The Basic Research On The Function And Mechanism Of MiR-21-3p In The Blood-brain Barrier Damage After Traumatic Brain Injury

Traumatic brain injury(TBI)is a significant public health problem in the world.The severity of secondary brain damage is closely related to the prognosis of TBI.The traumatic blood-brain barrier(BBB)damage is an important pathological change in brain after traumatic brain injury(TBI).Our recent papers 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 designed this research and 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 b End.3 cells injury model.We found that miR-21-3p level in BMVECs from injured cerebral cortex of controlled cortical impact(CCI)mice,and b End.3 cells with OGD treatment were both increased after injury.For in-vitroexperiments,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 suppress cell death by anti-apoptosis,and control inflammatory response by inhibiting the activity of NF-κB signaling.Using luciferase reporter assay and a MAT2B-silenced sh RNA vector,we further proved that miR-21-3p exerted above functions through targeting MAT2 B.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.