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Neuroprotective effects of methylcobalamin in cerebral ischemia/reperfusion injury through activation of the ERK1/2 signaling pathway
- Source :
- International Immunopharmacology. 99:108040
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Despite advances in the understanding of the pathophysiology of ischemic stroke, therapeutic options remain limited. Methylcobalamin is an endogenous vitamin B12 that exhibits anti-inflammatory and antiapoptotic activities in a variety of diseases. In this study, we aimed to explore the neuroprotective effects and mechanism of action of methylcobalamin on cerebral ischemic injury in vitro and in vivo. The oxygen and glucose deprivation/reperfusion model and middle cerebral artery occlusion model were used to simulate cerebral ischemic injury in vitro and in vivo. Cell viability, inflammatory factors, cell apoptosis, and protein expression levels were determined. Further, autophagy flux and the cerebral infarction volume were measured. The modified neurological severity score, Longa score, Rotarod assay, and foot-fault test were used to evaluate behavioral changes and neurological deficits in rats. In vitro, methylcobalamin significantly increased cell viability, decreased lactate dehydrogenase release, attenuated inflammatory cytokine expression, reduced the apoptotic proportion, and enhanced autophagy flux after OGD treatment. In addition, Bcl-2 and Beclin1 expression levels and the LC3 II/I ratio were increased, whereas levels of Bax and cleaved caspase-3 were decreased. In vivo, methylcobalamin significantly reduced the cerebral infarction volume and neurological deficits in the rats. Furthermore, methylcobalamin activated the ERK1/2 pathway, whereas ERK1/2 inhibitors diminished its effects in the in vitro and in vivo models. In conclusion, methylcobalamin may exert a neuroprotective effect on cerebral ischemia and is a promising drug candidate for developing novel neuroprotective therapies.
- Subjects :
- Male
Cell Survival
MAP Kinase Signaling System
Immunology
Ischemia
Apoptosis
Pharmacology
Neuroprotection
Rotarod performance test
Brain Ischemia
Cell Line
Rats, Sprague-Dawley
In vivo
Autophagy
medicine
Animals
Immunology and Allergy
Viability assay
Protein Kinase Inhibitors
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
business.industry
Cerebral infarction
Infarction, Middle Cerebral Artery
medicine.disease
Rats
Disease Models, Animal
Vitamin B 12
Neuroprotective Agents
Reperfusion Injury
Methylcobalamin
Cytokines
business
Reperfusion injury
medicine.drug
Subjects
Details
- ISSN :
- 15675769
- Volume :
- 99
- Database :
- OpenAIRE
- Journal :
- International Immunopharmacology
- Accession number :
- edsair.doi.dedup.....82768a7837725640b79e1cd73e5a5034