Neuroprotective Effects of Vinpocetine and its Major Metabolite Cis‐apovincaminic Acid on NMDA‐Induced Neurotoxicity in a Rat Entorhinal Cortex Lesion Model
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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.
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EC-lesioned rats have been reported to show deficits in the NOP test with a 2-hour interval.
“The EC-lesioned rats have also been reported to show deficits in the NOP test with an 2-hour interval (Nyakas et al., 2009).”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Nyakas et al., 2009
EC-lesioned animals showed deficient spatial navigation in the Morris water maze, but not when spatial cues were provided by proximal objects located in the pool.
“EC-lesioned animals showed deficient spatial navigation in the Morris water maze (Nyakas et al., 2009; Parron et al., 2004), but not when spatial cues were provided by proximal objects located in the pool (Parron et al., 2004).”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Nyakas et al., 2009
The whole EC is likely to engage in long-term object memory, given that EC-lesioned or inactivated animals exhibited deficits in the NOP test when tested 24 hours later.
“The whole EC is likely to engage in long-term object memory, given that EC-lesioned or inactivated animals exhibited deficits in the NOP test when tested 24 hours later (Lima et al., 2009; Nyakas et al., 2009).”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Nyakas et al., 2009
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- Authors
- Nyakas, C., Felszeghy, K., Szabó, R., Keijser, J. N., Luiten, P. G. M., Szombathelyi, Z., & Tihanyi, K.
- Affiliations
- Semmelweis University (HU)
- University of Groningen (NL)
- Gedeon Richter (Hungary) (HU)
- Corresponding author
- Nyakas, Csaba
- ORCID
- Nyakas, Csaba
- Venue
- CNS Neuroscience & Therapeutics
- Publisher
- Wiley
- Published
- 2009-05-06
- Volume
- 15
- Issue
- 2
- Pages
- 89-99
- ISSN
- 1755-5930 (ISSN-L)
- 1755-5949
- PMC
- PMC6494022
- OpenAlex
- W2054843695
- Cited by
- 46
- References
- 49
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 5 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 4 · 2016: 4 · 2015: 4 · 2014: 1 · 2013: 4 · 2012: 1
- FWCI
- 1.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- CNS Neuroscience & Therapeutics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Gedeon Richter
- Hungarian Scientific Research Fund
- Topics
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- vinpocetine, NMDA neurotoxicity, entorhinal cortex lesion, neuroprotection, dementia model, microglial activation, spatial learning impairment, novel object recognition, social discrimination, spontaneous alternation, vinca alkaloids, CD11b
- MeSH terms
- Animals, Disease Models, Animal, Male, Vinca Alkaloids, N-Methylaspartate, Rats, Wistar, Neuroprotective Agents, Entorhinal Cortex, Maze Learning, Rats
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