Abstract
Neurogenesis and angiogenesis are widely recognized to occur during epileptogenesis and important in brain development. Because vascular endothelial growth factor (VEGF) is a critical neurovascular target in neurological diseases, its effect on neurogenesis, microvascular remodeling and epileptogenesis in the immature brain after lithium-pilocarpine-induced status epilepticus (SE) was investigated. The dynamic changes in and the correlation between hippocampal neurogenesis and microvascular remodeling after SE and the influence of VEGF or SU5416 injection into the lateral ventricles at different stages after SE on neurogenesis and microvascular remodeling through regulation of VEGF expression were assessed by immunofluorescence and immunohistochemistry. Western blot analysis revealed that the VEGFR2 signaling pathway promotes phosphorylated ERK and phosphorylated AKT expression. The effects of VEGF expression regulation at different stages after SE on pathological changes in hippocampal structure and spontaneous recurrent seizures (SRS) were evaluated by Nissl staining and electroencephalography (EEG). The results showed that hippocampal neurogenesis after SE is related to microvascular regeneration. VEGF promotion in the acute period and inhibition in the latent period after SE alleviates loss of hippocampal neuron, abnormal vascular regeneration and inhibits neural stem cells (NSCs) ectopic migration, which may effectively alleviate SRS severity. Interfering with VEGF via the AKT and ERK pathways in different phases after SE may be a promising strategy for treating and preventing epilepsy in children.
Highlights
Convulsive disorders are the most common emergency in pediatric neurology
Based on observation by the naked eye, the behavioral manifestations, which mainly included spontaneous eye gaze and facial muscle twitching and rarely included unilateral or bilateral forelimb clonus, were significantly less severe in the SU5416 intervention (SU5) group than in the status epilepticus (SE) group. These results suggest that regulation of vascular endothelial growth factor (VEGF) expression in the latent phase after SE has a greater impact on the degree of epilepsy
Pathological changes in the brain occur in acute, latent phase and chronic phases after convulsive brain injury [3]
Summary
Convulsive disorders are the most common emergency in pediatric neurology. The incidence of convulsions is higher in children than in adults [1], and children are more prone to severe convulsions and status epilepticus (SE), which is associated with more serious longterm nervous system sequelae such as epilepsy, cognitive impairment, and emotional disorders and greatly affects the quality of life of children [2,3,4]. VEGF Modulates Neurogenesis and Microvascular Regeneration mechanism of epileptogenesis after SE is not fully understood, and there is no effective method for repairing convulsioninduced brain damage or effectively preventing epilepsy. The progression from acute convulsive brain injury to epileptogenesis can be divided into the acute phase, latent phase and chronic phase according to the different physiological and pathological changes that occur in the brain and the occurrence of SRS. Studies have found that a series of molecular pathological changes occur in the brain during the latent phase [5] and that SE-induced brain damage in the immature brain is different from that in the mature brain. It may be possible to prevent epileptogenesis by identifying important targets related to the mechanism of epilepsy in the immature brain
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