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.com
Volume 6
Journal of Neurological Disorders
ISSN: 2329-6895
CNS 2018
November 12-13, 2018
November 12-13, 2018 | Edinburgh, Scotland
4
th
International Conference on
Central Nervous System Disorders & Therapeutics
Increased miR-21-3p in injured brain microvascular endothelial cells following traumatic brain
injury aggravates blood-brain barrier damage by promoting inflammation and apoptosis through
targeting
MAT2B
Xintong Ge
Tianjin Medical University, China
O
ur previous researches have reported that increased miR-21-5p in brain following traumatic brain injury (TBI) could
improve the neurological outcome through alleviating blood-brain barrier (BBB) damage. miR-21-3p is another mature
miRNA derived from pre-miR-21 after dicer procession other than miR-21-5p. Its roles in various diseases, such as tumors
and myocardial disease aroused great interest for research in recent years. To further explore the function and underlying
mechanism of miR-21, especially miR-21-3p in regulating the pathological development of BBB damage after TBI, we
recently focused on studying the impact of miR-21-3p on apoptosis and inflammation in brain microvascular endothelial cells
(BMVECs), the major cellular component of BBB. We performed controlled cortical impact on mouse brain, and employed
the oxygen glucose deprivation/reoxygenation (OGD)-treated bEnd.3 cells injury model. We found that miR-21-3p level in
BMVECs from injured cerebral cortex of controlled cortical impact (CCI) mice, and bEnd.3 cells with OGD treatment were
both increased after injury. For
in vitro
experiments, downregulation on miR-21-3p level by transfecting miR-21-3p antagomir
in cultured cells alleviated OGD-induced BBB damage, characterized by decreased BBB leakage and increased expression of
tight junction proteins. Besides, miR-21-3p antagomir could control inflammatory response by inhibiting the activity of NF-
κB signaling, and suppress cell death by anti-apoptosis. Using luciferase reporter assay and a
MAT2B
-silenced shRNA vector,
we further proved that miR-21-3p exerted above functions through targeting
MAT2B
. In addition,
in vivo
experiments also
confirmed that intracerebroventricular infusion of miR-21-3p antagomir could alleviate BBB leakage after TBI. It reduced
Evans blue extravasation and promoted the expression of tight junction proteins, thus contributed to improve the neurological
outcome of CCI mice. Taken together, increased miR-21-3p in BMVECs after TBI was bad for restoration of injured BBB.
Downregulation on miR-21-3p level in injured brain could be a promising therapeutic strategy for BBB damage after TBI.
gexintongbob@163.comJ Neurol Disord 2018, Volume 6
DOI: 10.4172/2329-6895-C9-050