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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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Clinical Impact: Digital subtraction angiography (DSA) has traditionally been considered an effective method for visualizing carotid free-floating thrombus (CFFT), but it falls short in providing detailed structures of the lumen and the composition of thrombi, making it challenging to determine the etiology. Intravascular optical coherence tomography (OCT) is a valuable adjunct to DSA that can precisely evaluate the characteristics of the intrinsic vessel wall and accurately distinguish between red and white thrombus, providing clues to the etiology of CFFTs. Moreover, OCT not only precisely determined the scope of a floating thrombus but also provided guidance for decision-making in endovascular treatment., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Situs inversus (SI) is a rare congenital anomaly in which systemic organs and vessels are positioned in a mirror image of their normal positions. An interesting issue regarding individuals with such a condition is whether they also have reversed brain asymmetries. Most of studies on this issue indicate that, similarly to many people with normal visceral alignment, patients with SI have a left hemispheric dominance for language functions., Case Presentation: We report a rare occurrence of anomalous cerebral dominance for language in a patient with complete situs inversus. The right-handed patient developed aphasia after carotid stenting, and brain magnetic resonance imaging showed cerebral infarction in the right parietal lobe., Conclusion: Anomalous cerebral dominance for language and visceral situs inversus in our patient both may result from a single, genetically coded atypicality of developmental gradient., (© 2024. The Author(s).)

Purpose: Small dense low-density lipoprotein cholesterol (S-LDL-C) has been suggested as a particularly atherogenic factor for ischemic stroke (IS) in observational studies, but the causality regarding the etiological subtype remains unclear. This study aims to explore the causal effects of small dense low-density lipoprotein cholesterol (S-LDL-C), medium (M-LDL-C) and large (L-LDL-C) subfractions on the lifetime risk of ischemic stroke (IS) and main subtypes using two-sample Mendelian randomization (TSMR) design., Methods: We identified genetic instruments for S-LDL-C, M-LDL-C and L-LDL-C from a genome-wide association study of 115 082 UK Biobank participants. Summary-level data for genetic association of any ischemic stroke (AIS), large artery stroke (LAS), small vessel stroke (SVS) and cardioembolic stroke (CES) were obtained from MEGASTROKE consortium. Accounting for the pleiotropic effects of triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C), we conducted multivariable TSMR analysis., Results: In univariable TSMR, we found a causal association between genetically predicted S-LDL-C and LAS (IVW-FE: odds ratio (OR) = 1.481, 95% confidence interval (CI): 1.117-1.963, P = 0.006, q = 0.076) but not AIS, SVS or CES. No causal effects were observed for M-LDL-C or L-LDL-C in terms of AIS and IS subtype. In multivariable analysis, the causal association between S-LDL-C and LAS remained significant (IVE-MRE: OR = 1.329, 95% CI: 1.106-1.597, P = 0.002)., Conclusions: Findings supported a causal association between S-LDL-C and LAS. Further studies are warranted to elucidate the underlying mechanism and clinical benefit of targeting S-LDL-C., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer Y-XC declared a shared affiliation with the author PL to the handling editor at the time of the review., (Copyright © 2024 Yu, Shen, Zhang, Cui, Zha, Li, Li, Wang and Nan.)

Background: Bow Hunter's syndrome (BHS), also known as rotational vertebral artery occlusion (RVAO), is a rare condition characterized by dynamic vertebrobasilar insufficiency due to position-dependent occlusion of the vertebral artery (VA). In the existing literature, most cases of BHS are attributed to osteophytic compression originating from the occipital condyle or within the transverse foramen, often accompanied by anatomical abnormalities of the VA. However, cases presenting solely with VA anomalies in the absence of any cervical vertebral structural abnormality are rare. This case report presents a unique instance of BHS in a 56-year-old male, attributed to the anomalous origin of the right VA and the absence of the left VA, without cervical structural abnormalities., Case Presentation: The patient exhibited symptoms like episodic dizziness and vertigo, which were exacerbated by rightward head rotation and alleviated upon returning to a neutral position. Diagnostic evaluation, including digital subtraction angiography, revealed that the right VA originated from the right common carotid artery and compression-induced stenosis of the right VA during head rotation. Conservative management, including avoidance of certain head movements and anti-arteriosclerosis medication, led to symptom resolution over a two-year follow-up period., Conclusions: This report contributes to the understanding of BHS by highlighting a rare vascular anomaly presentation and incorporates a review of 14 similar case reports in the literature describing that an anatomical abnormality of the VA is mainly responsible for the pathology of BHS in the absence of cervical vertebral anomalies, thus emphasizing the need for careful diagnostic and management strategies., (© 2024. The Author(s).)

