Dual effects of carbon monoxide on pericytes and neurogenesis in traumatic brain injury
- Authors
- Choi, Yoon Kyung; Maki, Takakuni; Mandeville, Emiri T.; Koh, Seong-Ho; Hayakawa, Kazuhide; Arai, Ken; Kim, Young-Myeong; Whalen, Michael J.; Xing, Changhong; Wang, Xiaoying; Kim, Kyu-Won; Lo, Eng H.
- Issue Date
- Nov-2016
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- NATURE MEDICINE, v.22, no.11, pp.1335 - 1341
- Indexed
- SCIE
SCOPUS
- Journal Title
- NATURE MEDICINE
- Volume
- 22
- Number
- 11
- Start Page
- 1335
- End Page
- 1341
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/153661
- DOI
- 10.1038/nm.4188
- ISSN
- 1078-8956
- 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.
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