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

- Status epilepticus (SE) is a common acute disorder in pediatric neurology. Vascular endothelial growth factor (VEGF) is up-regulated after SE and alleviates seizure-induced neurodegeneration. However, little is known about the mechannisim of VEGF action.
- In this study, we focus on immature brain and follow-up VEGF dynamic expression after SE From the perspective of neurogenesis in the acute phase after SE and on long-term cognitive behaviors following SE to study the role of VEGF function.
- In this study, we studied the suitable time and dose for exogenous VEGF after SE to provide future direction to unravel the downstream VEGF signaling pathways that selectively regulate vessel permeability and neuroprotection to develop future gene therapy strategies.

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.