Fig. 7

Schematic diagram depicting the proposed mechanism involved HI-induced seizure. The evolution of seizures after HI progresses along the following steps: (1) NKCC1 expression is enhanced in RBMECs under HI, which appears to affect cytoskeletal alterations. Actin polymerization is enhanced and F-actin⁺ stress fibers are formed inside injured RBMECs. (2) Stress fiber formation causes endothelial contraction and TJs (for example, ZO-1). (3) The disassembly and redistribution of TJs lead to subtle BBB hyperpermeability and induce the recruitment of neutrophils into ischemic regions, at least in part through increased production of neutrophil chemoattractant. (4) Aberrant increase in neutrophil infiltration causes abnormal inflammation and subsequent pathological events in the brain. (5) As a result, peripheral leukocyte infiltration leads to exacerbation of inflammation and neuronal injury, which results in epilepsy and eventually seizures. By targeting the early NKCC1 upregulation, vitexin attenuates BBB disruption at the start, as well as subsequent tissue injury, thereby offering long-term functional improvements