VEGF-A ameliorates ischemia hippocampal neural injury via regulating autophagy and Akt/CREB signaling in a rat model of chronic cerebral hypoperfusion.

Autor: Kang K; School of Public Health, Fudan University, Shanghai 200032, China; Department of Research and Surveillance Evaluation, Shanghai Municipal Center for Health Promotion, Shanghai 200040, China., Wang DP; Department of Neurosurgery, Tong Ji Hospital, Tong Ji University School of Medicine, Shanghai, China., Lv QL; Jiangxi Key Laboratory of Translational Cancer Research, Jiangxi Cancer Hospital, Jiangxi 330029, China. Electronic address: lvqiaoli2008@126.com., Chen F; Department of Neurosurgery, Tong Ji Hospital, Tong Ji University School of Medicine, Shanghai, China.
Jazyk: angličtina
Zdroj: Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association [J Stroke Cerebrovasc Dis] 2023 Nov; Vol. 32 (11), pp. 107367. Date of Electronic Publication: 2023 Sep 19.
DOI: 10.1016/j.jstrokecerebrovasdis.2023.107367
Abstrakt: Objective: Chronic cerebral hypoperfusion (CCH) can cause a series of pathophysiological processes, including neuronal autophagy and apoptosis. VEGF-A has been reported to affect angiogenesis and neurogenesis in many CNS diseases. However, its effects on neuronal autophagy and apoptosis, as well as the underlying mechanisms in CCH remain unclear.
Methods: To address these issues, the CCH model was established by permanent bilateral common carotid artery occlusion (2VO). Rats were sacrificed at different stages of CCH. Hippocampal morphological and ultrastructural changes were detected using HE staining and electron microscopy. The immunoreactivities of microtubule-associated protein 1 light chain 3 (LC3) and phospho-cAMP response element binding protein (p-CREB) were examined by immunofluorescence staining. The neuronal apoptosis was detected via TUNEL staining. The levels of LC3-II, Beclin-1, Akt, p-Akt, CREB, p-CREB, Caspase-3, and Bad were accessed by Western blotting. Furthermore, mouse hippocampal HT22 neurons received the oxygen and glucose deprivation (OGD) treatment, VEGF-A treatment, and GSK690693 (an Akt inhibitor) treatment, respectively.
Results: LC3-II protein started to increase at 3 days of CCH, peaked at 4 weeks of CCH, then decreased. CCH increased the levels of LC3-II, Caspase-3, and Bad, and decreased the levels of p-Akt, CREB, and p-CREB, which were reversed by VEGF-A treatment. VEGF-A also improved CCH-induced neuronal ultrastructural injuries and apoptosis in the hippocampus in vitro. In HT22, the anti-apoptosis and pro-phosphorylation of VEGF-A were reversed by GSK690693.
Conclusion: Present results provide a novel neuroprotective effect of VEGF-A in CCH that is related to the inhibition of neuronal autophagy and activation of the Akt/CREB signaling, suggesting a potential therapeutic strategy for ischemic brain damage.
Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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