Competing Interests: Disclosures None.

Competing Interests: Disclosures None.

Background: The role of endovascular therapy for acute stroke with a large infarction has not been extensively studied in differing populations., Methods: We conducted a multicenter, prospective, open-label, randomized trial in China involving patients with acute large-vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower values indicating larger infarction) or an infarct-core volume of 70 to 100 ml. Patients were randomly assigned in a 1:1 ratio within 24 hours from the time they were last known to be well to undergo endovascular therapy and receive medical management or to receive medical management alone. The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability), and the primary objective was to determine whether a shift in the distribution of the scores on the modified Rankin scale at 90 days had occurred between the two groups. Secondary outcomes included scores of 0 to 2 and 0 to 3 on the modified Rankin scale. The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours after randomization., Results: A total of 456 patients were enrolled; 231 were assigned to the endovascular-therapy group and 225 to the medical-management group. Approximately 28% of the patients in both groups received intravenous thrombolysis. The trial was stopped early owing to the efficacy of endovascular therapy after the second interim analysis. At 90 days, a shift in the distribution of scores on the modified Rankin scale toward better outcomes was observed in favor of endovascular therapy over medical management alone (generalized odds ratio, 1.37; 95% confidence interval, 1.11 to 1.69; P = 0.004). Symptomatic intracranial hemorrhage occurred in 14 of 230 patients (6.1%) in the endovascular-therapy group and in 6 of 225 patients (2.7%) in the medical-management group; any intracranial hemorrhage occurred in 113 (49.1%) and 39 (17.3%), respectively. Results for the secondary outcomes generally supported those of the primary analysis., Conclusions: In a trial conducted in China, patients with large cerebral infarctions had better outcomes with endovascular therapy administered within 24 hours than with medical management alone but had more intracranial hemorrhages. (Funded by Covidien Healthcare International Trading [Shanghai] and others; ANGEL-ASPECT ClinicalTrials.gov number, NCT04551664.)., (Copyright © 2023 Massachusetts Medical Society.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Ischemic stroke (IS) is the leading cause of disability and death worldwide. Owing to the aging population and unhealthy lifestyles, the incidence of cerebrovascular disease is high. Vascular risk factors include hypertension, diabetes, dyslipidemia, and obesity. Therefore, in addition to timely and effective reperfusion therapy for IS, it is crucial to actively control these risk factors to reduce the incidence and recurrence rates of IS. Evidence from human and animal studies suggests that moderate intermittent hypoxia (IH) exposure is a promising therapeutic strategy to ameliorate common vascular risk factors and comorbidities. Given the complex pathophysiological mechanisms underlying IS, effective treatment must focus on reducing injury in the acute phase and promoting repair in the recovery phase. Therefore, this review discusses the preclinical perspectives on IH conditioning as a potential treatment for neurovascular injury and highlights IH pre and postconditioning strategies for IS. Hypoxia conditioning reduces brain injury by increasing resistance to acute ischemic and hypoxic stress, exerting neuroprotective effects, and promoting post-injury repair and regeneration. However, whether IH produces beneficial effects depends not only on the hypoxic regimen but also on inter-subject differences. Therefore, we discuss the factors that may influence the effectiveness of IH treatment, including age, sex, comorbidities, and circadian rhythm, which can be used to help identify the optimal intervention population and treatment protocols for more accurate, individualized clinical translation. In conclusion, IH conditioning as a non-invasive, non-pharmacological, systemic, and multi-targeted intervention can not only reduce brain damage after stroke but can also be applied to the prevention and functional recovery of IS, providing brain protection at different stages of the disease. It represents a promising therapeutic strategy. For patients with IS and high-risk groups, IH conditioning is expected to develop as an adjunctive clinical treatment option to reduce the incidence, recurrence, disability, and mortality of IS and to reduce disease burden., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yuan, Liu, Gu, Ji and Nan.)

