Human neural stem cell transplantation attenuates apoptosis and improves neurological functions after cerebral ischemia in rats.
BACKGROUND
Neuroprotection is a major therapeutic approach for ischemic brain injury. We investigated the neuroprotective effects induced by transplantation of human embryonic neural stem cells (NSCs) into the cortical penumbra 24 h after focal cerebral ischemia.


METHODS
NSCs were prepared from human embryonic brains obtained at 8 weeks of gestation. Focal cerebral ischemia was induced in adult rats by permanent occlusion of the middle cerebral artery. Animals were randomly divided into two groups: NSCs-grafted group and medium-grafted group (control). Infarct size was assessed 28 days after transplantation by hematoxylin and eosin staining. Neurological severity scores were evaluated before ischemia and at 1, 7, 14, and 28 days after transplantation. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and immunohistochemical analysis of Bcl-2 and Bax were performed at 7, 14, and 28 days after transplantation.


RESULTS
Physiological parameters of the two groups were comparable, but not significantly different. NSC transplantation significantly improved neurological function (P<0.05) but did not reduce the infarct size significantly (P>0.05). Compared with the control, NSC transplantation significantly reduced the number of TUNEL- and Bax-positive cells in the penumbra at 7 days. Interestingly, the number of Bcl-2-positive cells in the penumbra after NSC transplantation was significantly higher than that after medium transplantation (P<0.05).


CONCLUSIONS
The results indicate that NSC transplantation has anti-apoptotic activity and can improve the neurological function; these effects are mediated by the up-regulation of Bcl-2 expression in the penumbra.
Zhang
P
P
Institute of Neurobiology, National Key Academic Subject of Physiology, Xi'an Jiaotong University School of Medicine, Xi'an, China.
Li
J
J
Liu
Y
Y
Chen
X
X
Kang
Q
Q
Zhao
J
J
Li
W
W
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D002540:Cerebral Cortex / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D002544:Cerebral Infarction / Q000473:pathology; D053938:DNA Fragmentation; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D009420:Nervous System / Q000503:physiopathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics
D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein