Neuroprotective Effects of Vinpocetine and its Major Metabolite Cis‐apovincaminic Acid on NMDA‐Induced Neurotoxicity in a Rat Entorhinal Cortex Lesion Model

Vinpocetine (ethyl‐apovincaminate, Cavinton), a synthetic derivative of the Vinca minor alkaloid vincamine, has been used now for decades for prevention and treatment of cerebrovascular diseases predisposing to development of dementia. Both vinpocetine and its main metabolite cis‐apovincaminic acid...

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Published in:CNS neuroscience & therapeutics 2009-06, Vol.15 (2), p.89-99
Main Authors: Nyakas, Csaba, Felszeghy, Klára, Szabó, Róbert, Keijser, Jan N., Luiten, Paul G.M., Szombathelyi, Zsolt, Tihanyi, Károly
Format: Article
Language:English
Subjects:
Animals
Attention and learning
Biological and medical sciences
Dementia model
Disease Models, Animal
Drug toxicity and drugs side effects treatment
Entorhinal Cortex - drug effects
Entorhinal Cortex - metabolism
Entorhinal Cortex - pathology
Injuries of the nervous system and the skull. Diseases due to physical agents
Lesion size
Male
Maze Learning - drug effects
Maze Learning - physiology
Medical sciences
Microglia activation
N-Methylaspartate - toxicity
Neuropharmacology
Neuroprotection
Neuroprotective agent
Neuroprotective Agents - metabolism
Neuroprotective Agents - pharmacology
Pharmacology. Drug treatments
Rats
Rats, Wistar
Toxicity: nervous system and muscle
Traumas. Diseases due to physical agents
Vinca Alkaloids - metabolism
Vinca Alkaloids - pharmacology
Vinca minor
Vinpocetine
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Summary:Vinpocetine (ethyl‐apovincaminate, Cavinton), a synthetic derivative of the Vinca minor alkaloid vincamine, has been used now for decades for prevention and treatment of cerebrovascular diseases predisposing to development of dementia. Both vinpocetine and its main metabolite cis‐apovincaminic acid (cAVA) exert a neuroprotective type of action. Bilateral N‐methyl‐D‐aspartate (NMDA)‐induced neurodegeneration in the entorhinal cortex of rat was used as a dementia model to confirm the neuroprotective action of these compounds in vivo. NMDA‐lesioned rats were treated 60 min before lesion and throughout 3 postoperative days with a 10 mg/kg intraperitoneal dose of vinpocetine or cAVA. Behavioral tests started after termination of drug treatment and consisted of novel object recognition, social discrimination, and spontaneous alternation in a Y‐maze, and spatial learning in the Morris water maze. At the end of behavioral testing brains were perfused with fixative and the size of the excitotoxic neuronal lesion and that of microglial activation around the lesion were assayed quantitatively on brain sections immunostained for neuron‐specific nuclear protein (NeuN) and integrin CD11b, respectively. Entorhinal NMDA lesions impaired recognition of novel objects and the new social partner, and suppressed spontaneous alternation and spatial learning performance in the Morris maze. Both vinpocetine and cAVA effectively attenuated the behavioral deficits, and significantly decreased lesion size and the region of microglia activation. Both lesion‐induced attention deficit and learning disabilities were markedly alleviated by vinpocetine and cAVA. The morphological findings corroborated the behavioral observations and indicated reduced lesion size and microglia activation especially after vinpocetine treatment which supports an in vivo neuroprotective mode of action of vinpocitine and a less potent action of cAVA.
ISSN:1755-5930
1755-5949
DOI:10.1111/j.1755-5949.2009.00078.x