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Secondary hypoxic ischemia alters neurobehavioral outcomes, neuroinflammation, and oxidative stress in mice exposed to controlled cortical impact

OBJECTIVE: Hypoxic ischemia (HI) is a secondary insult that can cause fatal neurologic outcomes after traumatic brain injury (TBI), ranging from mild cognitive deficits to persistent vegetative states. We here aimed to unravel the underlying pathological mechanisms of HI injury in a TBI mouse model....

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Autores principales: Oh, Se-Kwang, Park, Hyun-Jeong, Yu, Gyeong-Gyu, Jeong, Seong-Hae, Lee, Suk-Woo, Kim, Hoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society of Emergency Medicine 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517469/
https://www.ncbi.nlm.nih.gov/pubmed/34649410
http://dx.doi.org/10.15441/ceem.20.124
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author Oh, Se-Kwang
Park, Hyun-Jeong
Yu, Gyeong-Gyu
Jeong, Seong-Hae
Lee, Suk-Woo
Kim, Hoon
author_facet Oh, Se-Kwang
Park, Hyun-Jeong
Yu, Gyeong-Gyu
Jeong, Seong-Hae
Lee, Suk-Woo
Kim, Hoon
author_sort Oh, Se-Kwang
collection PubMed
description OBJECTIVE: Hypoxic ischemia (HI) is a secondary insult that can cause fatal neurologic outcomes after traumatic brain injury (TBI), ranging from mild cognitive deficits to persistent vegetative states. We here aimed to unravel the underlying pathological mechanisms of HI injury in a TBI mouse model. METHODS: Neurobehavior, neuroinflammation, and oxidative stress were assessed in a mouse model of controlled cortical impact (CCI) injury followed by HI. Mice underwent CCI alone, CCI followed by HI, HI alone, or sham operation. HI was induced by one-vessel carotid ligation with 1 hour of 8% oxygen in nitrogen. Learning and memory were assessed using the novel object recognition test, contextual and cued fear conditioning, and Barnes maze test. Brain cytokine production and oxidative stress-related components were measured. RESULTS: Compared to TBI-only animals, TBI followed by HI mice exhibited significantly poorer survival and health scores, spatial learning and memory in the Barnes maze test, discrimination memory in the novel object recognition test, and fear memory following contextual and cued fear conditioning. Malondialdehyde levels were significantly lower, whereas glutathione peroxidase activity was significantly higher in TBI followed by HI mice compared to TBI-only and sham counterparts, respectively. Interleukin-6 levels were significantly higher in TBI followed by HI mice compared to both TBI-only and sham animals. CONCLUSION: Post-traumatic HI aggravated deficits in spatial, fear, and discrimination memory in an experimental TBI mouse model. Our results suggest that increased neuroinflammation and oxidative stress contribute to HI-induced neurobehavioral impairments after TBI.
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spelling pubmed-85174692021-10-26 Secondary hypoxic ischemia alters neurobehavioral outcomes, neuroinflammation, and oxidative stress in mice exposed to controlled cortical impact Oh, Se-Kwang Park, Hyun-Jeong Yu, Gyeong-Gyu Jeong, Seong-Hae Lee, Suk-Woo Kim, Hoon Clin Exp Emerg Med Original Article OBJECTIVE: Hypoxic ischemia (HI) is a secondary insult that can cause fatal neurologic outcomes after traumatic brain injury (TBI), ranging from mild cognitive deficits to persistent vegetative states. We here aimed to unravel the underlying pathological mechanisms of HI injury in a TBI mouse model. METHODS: Neurobehavior, neuroinflammation, and oxidative stress were assessed in a mouse model of controlled cortical impact (CCI) injury followed by HI. Mice underwent CCI alone, CCI followed by HI, HI alone, or sham operation. HI was induced by one-vessel carotid ligation with 1 hour of 8% oxygen in nitrogen. Learning and memory were assessed using the novel object recognition test, contextual and cued fear conditioning, and Barnes maze test. Brain cytokine production and oxidative stress-related components were measured. RESULTS: Compared to TBI-only animals, TBI followed by HI mice exhibited significantly poorer survival and health scores, spatial learning and memory in the Barnes maze test, discrimination memory in the novel object recognition test, and fear memory following contextual and cued fear conditioning. Malondialdehyde levels were significantly lower, whereas glutathione peroxidase activity was significantly higher in TBI followed by HI mice compared to TBI-only and sham counterparts, respectively. Interleukin-6 levels were significantly higher in TBI followed by HI mice compared to both TBI-only and sham animals. CONCLUSION: Post-traumatic HI aggravated deficits in spatial, fear, and discrimination memory in an experimental TBI mouse model. Our results suggest that increased neuroinflammation and oxidative stress contribute to HI-induced neurobehavioral impairments after TBI. The Korean Society of Emergency Medicine 2021-09-30 /pmc/articles/PMC8517469/ /pubmed/34649410 http://dx.doi.org/10.15441/ceem.20.124 Text en Copyright © 2021 The Korean Society of Emergency Medicine https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ).
spellingShingle Original Article
Oh, Se-Kwang
Park, Hyun-Jeong
Yu, Gyeong-Gyu
Jeong, Seong-Hae
Lee, Suk-Woo
Kim, Hoon
Secondary hypoxic ischemia alters neurobehavioral outcomes, neuroinflammation, and oxidative stress in mice exposed to controlled cortical impact
title Secondary hypoxic ischemia alters neurobehavioral outcomes, neuroinflammation, and oxidative stress in mice exposed to controlled cortical impact
title_full Secondary hypoxic ischemia alters neurobehavioral outcomes, neuroinflammation, and oxidative stress in mice exposed to controlled cortical impact
title_fullStr Secondary hypoxic ischemia alters neurobehavioral outcomes, neuroinflammation, and oxidative stress in mice exposed to controlled cortical impact
title_full_unstemmed Secondary hypoxic ischemia alters neurobehavioral outcomes, neuroinflammation, and oxidative stress in mice exposed to controlled cortical impact
title_short Secondary hypoxic ischemia alters neurobehavioral outcomes, neuroinflammation, and oxidative stress in mice exposed to controlled cortical impact
title_sort secondary hypoxic ischemia alters neurobehavioral outcomes, neuroinflammation, and oxidative stress in mice exposed to controlled cortical impact
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517469/
https://www.ncbi.nlm.nih.gov/pubmed/34649410
http://dx.doi.org/10.15441/ceem.20.124
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