VEGF Modulates Neurogenesis and Microvascular Remodeling in Epileptogenesis After Status Epilepticus in Immature Rats

Overview

Journal Front Neurol

Specialty Neurology

Date 2022 Jan 10

PMID 35002944

Authors

Wei Han

Li Jiang

Xiaojie Song

Tianyi Li

Hengsheng Chen

Li Cheng

Affiliations

Soon will be listed here.

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.

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References

Dzietko M, Derugin N, Wendland M, Vexler Z, Ferriero D . Delayed VEGF treatment enhances angiogenesis and recovery after neonatal focal rodent stroke. Transl Stroke Res. 2013; 4(2):189-200. PMC: 3733573. DOI: 10.1007/s12975-012-0221-6. View

Nicoletti J, Shah S, McCloskey D, Goodman J, Elkady A, Atassi H . Vascular endothelial growth factor is up-regulated after status epilepticus and protects against seizure-induced neuronal loss in hippocampus. Neuroscience. 2007; 151(1):232-41. PMC: 2212620. DOI: 10.1016/j.neuroscience.2007.09.083. View

Siebzehnrubl F, Blumcke I . Neurogenesis in the human hippocampus and its relevance to temporal lobe epilepsies. Epilepsia. 2008; 49 Suppl 5:55-65. DOI: 10.1111/j.1528-1167.2008.01638.x. View

Zhai X, Liang P, Li Y, Li L, Zhou Y, Wu X . Astrocytes Regulate Angiogenesis Through the Jagged1-Mediated Notch1 Pathway After Status Epilepticus. Mol Neurobiol. 2015; 53(9):5893-5901. DOI: 10.1007/s12035-015-9492-8. View

Elfving B, Wegener G . Electroconvulsive seizures stimulate the vegf pathway via mTORC1. Synapse. 2011; 66(4):340-5. DOI: 10.1002/syn.21518. View

Choi Y, Cho H, Hoyt K, Naegele J, Obrietan K . IGF-1 receptor-mediated ERK/MAPK signaling couples status epilepticus to progenitor cell proliferation in the subgranular layer of the dentate gyrus. Glia. 2008; 56(7):791-800. PMC: 4152854. DOI: 10.1002/glia.20653. View

Hellsten J, West M, Arvidsson A, Ekstrand J, Jansson L, Wennstrom M . Electroconvulsive seizures induce angiogenesis in adult rat hippocampus. Biol Psychiatry. 2005; 58(11):871-8. DOI: 10.1016/j.biopsych.2005.05.023. View

Song X, Han W, He R, Li T, Xie L, Cheng L . Alterations of Hippocampal Myelin Sheath and Axon Sprouting by Status Convulsion and Regulating Lingo-1 Expression with RNA Interference in Immature and Adult Rats. Neurochem Res. 2018; 43(3):721-735. DOI: 10.1007/s11064-018-2474-2. View

Ferrara N, Henzel W . Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. 1989. Biochem Biophys Res Commun. 2012; 425(3):540-7. DOI: 10.1016/j.bbrc.2012.08.021. View

10.

Taupin P . Adult neural stem cells, neurogenic niches, and cellular therapy. Stem Cell Rev. 2007; 2(3):213-9. DOI: 10.1007/s12015-006-0049-0. View

11.

Han W, Song X, He R, Li T, Cheng L, Xie L . VEGF regulates hippocampal neurogenesis and reverses cognitive deficits in immature rats after status epilepticus through the VEGF R2 signaling pathway. Epilepsy Behav. 2017; 68:159-167. DOI: 10.1016/j.yebeh.2016.12.007. View

12.

Fournier N, Lee B, Banasr M, Elsayed M, Duman R . Vascular endothelial growth factor regulates adult hippocampal cell proliferation through MEK/ERK- and PI3K/Akt-dependent signaling. Neuropharmacology. 2012; 63(4):642-52. PMC: 3392414. DOI: 10.1016/j.neuropharm.2012.04.033. View

13.

Haut S, Veliskova J, Moshe S . Susceptibility of immature and adult brains to seizure effects. Lancet Neurol. 2004; 3(10):608-17. DOI: 10.1016/S1474-4422(04)00881-6. View

14.

Kilic E, Kilic U, Wang Y, Bassetti C, Marti H, Hermann D . The phosphatidylinositol-3 kinase/Akt pathway mediates VEGF's neuroprotective activity and induces blood brain barrier permeability after focal cerebral ischemia. FASEB J. 2006; 20(8):1185-7. DOI: 10.1096/fj.05-4829fje. View

15.

Ogaki A, Ikegaya Y, Koyama R . Vascular Abnormalities and the Role of Vascular Endothelial Growth Factor in the Epileptic Brain. Front Pharmacol. 2020; 11:20. PMC: 7010950. DOI: 10.3389/fphar.2020.00020. View

16.

Ben-Ari Y, Holmes G . Effects of seizures on developmental processes in the immature brain. Lancet Neurol. 2006; 5(12):1055-63. DOI: 10.1016/S1474-4422(06)70626-3. View

17.

Pierce J, Punsoni M, McCloskey D, Scharfman H . Mossy cell axon synaptic contacts on ectopic granule cells that are born following pilocarpine-induced seizures. Neurosci Lett. 2007; 422(2):136-40. PMC: 3119631. DOI: 10.1016/j.neulet.2007.06.016. View

18.

Tavazoie M, van der Veken L, Silva-Vargas V, Louissaint M, Colonna L, Zaidi B . A specialized vascular niche for adult neural stem cells. Cell Stem Cell. 2008; 3(3):279-88. PMC: 6864413. DOI: 10.1016/j.stem.2008.07.025. View

19.

Jung K, Chu K, Lee S, Kim J, Sinn D, Kim J . Cyclooxygenase-2 inhibitor, celecoxib, inhibits the altered hippocampal neurogenesis with attenuation of spontaneous recurrent seizures following pilocarpine-induced status epilepticus. Neurobiol Dis. 2006; 23(2):237-46. DOI: 10.1016/j.nbd.2006.02.016. View

20.

Benini R, Roth R, Khoja Z, Avoli M, Wintermark P . Does angiogenesis play a role in the establishment of mesial temporal lobe epilepsy?. Int J Dev Neurosci. 2016; 49:31-6. PMC: 4878886. DOI: 10.1016/j.ijdevneu.2016.01.001. View