vitamin-b-12 and Infarction--Middle-Cerebral-Artery

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.

Topics: Animals; Apoptosis; Autophagy; Brain Ischemia; Cell Line; Cell Survival; Cytokines; Disease Models, Animal; Infarction, Middle Cerebral Artery; Male; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Neuroprotective Agents; Protein Kinase Inhibitors; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Vitamin B 12

To investigate the effects of folic acid, vitamin B(6) and B(12) on plasma homocysteine and on learning and memory functions in focal cerebral ischemia rats.. Sprague-Dawley rats were randomly divided into four groups. They were sham operation group (Sham OP), middle cerebral artery occlusion model group (MCAO), MCAO + folic acid group (MCAO + FA) and MCAO + compound vitamin (folate, vitamin B(6) and B(12)) group (MCAO + CV). Plasma homocysteine was measured before and after supplementation and after ischemia.. The level of plasma homocysteine in MCAO + FA and MCAO + CV groups were significantly lower than those in Sham OP and MCAO groups after supplementation and ischemia (6.92 +/- 1.04) micromol/L and (5.49 +/- 1.00) micromol/L vs (9.33 +/- 1.11) micromol/L, (10.90 +/- 2.03 micromol/L), P < 0.05. While in MCAO + CV group was lower than that in MCAO + FA group (5.49 +/- 1.00) micromol/L vs (6.92 +/- 1.04) micromol/L, P < 0.05. The neurological deficit scores and shock times in Y-type maze of MCAO + FA and MCAO + CV groups were lower than those in MCAO group (1.75 +/- 0.46 and 1.38 +/- 0.52 vs 2.62 +/- 0.52; 123.50 +/- 39.77 and 86.25 +/- 21.39 vs 173.25 +/- 46.32, P < 0.05). The correct times of MCAO + CV group in Y-type maze was higher than that in MCAO group (3.75 +/- 0.42 vs 2.12 +/- 0.45, P < 0.05).. Folic acid intake could not only reduce plasma homocysteine concentration but also promote the recovery of the learning and memory functions of rats with cerebral ischemia. The effects of folic acid combined with vitamin B(6) and vitamin B(12) on cerebral ischemia rats was better than that of single folate.

Topics: Animals; Brain Ischemia; Disease Models, Animal; Female; Folic Acid; Homocysteine; Infarction, Middle Cerebral Artery; Learning; Male; Memory; Rats; Rats, Sprague-Dawley; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Topics: 5,10-Methylenetetrahydrofolate Reductase (FADH2); Abortion, Habitual; Brain; Female; Folic Acid; Genetic Predisposition to Disease; Homocysteine; Humans; Hyperhomocysteinemia; Infarction, Middle Cerebral Artery; Middle Aged; Mutation; Platelet Aggregation Inhibitors; Pregnancy; Stroke; Treatment Outcome; Vitamin B 12