Donepezil attenuates injury following ischaemic stroke by stimulation of neurogenesis, angiogenesis, and inhibition of inflammation and apoptosis.
Angiogenesis Inducing Agents
/ administration & dosage
Animals
Apoptosis
/ drug effects
Donepezil
/ administration & dosage
Dose-Response Relationship, Drug
Infarction, Middle Cerebral Artery
Inflammation
/ drug therapy
Ischemic Stroke
/ drug therapy
Male
Mitochondria
/ drug effects
Neurogenesis
/ drug effects
Neuroprotective Agents
/ administration & dosage
Rats
Rats, Wistar
Angiogenesis
Apoptosis
BDNF protein
Donepezil
Focal cerebral ischaemia
Mitochondrial function
Journal
Inflammopharmacology
ISSN: 1568-5608
Titre abrégé: Inflammopharmacology
Pays: Switzerland
ID NLM: 9112626
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
13
01
2020
accepted:
05
10
2020
pubmed:
18
11
2020
medline:
21
10
2021
entrez:
17
11
2020
Statut:
ppublish
Résumé
Donepezil has proven to be an effective drug to reduce neuronal death and subsequently injury in neurodegenerative diseases. The current study evaluated the neuroprotective effects of donepezil in a rat model of ischaemic stroke and explored possible mechanisms which by this drug may reduce cell death. Temporary middle cerebral artery occlusion (tMCAO) was exerted for 45 min to induce ischaemic stroke. The animals were assigned into five groups: sham, control, and three groups treated with different doses of donepezil. Donepezil was intraperitoneally (IP) injected 4 h after reperfusion for 10 consecutive days. Infarct size was determined using TTC staining. The expression of proteins was evaluated using immunohistochemistry assays. Compared with the control group, infarct size was significantly reduced in tMCAO rats treated with different doses of donepezil. Moreover, our results showed significant decreased expression levels of apoptotic markers and pro-inflammatory mediators after treatment with different doses of donepezil for 10 days (P < 0.05). Likewise, significant increase of brain-derived neurotrophic factor (BDNF) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) proteins were found in tMCAO rats treated with donepezil compared with the control group (P < 0.05). Collectively, our findings show the validity of donepezil as a new therapeutic agent for attenuation of injury following ischaemic stroke through attenuation of inflammation and improvement of mitochondrial function, neurogenesis, and angiogenesis.
Identifiants
pubmed: 33201349
doi: 10.1007/s10787-020-00769-5
pii: 10.1007/s10787-020-00769-5
doi:
Substances chimiques
Angiogenesis Inducing Agents
0
Neuroprotective Agents
0
Donepezil
8SSC91326P
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
153-166Références
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