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.4188https://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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