iPLA2β/p38 MAPK alleviates the blood brain barrier disruption and brain injury in rats after TBI by inhibiting autophagy and tight junction damage: In vitro and in vivo studies

Traumatic brain injury (TBI) is one of the major causes of morbidity and mortality among adults. Blood brain barrier (BBB) damage is one of the main factors of secondary injury following TBI. However, whether iPLA2β activity affected vascular endothelial cells after TBI and its mechanism remains unclear. To investigate this, Feeney's weight-drop model in rats and H 2 O 2 induced oxidative stress model in bEnd.3 cells were established, s-BEL (an inhibitor of iPLA2β) and ATP (an agonist of iPLA2β) were used for treatment. Behavioral assessments, BBB permeability, Immunofluorescence, Transmission Electron Microscopy, ROS, etc. are applied in the research. We found that TBI lead to autophagy in cerebral vascular endothelial cells of rats. s-BEL exacerbated ZO1 and Occludin damage, as well as BBB disruption through autophagy, whereas ATP protected the BBB from damage. Inhibiting autophagy reduced ZO1 and Occludin damage caused by decreased iPLA2β activity in bEnd.3. Inhibiting p38 MAPK could alleviate excessive autophagy and the damage to ZO1 and Occludin. In conclusion, the decreased iPLA2β activity following TBI in rats leads to increased autophagy in vascular endothelial cells and BBB disruption. The iPLA2β/p38 MAPK pathway could inhibit endothelial cells autophagy, alleviate tight junction damage and BBB disruption, thereby improving brain injury. • The decreased iPLA2β activity after TBI leads to increased autophagy, tight junction proteins damage and BBB disruption. • Increasing iPLA2β activity can inhibit autophagy, reduce tight junction protein damage, and improve BBB in TBI and in vitro. • The p38 MAPK pathway is involved in the inhibition of autophagy by iPLA2β and its protective effect on BBB.