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 <120 mm Hg) or less intensive treatment (target 140-180 mm Hg) to be achieved within 1 h and sustained for 72 h. The primary efficacy outcome was functional recovery, assessed according to the distribution in scores on the modified Rankin scale (range 0 [no symptoms] to 6 [death]) at 90 days. Analyses were done according to the modified intention-to-treat principle. Efficacy analyses were performed with proportional odds logistic regression with adjustment for treatment allocation as a fixed effect, site as a random effect, and baseline prognostic factors, and included all randomly assigned patients who provided consent and had available data for the primary outcome. The safety analysis included all randomly assigned patients. The treatment effects were expressed as odds ratios (ORs). This trial is registered at ClinicalTrials.gov, NCT04140110, and the Chinese Clinical Trial Registry, 1900027785; recruitment has stopped at all participating centres., Findings: Between July 20, 2020, and March 7, 2022, 821 patients were randomly assigned. The trial was stopped after review of the outcome data on June 22, 2022, due to persistent efficacy and safety concerns. 407 participants were assigned to the more intensive treatment group and 409 to the less intensive treatment group, of whom 404 patients in the more intensive treatment group and 406 patients in the less intensive treatment group had primary outcome data available. The likelihood of poor functional outcome was greater in the more intensive treatment group than the less intensive treatment group (common OR 1·37 [95% CI 1·07-1·76]). Compared with the less intensive treatment group, the more intensive treatment group had more early neurological deterioration (common OR 1·53 [95% 1·18-1·97]) and major disability at 90 days (OR 2·07 [95% CI 1·47-2·93]) but there were no significant differences in symptomatic intracerebral haemorrhage. There were no significant differences in serious adverse events or mortality between groups., Interpretation: Intensive control of systolic blood pressure to lower than 120 mm Hg should be avoided to prevent compromising the functional recovery of patients who have received endovascular thrombectomy for acute ischaemic stroke due to intracranial large-vessel occlusion., Funding: The Shanghai Hospital Development Center; National Health and Medical Research Council of Australia; Medical Research Futures Fund of Australia; China Stroke Prevention; Shanghai Changhai Hospital, Science and Technology Commission of Shanghai Municipality; Takeda China; Hasten Biopharmaceutic; Genesis Medtech; Penumbra., Competing Interests: Declaration of interests PY reports funding from Shanghai Changhai Hospital and honoraria for lectures from Stryker, Medtronic, Microvention, and Cerenovus. LS reports grants and speaker fees from Takeda China. CM reports grants from the Dutch Heart Foundation, the European Commission, Stryker, and Healthcare Evaluation Netherlands. MG reports grants from NoNo, Medtronic, and Cerenovus; and consulting fees from Medtronic, Microvention, Stryker, and Mentice; and is the inventor and receives royalties for a novel imaging system for the diagnosis of acute ischaemic stroke (GE Healthcare systems licensing agreement; patents US9324143 and US 9486176) and a device for accessing intracranial vessels (Microvention licensing agreement; US 10,456,552). Jianmin Liu reports grants from the China Stroke Prevention Project and the Science and Technology Commission of Shanghai Municipality. CSA reports grants from the National Health and Medical Research Council (NHMRC) and Medical Research Futures Fund (MRFF) of Australia, the UK Medical Research Council, Penumbra, and Takeda China; and is a board member for the World Stroke Organisation and the Editor-in-Chief of Cerebrovascular Disease. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Mechanical 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., Methods: This 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., Results: A 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., Conclusion: Endovascular 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%)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Ischemic stroke is associated with increasing morbidity and has become the main cause of death and disability worldwide. Cerebral edema is a serious complication arising from ischemic stroke. It causes an increase in intracranial pressure, rapid deterioration of neurological symptoms, and formation of cerebral hernia, and is an important risk factor for adverse outcomes after stroke. To date, the detailed mechanism of cerebral edema after stroke remains unclear. This limits advances in prevention and treatment strategies as well as drug development. This review discusses the classification and pathological characteristics of cerebral edema, the possible relationship of the development of cerebral edema after ischemic stroke with aquaporin 4, the SUR1-TRPM4 channel, matrix metalloproteinase 9, microRNA, cerebral venous reflux, inflammatory reactions, and cerebral ischemia/reperfusion injury. It also summarizes research on new therapeutic drugs for post-stroke cerebral edema. Thus, this review provides a reference for further studies and for clinical treatment of cerebral edema after ischemic stroke., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gu, Zhou, Piao, Yuan, Jiang, Wei, Zhou, Nan and Ji.)

Competing Interests: Competing interests: None declared.

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., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Introduction: A recent clinical study revealed that Ninjin'yoeito (NYT) may potentially improve cognitive outcome. However, the mechanism by which NYT exerts its effect on elderly patients remains unclear. The aim of this study is to evaluate the effect of Ninjin'yoeito on regional brain glucose metabolism by 18 F-FDG autoradiography with insulin loading in aged wild-type mice. Materials and Methods: After 12 weeks of feeding NYT, mice were assigned to the control and insulin-loaded groups and received an intraperitoneal injection of human insulin (2 U/kg body weight) 30 min prior to 18 F-FDG injection. Ninety minutes after the injection, brain autoradiography was performed. Results: After insulin loading, the 18 F-FDG accumulation showed negative changes in the cortex, striatum, thalamus, and hippocampus in the control group, whereas positive changes were observed in the NYT-treated group. Conclusions: Ninjin'yoeito may potentially reduce insulin resistance in the brain regions in aged mice, thereby preventing age-related brain diseases., Competing Interests: RI and YO were employed by the company Tsumura & Co. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhao, Imai, Ukon, Shimoyama, Tan, Maejima, Omiya, Takahashi, Nan, Zhao, Ito and Shimomura.)

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. [ 18 F]-Fluoro-2-deoxy-2-D-glucose ( 18 F-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 18 F-FDG accumulation and 18 F-FDG autoradiography with insulin loading in aged and young wild-type mice. In the untreated groups, the levels of 18 F-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 18 F-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 18 F-FDG accumulation levels were observed in those in the young mice. These results demonstrate that insulin loading decreases effect on 18 F-FDG accumulation levels in some organs of the aged mice. Therefore, aging can increase insulin resistance and lead to systemic glucose metabolism dysfunction.

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., (Copyright © 2020 Sun, Xu, Zhang, He, Liu, Liu and Nan.)

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., (Copyright Journal of Radiology Case Reports.)

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., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

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.

Rationale: Neurocysticercosis (NCC) can cause lesions across the central nervous system, leading to varying clinical manifestations. While the presentation of nonspecific symptom is rare, they are easy to ignore. The present report documents a case of NCC that manifested as persistent dizziness., Patient Concerns: A Chinese woman visited the hospital on account of dizziness, the severity of which had increased gradually over the month prior., Diagnoses: Head computed tomography and magnetic resonance imaging (MRI) revealed hydrocephalus. Cervical MRI revealed an abnormal object in the spinal canal at the junction of the medulla oblongata and C1, which blocked the circulation cerebrospinal fluid circulation and caused the enlargement of the ventricles., Intervention: The patient underwent surgical treatment. The abnormal object was removed, and a diagnosis of NCC was considered by pathological examination., Outcome: The patient's dizziness resolved after surgical treatment, and no other symptoms appeared thereafter., Lesson: Clinicians should not ignore nonspecific clinical symptoms, as they may indicate hydrocephalus.

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.

