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Effects of Acute Systemic Hypoxia and Hypercapnia on Brain Damage in a Rat Model of Hypoxia-Ischemia
Therapeutic hypercapnia has the potential for neuroprotection after global cerebral ischemia. Here we further investigated the effects of different degrees of acute systemic hypoxia in combination with hypercapnia on brain damage in a rat model of hypoxia and ischemia. Adult wistar rats underwent un...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131999/ https://www.ncbi.nlm.nih.gov/pubmed/27907083 http://dx.doi.org/10.1371/journal.pone.0167359 |
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author | Yang, Wanchao Zhang, Xuezhong Wang, Nan Tan, Jing Fang, Xianhai Wang, Qi Tao, Tao Li, Wenzhi |
author_facet | Yang, Wanchao Zhang, Xuezhong Wang, Nan Tan, Jing Fang, Xianhai Wang, Qi Tao, Tao Li, Wenzhi |
author_sort | Yang, Wanchao |
collection | PubMed |
description | Therapeutic hypercapnia has the potential for neuroprotection after global cerebral ischemia. Here we further investigated the effects of different degrees of acute systemic hypoxia in combination with hypercapnia on brain damage in a rat model of hypoxia and ischemia. Adult wistar rats underwent unilateral common carotid artery (CCA) ligation for 60 min followed by ventilation with normoxic or systemic hypoxic gas containing 11%O(2),13%O(2),15%O(2) and 18%O(2) (targeted to PaO(2) 30–39 mmHg, 40–49 mmHg, 50–59 mmHg, and 60–69 mmHg, respectively) or systemic hypoxic gas containing 8% carbon dioxide (targeted to PaCO(2) 60–80 mmHg) for 180 min. The mean artery pressure (MAP), blood gas, and cerebral blood flow (CBF) were evaluated. The cortical vascular permeability and brain edema were examined. The ipsilateral cortex damage and the percentage of hippocampal apoptotic neurons were evaluated by Nissl staining and terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling (TUNEL) assay as well as flow cytometry, respectively. Immunofluorescence and western blotting were performed to determine aquaporin-4 (AQP4) expression. In rats treated with severe hypoxia (PaO(2) < 50 mmHg), hypercapnia augmented the decline of MAP with cortical CBF and damaged blood–brain barrier permeability (p < 0.05). In contrast, in rats treated with mild to moderate hypoxia (PaO(2) > 50 mmHg), hypercapnia protected against these pathophysiological changes. Moreover, hypercapnia treatment significantly reduced brain damage in the ischemic ipsilateral cortex and decreased the percentage of apoptotic neurons in the hippocampus after the CCA ligated rats were exposed to mild or moderate hypoxemia (PaO(2) > 50 mmHg); especially under mild hypoxemia (PaO(2) > 60 mmHg), hypercapnia significantly attenuated the expression of AQP4 protein with brain edema (p < 0.05). Hypercapnia exerts beneficial effects under mild to moderate hypoxemia and augments detrimental effects under severe hypoxemia on brain damage in a rat model of hypoxia-ischemia. |
format | Online Article Text |
id | pubmed-5131999 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-51319992016-12-21 Effects of Acute Systemic Hypoxia and Hypercapnia on Brain Damage in a Rat Model of Hypoxia-Ischemia Yang, Wanchao Zhang, Xuezhong Wang, Nan Tan, Jing Fang, Xianhai Wang, Qi Tao, Tao Li, Wenzhi PLoS One Research Article Therapeutic hypercapnia has the potential for neuroprotection after global cerebral ischemia. Here we further investigated the effects of different degrees of acute systemic hypoxia in combination with hypercapnia on brain damage in a rat model of hypoxia and ischemia. Adult wistar rats underwent unilateral common carotid artery (CCA) ligation for 60 min followed by ventilation with normoxic or systemic hypoxic gas containing 11%O(2),13%O(2),15%O(2) and 18%O(2) (targeted to PaO(2) 30–39 mmHg, 40–49 mmHg, 50–59 mmHg, and 60–69 mmHg, respectively) or systemic hypoxic gas containing 8% carbon dioxide (targeted to PaCO(2) 60–80 mmHg) for 180 min. The mean artery pressure (MAP), blood gas, and cerebral blood flow (CBF) were evaluated. The cortical vascular permeability and brain edema were examined. The ipsilateral cortex damage and the percentage of hippocampal apoptotic neurons were evaluated by Nissl staining and terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling (TUNEL) assay as well as flow cytometry, respectively. Immunofluorescence and western blotting were performed to determine aquaporin-4 (AQP4) expression. In rats treated with severe hypoxia (PaO(2) < 50 mmHg), hypercapnia augmented the decline of MAP with cortical CBF and damaged blood–brain barrier permeability (p < 0.05). In contrast, in rats treated with mild to moderate hypoxia (PaO(2) > 50 mmHg), hypercapnia protected against these pathophysiological changes. Moreover, hypercapnia treatment significantly reduced brain damage in the ischemic ipsilateral cortex and decreased the percentage of apoptotic neurons in the hippocampus after the CCA ligated rats were exposed to mild or moderate hypoxemia (PaO(2) > 50 mmHg); especially under mild hypoxemia (PaO(2) > 60 mmHg), hypercapnia significantly attenuated the expression of AQP4 protein with brain edema (p < 0.05). Hypercapnia exerts beneficial effects under mild to moderate hypoxemia and augments detrimental effects under severe hypoxemia on brain damage in a rat model of hypoxia-ischemia. Public Library of Science 2016-12-01 /pmc/articles/PMC5131999/ /pubmed/27907083 http://dx.doi.org/10.1371/journal.pone.0167359 Text en © 2016 Yang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Yang, Wanchao Zhang, Xuezhong Wang, Nan Tan, Jing Fang, Xianhai Wang, Qi Tao, Tao Li, Wenzhi Effects of Acute Systemic Hypoxia and Hypercapnia on Brain Damage in a Rat Model of Hypoxia-Ischemia |
title | Effects of Acute Systemic Hypoxia and Hypercapnia on Brain Damage in a Rat Model of Hypoxia-Ischemia |
title_full | Effects of Acute Systemic Hypoxia and Hypercapnia on Brain Damage in a Rat Model of Hypoxia-Ischemia |
title_fullStr | Effects of Acute Systemic Hypoxia and Hypercapnia on Brain Damage in a Rat Model of Hypoxia-Ischemia |
title_full_unstemmed | Effects of Acute Systemic Hypoxia and Hypercapnia on Brain Damage in a Rat Model of Hypoxia-Ischemia |
title_short | Effects of Acute Systemic Hypoxia and Hypercapnia on Brain Damage in a Rat Model of Hypoxia-Ischemia |
title_sort | effects of acute systemic hypoxia and hypercapnia on brain damage in a rat model of hypoxia-ischemia |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131999/ https://www.ncbi.nlm.nih.gov/pubmed/27907083 http://dx.doi.org/10.1371/journal.pone.0167359 |
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