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Dual effects of carbon monoxide on pericytes and neurogenesis in traumatic brain injury

Title
Dual effects of carbon monoxide on pericytes and neurogenesis in traumatic brain injury
Author
고성호
Keywords
ADULT BRAIN; DISEASE
Issue Date
2016-09
Publisher
NATURE PUBLISHING GROUP
Citation
NATURE MEDICINE, v. 22, NO. 11, Page. 1335-1341
Abstract
At low levels, carbon monoxide (CO) has physiological roles as a second messenger and neuromodulator(1,2). Here we assess the effects of CO in a mouse model of traumatic brain injury (TBI). Treatment with CO-releasing molecule (CORM)-3 reduced pericyte death and ameliorated the progression of neurological deficits. In contrast, although treatment with the radical scavenger N-tert-butyl-a-phenylnitrone (PBN) also reduced pericyte death, neurological outcomes were not rescued. As compared to vehicle-treated control and PBN-treated mice, CORM-3-treated mice showed higher levels of phosphorylated neural nitric oxide synthase within neural stem cells (NSCs). Inhibition of nitric oxide synthase diminished the CORM-3-mediated increase in the number of cells that stained positive for both the neuronal marker NeuN and 5-bromo-2'-deoxyuridine (BrdU; a marker for proliferating cells) in vivo, consequently interfering with neurological recovery after TBI. Because NSCs seemed to be in close proximity to pericytes, we asked whether cross-talk between pericytes and NSCs was induced by CORM-3, thereby promoting neurogenesis. In pericyte cultures that were undergoing oxygen and glucose deprivation, conditioned cell culture medium collected after CORM-3 treatment enhanced the in vitro differentiation of NSCs into mature neurons. Taken together, these findings suggest that CO treatment may provide a therapeutic approach for TBI by preventing pericyte death, rescuing cross-talk with NSCs and promoting neurogenesis.
URI
https://www.nature.com/articles/nm.4188http://repository.hanyang.ac.kr/handle/20.500.11754/76770
ISSN
1078-8956; 1546-170X
DOI
10.1038/nm.4188
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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