Structural and functional improvement of injured brain after severe acute carbon monoxide poisoning by stem cell-based therapy in rats.
OBJECTIVE
We investigated the feasibility and efficacy of bone marrow mesenchymal stem cells (BMSCs)-derived neural stem-like cells (MS-NSCs) therapy on injured brain in rats after severe acute carbon monoxide (CO) poisoning.


METHODS
Controlled animal study.


METHODS
Research laboratory of a university hospital.


METHODS
Sprague-Dawley rats weighing 230 +/- 20 g and 90 +/- 10 g.


METHODS
The rats were exposed to 1000 ppm CO in air for 40 minutes and then to 3000 ppm for another 20 minutes until they lost consciousness. Approximately 7 x 10 allogeneic BMSCs or MS-NSCs labeled with BrdU were infused into the poisoned rats via the internal carotid after a 24-hour resuscitation. The rats with and without CO poisoning were used as placebo and sham controls, respectively.


RESULTS
The neurologic and cognitive functions were evaluated by Neurologic Severity Scores and Morris water maze tests. Examinations with immunohistochemistry, myelin, and hematoxylin-eosin staining were made to assess cerebral structure after 5 weeks. Histologically, the compactness and arrangement of the insulted white matter were improved by the cellular treatments. The transplanted MS-NSCs were positive for microtubule-associated protein 2 in hippocampus, 84.6% +/- 5.6%, and for glial fibrillary acidic protein in subventricular white matter and hippocampus, 32.2% +/- 2.5% and 9.7% +/- 1.2%, respectively, although the MS-NSCs group showed a larger fraction in the expression of the above markers in corresponding domains compared with the BMSCs group. The MS-NSCs also displayed a higher survival rate than BMSCs in most domains of diffusively injured brain, leading to a better improvement in the Morris water maze test (p < 0.05).


CONCLUSIONS
The stem cell-based therapy could be advantageous for improving the structure and function of injured brain in rats after severe acute CO poisoning, indicating the potential use as a novel approach for severely CO-poisoned patients with delayed neurologic sequelae. Furthermore, MS-NSCs may render better therapeutic effects after neurologic injury than untreated BMSCs.
Jiang
Guoping
G
Emergency Center, Zhejiang University, Hangzhou, China.
Gao
Jianping
J
Xu
Yongshan
Y
Ma
Yuefeng
Y
Jiang
Guanyu
G
Yan
Weiqi
W
D000818:Animals; D001854:Bone Marrow Cells; D001927:Brain Diseases / Q000209:etiology* / Q000601:surgery*; D002249:Carbon Monoxide Poisoning / Q000150:complications*; D005240:Feasibility Studies; D045164:Mesenchymal Stem Cell Transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index