Rationale: Multifocal cerebral hemorrhage refers to the cerebral hemorrhage in 2 or more lesions at the same time or 48 h in the brain caused by various causes, which has an acute onset, high mortality rate, and poor clinical treatment effect. Subarachnoid hemorrhage (SAH) is caused by the direct flow of blood into the subarachnoid cavity due to the rupture of the diseased vessels at the base or surface of the brain. Cerebral venous sinus thrombosis (CVST) affects approximately 5 people per million and accounts for approximately 1% of all stroke events. CVST with both SAH and multifocal intracerebral hemorrhage (ICH) as the first presentation is extremely rare., Patient Concerns: A 57-year-old woman presented with dizziness, nausea, and vomiting., Diagnosis: Neuroimaging confirmed a diagnosis of CVST., Interventions: The patient was treated with dehydration, scavenging free radicals, and nerve protection therapy., Outcomes: After 4 weeks of systematic treatment, the patient resumed independent daily activities and was discharged with only slight non-fluent aphasia. She did not exhibit recurrent thrombosis at an 18-month follow-up point., Main Lessons: The usual treatment for sinus thrombosis is anticoagulation or local thrombolysis. Systemic anticoagulation is the first-line treatment for CVST, even in patients with cerebral hemorrhage or SAH. The present patient's hemorrhage clearly contraindicated heparin; therefore, no anticoagulants or thrombolytic agents were administered during the 4-week hospitalization. We discuss issues for consideration in similar cases and provide an example of determining an individualized approach to treatment.

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.

Background: Evidence for the preventative effects of percutaneous transluminal angioplasty and stenting (PTAS) on the recurrence of stroke in patients with severe intracranial vertebrobasilar stenoses (IVBS) varies, and the influence of study characteristics on the study outcomes have not been determined., Methods: A study level based meta-analysis was performed to investigate the influence of baseline characteristics on the 30-day and follow-up stroke recurrence or death in symptomatic IVBS patients receiving PTAS. Relevant single center studies were retrieved by searching PubMed and Embase. A random effect model was applied to synthesize the outcomes. Meta-regression and subgroup analyses were performed to evaluate the potential influence of study characteristics on outcomes., Results: Fifteen cohort studies comprising 554 symptomatic IVBS patients were included. PTAS was associated with an 8% incidence of stroke recurrence or death (95% CI: 5% to 12%) in IVBS patients within 30 days, and 8 per 100 person-years (95% CI: 5 to 11 per 100 person-years) of cumulative stroke recurrence or death during follow-up. Meta-regression indicated that the center volume, as defined by the numbers of cases per year, was negatively correlated with 30-day (regression coefficient = -0.09, p = 0.02) and follow-up (regression coefficient = -0.60, p = 0.01) stroke recurrence or death. Age, gender, or comorbidities have no significant effect on the outcomes., Conclusions: Centers of higher procedural volume may be associated with better clinical outcomes for symptomatic IVBS patients receiving PTAS., Competing Interests: The authors have declared that no competing interests exist.

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.

Rationale: Mild-to-moderate alcoholic cirrhosis of the liver is related to spontaneous intracerebral hemorrhage (ICH). In terms of spontaneous brainstem hemorrhage, pontine is considered as the most common site in contrast to medulla oblongata where the hemorrhage is rarely seen. This rare primary medullary hemorrhage has been attributed so far to vascular malformation (VM), anticoagulants, hypertension, hemorrhagic transformation, and other undetermined factors., Patient Concerns: Herein, we describe a 53-year-old patient with 35-year history of alcohol abuse was admitted for acute-onset isolated hemianesthesia on the right side. He was normotensive on admission. A neurological examination revealed isolated hemihypoaesthesia on the right side. He had no history of hypertension, and viral hepatitis, and nil use of anticoagulants., Diagnoses: Brain computed tomography (CT) image demonstrated hemorrhagic lesion in dorsal and medial medulla oblongata which was ruptured into the fourth ventricle. Brain magnetic resonance imaging (MRI), and magnetic resonance angiography (MRA) demonstrated no evidence of VM. The laboratory tests implied liver dysfunction, thrombocytopenia, and coagulation disorders. Abdominal ultrasound, and CT image showed a small, and nodular liver with splenomegaly, suggestive of moderate alcoholic cirrhosis., Interventions: Liver protection therapy and the management of coagulation disorders., Outcomes: After 14 days, he was discharged with mild hemianesthesia but with more improved parameters in laboratory tests. At the 6-month follow-up, brain MRI, MRA, and non-contrast MRI showed no significant findings except for a malacic lesion., Lessons: We conclude that the patient had alcoholic cirrhosis with coagulopathy, and this may have resulted in primary medullary hemorrhage. This is a first case to report alcoholic cirrhosis as etiology of primary medullary hemorrhage.

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., (Copyright © 2017. Published by Elsevier Inc.)

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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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.

