title: VEGF regulates hippocampal neurogenesis and reverses cognitive deficits in immature rats after status epilepticus through the VEGF R2 signaling pathway.
abstract: 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.
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Song
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China.
authors.forename: Rong
authors.initials: R
authors.lastname: He
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Li
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China.
authors.forename: Li
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Neurology, Children's Hospital of Chongqing Medical University, 136 Zhongshan 2nd Road, Chongqing 400014, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Xie
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China.
authors.forename: Hengsheng
authors.initials: H
authors.lastname: Chen
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China; Department of Neurology, Children's Hospital of Chongqing Medical University, 136 Zhongshan 2nd Road, Chongqing 400014, China. Electronic address: dr_jiangli@hotmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D055495:Neurogenesis / Q000187:drug effects*; D010862:Pilocarpine; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D042461:Vascular Endothelial Growth Factor A; D010862:Pilocarpine
keywords: Cognitive deficits; Neurogenesis; Status epilepticus; VEGF