title: Folic acid stimulates proliferation of transplanted neural stem cells after focal cerebral ischemia in rats.
abstract: Folic acid (FA) stimulates neural stem cell (NSC) proliferation in vitro and enhances hippocampal neurogenesis in rats after middle cerebral artery occlusion (MCAO). The effect of FA supplementation on exogenous NSCs transplanted in MCAO rats was observed to determine if FA can stimulate NSC replacement after focal cerebral ischemia. Rats were randomly assigned to 3 groups: MCAO; MCAO and exogenous NSC transplantation (MCAO+NSCs); and MCAO, NSC transplantation and FA (MCAO+NSCs+FA). FA (0.8 mg/kg) or vehicle was administered by gavage daily for 28 days before MCAO and 23 days afterward. NSCs were labeled with superparamagnetic iron oxide (SPIO) and bromodeoxyuridine (BrdU) prior to transplantation into the striatum, contralateral to the ischemic zone, at 2 days post-MCAO. Magnetic resonance imaging tracking and fluorescent immunohistochemistry, as well as measurement of serum folate concentration, were performed at intervals up to 21 days after transplantation. FA supplementation caused sustained increases of 400-600% in serum folate concentration. Magnetic resonance images indicated that SPIO-labeled NSCs were more abundant at the transplantation and ischemic brain sites in MCAO+NSCs+FA rats than in MCAO+NSCs rats. Similarly, immunohistochemistry showed that the numbers of Sox-2/BrdU double positive cells at the transplantation and ischemic sites were higher in the rats that received FA. In conclusion, after focal cerebral ischemia, FA supplementation stimulates transplanted NSCs to proliferate and migrate to ischemic sites.
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.forename: Jiasong
authors.initials: J
authors.lastname: Cao
authors.forename: Haihong
authors.initials: H
authors.lastname: Zhang
authors.forename: Shanchun
authors.initials: S
authors.lastname: Qin
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.forename: Xumei
authors.initials: X
authors.lastname: Zhang
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Gao
authors.forename: John X
authors.initials: JX
authors.lastname: Wilson
authors.forename: Guowei
authors.initials: G
authors.lastname: Huang
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D002465:Cell Movement; D049109:Cell Proliferation; D003911:Dextrans; D005492:Folic Acid / Q000097:blood / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D008297:Male; D058953:Neural Stem Cells / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods
chemical_list: D003911:Dextrans; D058185:Magnetite Nanoparticles; D005492:Folic Acid; C065507:ferumoxides
keywords: Folic acid; MCAO; Neural stem cells; Proliferation; Transplantation