The present case report described a patient with thrombotic thrombocytopenic purpura (TTP), who presented to the China-Japan Union Hospital of Jilin University (Changchun, China), and the changes in plasma von Willebrand factor (vWF) and vWF cleaving protease (vWF-cp) observed during treatment. Computed tomography and diffusion-weighted magnetic resonance (MR) imaging of the brain, cerebral MR angiography and other experimental tests were performed and the patient was subsequently diagnosed with TTP. The patient underwent treatment with plasma exchange, glucocorticoids and supportive care. Hematologic and biochemical parameters began to gradually improve over the 12 days after admission; platelet count, serum creatinine and serum lactate dehydrogenase concentrations returned to their normal ranges, plasma vWF concentration decreased to normal levels over the 30 days after admission, and vWF-cp activity increased compared with the levels detected in healthy volunteers. Monthly rituximab treatment was administered 4 times following patient discharge to prevent relapse, and no recurrence was detected at the 20-month follow-up. Plasma exchange therapy is effective in patients with TTP. After low-dose rituximab treatment, recurrent TTP has not been detected found till now. In the present case, vWF concentration and vWF-cp activity were measured at 8, 10, 23 and 32 days after admission; compared with the control group, patient's vWF concentration gradually decreased and vWF-cp activity slowly increased, suggesting that the patient had a favorable prognosis and a low risk of recurrence.

The pathogenesis of vascular dementia (VD) is associated with neuronal degeneration, apoptosis or necrosis following ischemic brain injury. L‑butylphthalide (L‑NBP), has been demonstrated to exhibit potent anti‑ischemic and anti‑VD effects, however the associated specific mechanism remains to be elucidated. The present study generated a VD rat model, in which the effect of L‑NBP on neurological function and expression levels of brain‑derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB) were observed. A total of 90 male Sprague Dawley rats were randomly divided into sham, model and L‑NBP groups (n=30). The VD model was generated by ligation of bilateral common carotid artery. A Morris water maze was used to test learning and memory functions. Animals were then sacrificed and cortical and hippocampal tissues were extracted. Hematoxylin and Eosin staining was used to observe brain tissue injury, and reverse transcription‑quantitative polymerase chain reaction was employed to measure BDNF and TrkB mRNA levels. Western blotting was employed to measure BDNF, TrkB and serine‑threonine protein kinase (Akt) protein levels. Immunohistochemistry staining was used to detect the N‑methyl‑D‑aspartate receptor (NMDAR) levels. VD rats exhibited elongated escape latency and lower crossing times, with significant neuronal damage. L‑NBP treatment shortened escape latency, increased crossing times and improved cortical and hippocampal injury. BDNF, TrkB, Akt and NMDAR expressions in the treatment group were significantly increased compared with the model group (P<0.05). L‑NBP may therefore enhance hippocampal expression of BDNF, TrkB, Akt and NMDAR, decrease ischemic injury of VD rats, and improve learning and memory.

Rationale: Intracranial vascular atherosclerotic occlusion is one of the most common causes of ischemic stroke world wide. The involvement of large intracranial vessels, in particular, the middle cerebral artery, is usually associated with unfavorable outcomes in patients. Spontaneous recanalization of atherosclerotic occlusion is relatively rare., Patient Concerns: The first patient was a 43-year-old male with slurred speech and left-sided weakness for a duration of 24 hours. The second was a 59-year-old male with left-sided weakness over a period of 13 hours. The last was a 49-year-old female patient presented with a 1-month history of right-sided headache., Diagnoses: Atherosclerotic middle cerebral artery occlusion., Interventions: In all cases, oral aspirin (100 mg; once daily), Plavix (75 mg; once daily), and Lipitor (40 mg; once daily) were used . Oral Plavix was stopped 3 months., Outcomes: Spontaneous recanalization occured in the three cases of atherosclerotic middle cerebral artery occlusion., Lessons: Spontaneous recanalization may occur in both early and late stages of atherosclerotic middle cerebral artery occlusion. Clinicians should be aware of this particular condition, as it may represent a relatively favorable prognosis.

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.

