MicroRNA-103-3p Influence Blood Brain Barrier Integrity And Neurological Function After Subarachnoid Hemorrhage By Targeting Caveolin-1

Objective Subarachnoid hemorrhage (SAH) is associated with high motility and poor sequelae. Blood brain barrier disruption after SAH is the key pathophysiologic process that deteriorating SAH damage. The present study was aimed at investigating whether miR-103-3p influences on blood brain barrier integrity and neurological functions of SAH rats and further exploring the underlying molecular mechanisms.Methods:To study the relationship between miR-103-3p and Caveolin-1, we cultured bEnd.3 cells and performed Dual luciferase report experiments. Then we overexpresed or inhibited miR-103-3p to investigate whether the expressions of Caveolin-1, ZO-1 and Occludin were changed as well. To observe the effects of miR-103-3p inhibitor for SAH, we produced SAH models by the endovascular perforation in rats.60 Male SD rats were divided into three groups: sham operation group, miR-103-3p control group and miR-103-3p antagomir group. We infused miR-103-3p control or miR-103-3p antagomir into Lateral ventricle of rats 24 h before inducing SAH. QPCR and Western blot were used to compare the expression level of miR-103-3p and Cav-1 across groups. Immunohistochemistry technology was used to compare the permeability of BBB. Furthermore, neurological outcomes were measured using the Modified Garcia Score and beam balance test at 1,3,7,14 and 28 d after SAH by a blinded observer.Results miR-103-3p interacted with the 3’UTRs of Caveolin-1 RNA messenger. Changing the expression level of miR-103-3p led to the corresponding changes of Caveolin-1, ZO-1 and Occludin. Compared with sham group, miR-103-3p was increased and Cav-1 was decreased significantly at 6 hr and 24 hr after SAH. After intracerebroventricular infusion of miR-103-3p antagomir, Cav-1, ZO-1 and Occludin expressions were increased and BBB permeability was decreased relative to control group at 24 hr after SAH. Further, the neurological outcomes of SAH rats were improved by miR-103-3p antagomir at 1,3,7,14 and 28 d after SAH.Conclusion miR-103-3p interacts with the 3’UTRs of Caveolin-1 RNA messenger. Inhibiting miR-103-3p could improve neurological outcomes of SAH rats by up-regulating Cav-1.