VEGF regulates hippocampal neurogenesis and reverses cognitive deficits in immature rats after status epilepticus through the VEGF R2 signaling pathway.

Epilepsy is the most common chronic disease in children, who exhibit a higher risk for status epilepticus (SE) than adults. Hippocampal neurogenesis is altered by epilepsy, particularly in the immature brain, which may influence cognitive development. Vascular endothelial growth factor (VEGF) represents an attractive target to modulate brain function at the neurovascular interface and is a double-edged sword in seizures. We used the lithium-pilocarpine-induced epilepsy model in immature Sprague-Dawley rats to study the effects of VEGF on hippocampal neurogenesis in the acute phase and on long-term cognitive behaviors in immature rats following status epilepticus (SE). VEGF correlates with cell proliferation in the immature brain after SE. By preprocessing VEGF in the lateral ventricles prior to the induction of the SE model, we found that VEGF increased the proliferation of neural stem cells (NSCs) and promoted the migration of newly generated cells via the VEGF receptor 2 (VEGFR2) signaling pathway. VEGF also inhibited cell loss and reversed the cognitive deficits that accompany SE. Based on our results, VEGF positively contributes to the initial stages of neurogenesis and alleviates cognitive deficits following seizures; moreover, the VEGF/VEGFR2 signaling pathway may provide a novel treatment strategy for epilepsy.