Journal
JOURNAL OF PHARMACY AND PHARMACOLOGY
Volume 73, Issue 5, Pages 626-640Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jpp/rgab011
Keywords
epilepsy; vinpocetine; lithium-pilocarpine; mTOR
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The study investigated the modulatory effects of Vinpocetine (VNP) on neurobehavioral comorbidities via the mTOR signaling pathway in a lithium-pilocarpine (Li-Pil) rat model of seizures. VNP demonstrated a protective effect against Li-Pil-induced seizures and improved locomotor and cognitive abilities, while also exerting a neuroprotective action through inhibitory effects on hippocampal glutamate excitotoxicity, mTOR pathway, and inflammatory and apoptotic parameters.
Objectives As one of the most frequent worldwide neurological disorders, epilepsy is an alteration of the central nervous system (CNS) characterized by abnormal increases in neuronal electrical activity. The mammalian target of rapamycin (mTOR) signalling pathway has been investigated as an interesting objective in epilepsy research. Vinpocetine (VNP), a synthesized derivative of the apovincamine alkaloid, has been used in different cerebrovascular disorders. This study aimed to examine the modulatory effects of VNP on neurobehavioral comorbidities via the mTOR signalling pathway in a lithium-pilocarpine (Li-Pil) rat model of seizures. Methods In male Wistar rats, seizures were induced with a single administration of pilocarpine (60 mg/kg; i.p.) 20 hours after the delivery of a single dose of lithium (3 mEq/kg; i.p.). VNP (10 mg/kg; i.p.) was administered daily for 14 consecutive days before Li-Pil administration. Key findings VNP had a protective effect against Li-Pil-induced seizures. VNP improved both the locomotor and cognitive abilities, moreover, VNP exerted a neuroprotective action, as verified histologically and by its inhibitory effects on hippocampal glutamate excitotoxicity, mTOR pathway, and inflammatory and apoptotic parameters. Conclusions VNP is a valuable candidate for epilepsy therapy via its modulation of the mechanisms underlying epileptogenesis with emphasis on its modulatory effect on mTOR signalling pathway.
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