Silencing of IncRNA XLOC_035088 Protects Middle Cerebral Artery Occlusion-Induced Ischemic Stroke by Notch1 Signaling

Ischemic stroke represents one of the leading causes of mortality worldwide and especially in developing countries. It is crucial for finding effective therapeutic targets that protect the brain against is-chemic injury. Long noncoding RNAs (lncRNAs) have emerged as major regulators of neurological...

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Bibliographic Details
Published in:Journal of neuropathology and experimental neurology 2021-01, Vol.80 (1), p.60
Main Authors: Chen, Miao, Wang, Feng, Wang, Hairong
Format: Article
Language:English
Subjects:
Brain
Care and treatment
Cellular signal transduction
Cerebral ischemia
Complications and side effects
Genetic aspects
Health aspects
Injuries
Neurological research
Physiological aspects
RNA
Stroke (Disease)
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Summary:Ischemic stroke represents one of the leading causes of mortality worldwide and especially in developing countries. It is crucial for finding effective therapeutic targets that protect the brain against is-chemic injury. Long noncoding RNAs (lncRNAs) have emerged as major regulators of neurological diseases, and clarifying their roles in cerebral ischemic injury may provide novel targets for the treatment of ischemic stroke. We aimed to investigate the role of lncRNA-XLOC_035088 in middle cerebral artery occlusion (MCAO)-induced rat brain injury and oxygen-glucose deprivation (OGD)-reperfusion treated hippocampal neurons. in our findings, we found that XLOC 035088 expression was significantly upregu-lated in OGD-reperfusion treated hippocampal neurons and in different brain regions of MCAO-treated rats. XLOC 035088 silencing protected against MCAO-induced ischemic brain injury in vivo and OGD-induced hippocampal neuronal apoptosis in vitro. Intrahippo-campal silencing of XLOC 035088 significantly decreased brain XLOC 035088 expression, reduced brain infarct size, and improved neurological function through inhibiting NOTCH1 following derepression of presenilin 2 (PSEN2). Taken together, this study provides evidence that the lncRNA XLOC_035088/PSEN2/Notch1 axis is involved in the pathogenesis of ischemic brain injury, and presents a promising therapeutic route for ischemic stroke. Key Words: Ischemic stroke, Long noncoding RNA, Middle cerebral artery, Occlusion, XLOC_035088.
ISSN:0022-3069
DOI:10.1093/jnen/nlaa129