Potential Mechanisms Involved in the Anticonvulsant Effect of Recombinant Human VEGF on Maximal Electroshock-induced Seizure

Vascular endothelial growth factor (VEGF) signaling pathway plays an important role in the pathogenesis of seizure. The oxidant/antioxidant factors and miRNA expression in the brain are differentially regulated in seizure.

We aim to investigate the potential mechanism of action for the recombinant human VEGF (rhVEGF) in mice with maximal electroshock (MES)-induced seizure.

A total of 40 male mice (weight: 20-25 g) were treated intraperitoneally with normal saline, or rhVEGF (50, 100, and 150 µg/kg, daily for 4 consecutive days). One hour after the last injection, seizures were induced in each animal by MES. The latency for the onset of the first clonus and the duration of hind limb extension (HLE) were recorded. The levels of nitric oxide (NO), total antioxidant capacity (TAC), and micoRNA-142-5p expression were determined in the hippocampus of mice. Blood-brain barrier (BBB) permeability was also estimated by Evans blue dye extravasation method.

The administration of rhVEGF at all doses significantly reduced the HLE duration. However, latency for the seizure onset increased after administration of 50 and 150 μg/kg rhVEGF and decreased after administration of 100 μg/kg rhVEGF. In the brain, the NO level decreased, while TAC level and microRNA-142-5p expression increased by rhVEGF treatment in mice with MES-induced seizure. Pretreatment with rhVEGF at doses of 100 and 150 μg/kg reversed the increase in BBB leakage induced by MES-induced seizures.

The rhVEGF administration can prevent MES-induced seizures by regulating NO, TAC, and miR-142-5 expression levels in the hippocampus and reducing BBB leakage in mice.