@article{ref1,
title="Dual effects of carbon monoxide on pericytes and neurogenesis in traumatic brain injury",
journal="Nature medicine",
year="2016",
author="Choi, Yoon Kyung and Maki, Takakuni and Mandeville, Emiri T. and Koh, Seong-Ho and Hayakawa, Kazuhide and Arai, Ken and Kim, Young-Myeong and Whalen, Michael J. and Xing, Changhong and Wang, Xiaoying and Kim, Kyu-Won and Lo, Eng H.",
volume="22",
number="11",
pages="1335-1341",
abstract="At low levels, carbon monoxide (CO) has physiological roles as a second messenger and neuromodulator. 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.<p /> <p>Language: en</p>",
language="en",
issn="1078-8956",
doi="10.1038/nm.4188",
url="http://dx.doi.org/10.1038/nm.4188"
}