Overexpression of α5β1 integrin and angiopoietin-1 co-operatively promote blood-brain barrier integrity and angiogenesis following ischemic stroke.

Overexpression of α5β1 integrin and angiopoietin-1 co-operatively promote blood-brain barrier integrity and angiogenesis following ischemic stroke. Exp Neurol. 2019 Aug 21;:113042 Authors: Wang L, Zhang X, Liu X, Feng G, Fu Y, Milner R, Li L Abstract We previously demonstrated that cross-talk between α5β1 integrin and the angiopoietin-1 (Ang1) / Tie2 receptor plays an important role in regulating brain endothelial angiogenic responses in the ischemic penumbra following cerebral ischemic stroke (CIS). However, a recent study suggested that stimulation of the α5β1 integrin also has the potential of increasing blood-brain barrier (BBB) permeability after CIS, raising doubt about whether α5β1 integrin stimulation by itself will protect against ischemic injury. In light of these conflicting roles, the goal of this study was to evaluate the impact of co-overexpression of α5 integrin and Ang1 on vascular remodeling and repair under cerebral ischemic conditions both in vivo following 90 min of ischemia by temporary occlusion of the middle cerebral artery, and in vitro. Our results demonstrate that as compared to mock-transfected controls, overexpression of α5 integrin alone didn't improve the outcomes in neurological score and size of infarct and caused worse BBB breakdown in the ischemic hemisphere, offsetting its beneficial angiogenic effects during the early stages of CIS. However, co-overexpression of...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research

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Ischemic stroke causes blood–brain barrier (BBB) breakdown due to significant damage to the integrity of BBB components. Recent studies have highlighted the importance of pericytes in the repair process of BBB functions triggered by PDGFRβ up-regulation. Here, we show that perlecan, a major heparan sulfate proteoglycan of basement membranes, aids in BBB maintenance and repair through pericyte interactions. Using a transient middle cerebral artery occlusion model, we found larger infarct volumes and more BBB leakage in conditional perlecan (Hspg2)-deficient (Hspg2–/–-TG) mice than in control mice. Con...
Source: Journal of Cell Biology - Category: Cytology Authors: Tags: Disease, Cell Signaling, Migration, Motility, Neuroscience Articles Source Type: research
Publication date: Available online 5 October 2019Source: Neurochemistry InternationalAuthor(s): Yuxue Chen, Yeye Tian, Hao Tian, Qibo Huang, Yongkang Fang, Wei Wang, Yue Wan, Dengji Pan, Minjie XieAbstractCerebral white matter lesions (WMLs) induced by chronic cerebral hypoperfusion are one of the major components of stroke pathology and closely associated with cognitive impairment. However, the repair and related pathophysiology of white matter after brain injury remains relatively elusive and underexplored. Successful neuroregeneration is a method for the potential treatment of CNS disorders. A non-steroidal estrogen rec...
Source: Neurochemistry International - Category: Neuroscience Source Type: research
In conclusion, older adults exhibited decreased markers of UPR activation and reduced coordination with autophagy and SC-associated gene transcripts following a single bout of unaccustomed resistance exercise. In contrast, young adults demonstrated strong coordination between UPR genes and key regulatory gene transcripts associated with autophagy and SC differentiation in skeletal muscle post-exercise. Taken together, the present findings suggest a potential age-related impairment in the post-exercise transcriptional response that supports activation of the UPR and coordination with other exercise responsive pathways (i.e....
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
The authors of today's research report on success in use of a gene therapy to convert glial cells into neurons in a living mouse brain, and thereby improve the normally limited recovery that takes place following brain injury, such as that caused by a stroke. A number of research groups are investigating this class of approach to enhance regeneration in the brain, an organ that has little capacity to repair itself. The capacity that does exist is generated by neural stem cells that, arguably, continue to produce new neurons at some pace throughout life. As for all stem cell populations, activity declines with age, however....
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
In this study, we report the effects of short-term preconditioning of hMSCs via three-dimensional (3D) aggregation on stroke lesion recovery after intra-arterial (IA) transplantation of 3D aggregate-derived hMSCs (Agg-D hMSCs) in a transient middle cerebral artery occlusion (MCAO) stroke model. Compared with two-dimensional (2D) monolayer culture, Agg-D hMSCs exhibited increased resistance to ischemic stress, secretory function and therapeutic outcome. Short-term preconditioning via 3D aggregation reconfigured hMSC energy metabolism and altered redox cycle, which activated the PI3K/AKT pathway and enhanced resistance to in...
Source: Cytotherapy - Category: Cytology Source Type: research
In this study, researchers studied 438,952 participants in the UK Biobank, who had a total of 24,980 major coronary events - defined as the first occurrence of non-fatal heart attack, ischaemic stroke, or death due to coronary heart disease. They used an approach called Mendelian randomisation, which uses naturally occurring genetic differences to randomly divide the participants into groups, mimicking the effects of running a clinical trial. People with genes associated with lower blood pressure, lower LDL cholesterol, and a combination of both were put into different groups, and compared against those without thes...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Publication date: Available online 10 September 2019Source: Neuroscience LettersAuthor(s): Tapatee Das, Kalyani Soren, Mounica Yerasi, Arvind Kumar, Sumana ChakravartyAbstractFunctional recovery from hypoxia-ischemia depends on an individual’s response to the ischemic damage and recovery. Many of the neurological disorders, including cerebral stroke have sex-specific characteristics. Deciphering the differential molecular mechanisms of sex-specific recovery from hypoxic-ischemic insult can improve medical practice in the treatment of cerebral stroke. In the present study, we describe the establishment of a sex-specif...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research
Condition:   Stroke, Acute Intervention:   Device: OTR4132MD Sponsors:   Organ, Tissue, Regeneration, Repair and Replacement;   European Commission;   EURAXI Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
As one of the major causes of mortality and disability worldwide, ischemic stroke has never been received enough attention. Following ischemia/reperfusion injury, long non-coding RNAs have been extensively found to be involved into inflammatory responses, microvascular endothelial cell death, and angiogenesis in the brain. The small nucleolar RNA host gene 12 was found to be significantly increased following transient middle cerebral artery occlusion. However, the effect and underlying mechanism of small nucleolar RNA host gene 12 in ischemic stroke remain to be explored. We established an oxygen-glucose deprivation/reoxyg...
Source: NeuroReport - Category: Neurology Tags: Degeneration and Repair Source Type: research
We report that interleukin-4 (IL-4) promotes oligodendrocyte regeneration and remyelination. IL-4 receptor expression was detected in a variety of glial cells after ischemic brain injury, including oligodendrocyte lineage cells. IL-4 deficiency in knockout mice resulted in greater deterioration of white matter over 14 days after stroke. Consistent with these findings, intranasal delivery of IL-4 nanoparticles after stroke improved white matter integrity and attenuated long-term sensorimotor and cognitive deficits in wild-type mice, as revealed by histological immunostaining, electron microscopy, diffusion tensor imaging, a...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Rattus norvegicus Source Type: research
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