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Focusing on claudin-5: a promising candidate in the regulation of BBB to treat ischemic stroke
Publication date: Available online 5 December 2017 Source:Progress in Neurobiology Author(s): Jianjun Lv, Wei Hu, Zhi Yang, Tian Li, Shuai Jiang, Zhiqiang Ma, Fulin Chen, Yang Yang Claudin-5 is a tight junction (TJ) protein in the blood-brain barrier (BBB) that has recently attracted increased attention. Numerous studies have demonstrated that claudin-5 regulates the integrity and permeability of the BBB. Increased claudin-5 expression plays a neuroprotective role in neurological diseases, particularly in cerebral ischemic stroke. Moreover, claudin-5 might be a potential marker for early hemorrhagic transformation detecti...
Source: Progress in Neurobiology - December 6, 2017 Category: Neuroscience Source Type: research

Microarray Data Analysis of Molecular Mechanism Associated with Stroke Progression
This study aimed to explore the molecular mechanism of stroke and provide a new target in the clinical management. The miRNA dataset GSE97532 (3 blood samples from middle cerebral artery occlusion (MCAO) and 3 from sham operation) and mRNA dataset GSE97533 (3 blood samples from MCAO and 3 from sham operation) were obtained from GEO database. Differentially expressed mRNA (DEGs) and miRNAs (DEMIRs) were screened out between MCAO and sham operation groups. Then, DEMIR –DEG interactions were explored and visualized using Cytoscape software. Moreover, the enrichment analysis was performed on these DEMIRs and DEGs. Furthermor...
Source: Journal of Molecular Neuroscience - January 4, 2019 Category: Neuroscience Source Type: research

Gene therapy of adeno-associated virus (AAV) vectors in preclinical models of ischemic stroke
CNS Neurosci Ther. 2023 Aug 8. doi: 10.1111/cns.14392. Online ahead of print.ABSTRACTStroke has been associated with devastating clinical outcomes, with current treatment strategies proving largely ineffective. Therefore, there is a need to explore alternative treatment options for addressing post-stroke functional deficits. Gene therapy utilizing adeno-associated viruses (AAVs) as a critical gene vector delivering genes to the central nervous system (CNS) gene delivery has emerged as a promising approach for treating various CNS diseases. This review aims to provide an overview of the biological characteristics of AAV vec...
Source: CNS Neuroscience and Therapeutics - August 8, 2023 Category: Neuroscience Authors: Jing Wang Mengna Zhu Jingyi Sun Lina Feng Mingfeng Yang Baoliang Sun Leilei Mao Source Type: research

Hypoxia-controlled matrix metalloproteinase-9 hyperexpression promotes behavioral recovery after ischemia
Abstract Matrix metalloproteinase-9 (MMP-9) plays a beneficial role in the sub-acute phase after ischemic stroke. However, unrestrained MMP-9 may disrupt the blood-brain barrier (BBB), which has limited its use for the treatment of brain ischemia. In the present study, we constructed lentivirus mediated hypoxia-controlled MMP-9 expression and explored its role after stroke. Hypoxia response element (HRE) was used to confine MMP-9 expression only to the hypoxic region of mouse brain after 120-min transient middle cerebral artery occlusion. Lentiviruses were injected into the peri-infarct area on day 7 after transie...
Source: Neuroscience Bulletin - May 14, 2015 Category: Neuroscience Source Type: research

Sulfiredoxin-1 protects primary cultured astrocytes from ischemia-induced damage
In this study, we used oxygen-glucose deprivation followed by recovery (OGD/R) and hydrogen peroxide (H2O2) to mimic stress from cerebral ischemic damage on primary cultured astrocytes. We found that knockdown of Srxn1 by two shRNAs resulted in decreased cell viability of astrocytes. Decreased level of Srxn1 also correlated with excessive levels of proinflammatory cytokines and chemokines such as TNF-α, MPO, IL-1β, and IL-6. In addition, Srxn1 appeared to influence the strength of TLR4 signaling pathway; the expression of COX-2, IL-6, and NOS2 were strongly induced by OGD/R and H2O2 in astrocyte cultures with Srxn1-shRNA...
Source: Neurochemistry International - January 26, 2015 Category: Neuroscience Source Type: research

