indicated the absence of publication bias regarding the meta-analysis that examined the effect of vitamin B supplementation on the plasma levels of homocysteine in acute stroke patients. These findings suggested that vitamin B supplementation presents a potential addition to the armamentarium for the management of acute stroke patients.