Background: Myoclonus is a clinical sign characterized by sudden, brief jerky, shock-like involuntary movements of a muscle or group of muscles. Dystonia is defined as a syndrome of sustained muscle contractions, frequently causing twisting and repetitive movements or abnormal postures. Cases of myoclonus or dystonia secondary to a structural lesion in the cerebellum have been reported. However, there has never been a reported case of combined myoclonus and dystonia secondary to a cerebellar lesion., Case Presentation: Herein, we report a 22-year-old female patient with sudden-onset myoclonic jerks, dystonic posture and mild ataxia in the right upper extremity. At age 19, she experienced sudden headache with vomiting. The neurological examination showed ataxia, myoclonus and dystonia in the right upper extremity. Brain images demonstrated a hemorrhage in the right cerebellar hemisphere secondary to a cavernous malformation. After resection of the hemorrhagic mass, headache with vomiting disappeared and ataxia improved, but myoclonus and dystonia persisted., Conclusions: It is the first report of combined focal myoclonus and dystonia secondary to a cerebellar lesion.

Protein kinases are critical modulators of a variety of intracellular and extracellular signal transduction pathways, and abnormal phosphorylation events can contribute to disease progression in a variety of diseases. As a result, protein kinases have emerged as important new drug targets for small molecule therapeutics. The mitogen-activated protein kinase (MAPK) signaling pathway transmits signals from the cell membrane to the nucleus in response to a variety of different stimuli. Because this pathway controls a broad spectrum of cellular processes, including growth, inflammation, and stress responses, it is accepted as a therapeutic target for cancer and peripheral inflammatory disorders. There is also increasing evidence that MAPK is an important regulator of ischemic and hemorrhagic cerebral vascular disease, raising the possibility that it might be a drug discovery target for stroke. In this review, we discuss the MAPK signaling pathway in association with its activation in stroke-induced brain injury.

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.

Staphylococcus aureus is a common pathogen that causes a wide range of infectious diseases. The function of TLRs, specifically TLR2, during S. aureus infection is still debated. In this study, we investigated the extent to which TLR2 contributes to the host innate response against the bacterial infection using TLR2-deficient mice. Intravenous inoculation with S. aureus resulted in all TLR2-deficient mice dying within 4 d, along with a high bacterial burden in the livers. However, histological examination showed the same degree of macrophage and neutrophil accumulation in the livers of infected TLR2-deficient mice as that in infected wild-type (WT) mice. TLR2-deficient mouse macrophages also showed normal phagocytic activity, although they failed to express CD36 that appeared on the surface of WT mouse cells upon challenge with heat-killed S. aureus. These data indicate that TLR2, as well as CD36, does not directly affect S. aureus clearance and that CD36 expression on macrophages depends on the presence of TLR2. In vivo infection with S. aureus caused significantly elevated production of TNF-α and IL-6 in the livers and blood of TLR2-deficient mice compared with those in WT mice, while the hepatic and serum levels of IL-10 decreased in these mice. In contrast, lower expression of IL-6 and IL-10, but not of TNF-α, at both the gene and protein levels was found in TLR2-deficient mouse macrophages compared to that in WT mouse cells, in response to challenge with heat-killed S. aureus. These findings suggest that the S. aureus-induced pro-inflammatory cytokine response is not dependent on macrophages and that TLR2 deficiency results in decreased IL-10 release by macrophages, which contributes to dysregulated cytokine balance, impaired bacterial clearance, and mouse death. Therefore, TLR2 possesses a protective function during S. aureus infection by regulating pro- and anti-inflammatory cytokine responses.

PCR amplification and sequencing of whole blood DNA from an individual with hereditary spastic paraplegia, as well as family members, revealed a fragment of proteolipid protein 1 (PLP1) gene exon 1, which excluded the possibility of isomer 1 expression for this family. The fragment sequence of exon 3 and exon 5 was consistent with the proteolipid protein 1 sequence at NCBI. In the proband samples, a PLP1 point mutation in exon 4 was detected at the basic group of position 844, T→C, phenylalanine→leucine. In proband samples from a male cousin, the basic group at position 844 was C, but gene sequencing signals revealed mixed signals of T and C, indicating possible mutation at this locus. Results demonstrated that changes in PLP1 exon 4 amino acids were associated with onset of hereditary spastic paraplegia.