Autism in the Son of a Woman with Mitochondrial Myopathy and Dysautonomia: A Case Report
Conclusion Given emerging evidence that mitochondrial dysfunction, particularly in the electron transport chain needed for cellular energy production, is an underlying pathophysiological mechanism for some varieties of ASD, clinicians should have a high index of suspicion for mitochondrial disease, especially when they encounter a patient with unusual neurological or constitutional symptoms. The prevalence of mitochondrial disease in ASD patients may be as high as five percent, which means that it is not the “zebra”[27] diagnosis that it might be in a non-ASD patient, where prevalence is about 0.01 percent.10 Reference...
Source: Innovations in Clinical Neuroscience - October 9, 2015 Category: Neuroscience Authors: ICN Online Editor Tags: Anxiety Disorders Asperger's syndrome Autism Behavioral and Cognitive Neurology Case Report Current Issue Intellectual Disability Neurologic Systems and Symptoms Pervasive Developmental Disorders ASD autism spectrum disorder dysauton Source Type: research

Expression of nerve growth factor carried by pseudotyped lentivirus improves neuron survival and cognitive functional recovery of post-ischemia in rats.
CONCLUSION: This study demonstrates a potential β-NGF gene therapy by utilization of pseudolentivirus in ischemia and indicates future applications of NGF gene treatment in ischemic patients. PMID: 29409115 [PubMed - as supplied by publisher]
Source: CNS Neuroscience and Therapeutics - February 6, 2018 Category: Neuroscience Authors: Cao JY, Lin Y, Han YF, Ding SH, Fan YL, Pan YH, Zhao B, Guo QH, Sun WH, Wan JQ, Tong XP Tags: CNS Neurosci Ther Source Type: research

Targeted Gene Therapy for Ischemic Stroke
Exogenous delivery of angiogenic and neuroprotective genes has been shown to enhance innate compensatory responses after ischemic injury. However, there are certain barriers in translating gene-based therapy to the clinical setting. For example, systemic delivery of genes into the brain is prevented by the blood–brain barrier (BBB); intraventricular delivery results in nonspecific distribution and gene expression; and stereotactic injection of vectors into the ischemic penumbra requires an invasive procedure that can cause additional damage. This chapter describes an adeno-associated viral (AAV) vector with two prima...
Source: Springer protocols feed by Neuroscience - January 10, 2015 Category: Neuroscience Source Type: news

Neuroscience is the Next Oncology
by Michael D. Ehlers, MD, PhD Dr. Ehlers is with Biogen in Cambridge, Massachusetts. Innov Clin Neurosci. 2018;15(3–4):15–16 Funding: No funding was received for the preparation of this article. Disclosures: Dr. Ehlers is an employee and shareholder at Biogen Inc. in Cambridge, Massachusetts. Prominent and expensive failures in Alzheimer’s disease therapies have led to a contagious belief system in some parts of the biopharma industry that neuroscience is just too hard, too risky, and too uncertain. But, might this belief system itself be a residual bias of the past? Close inspection reveals all the signs of a coming...
Source: Innovations in Clinical Neuroscience - April 1, 2018 Category: Neuroscience Authors: ICNS Online Editor Tags: Commentary Current Issue Source Type: research

Combined Gene Therapy to Reduce the Neuronal Damage in the Mouse Model of Focal Ischemic Injury
AbstractResearch into stroke is driven by frustration over the limited available therapeutics. Targeting a single aspect of this multifactorial disease contributes to the therapeutic boundaries. To overcome this, we devised a novel multifactorial-cocktail treatment, using lentiviruses encoding excitatory amino acid transporter 2 (EAAT2(, glutamate dehydrogenase 2 (GDH2), and nuclear factor E2-related factor 2 (Nrf2) genes, that acts synergistically to address the effected excito-oxidative axis. Here, we used the vasoconstrictor endothelin-1 (ET-1) to induce focal ischemic injury in mice by direct injection into the striatu...
Source: Journal of Molecular Neuroscience - September 3, 2018 Category: Neuroscience Source Type: research