https://scholars.lib.ntu.edu.tw/handle/123456789/626897
標題: | Inhaled Carbon Dioxide Improves Neurological Outcomes by Downregulating Hippocampal Autophagy and Apoptosis in an Asphyxia-Induced Cardiac Arrest and Resuscitation Rat Model | 作者: | CHIH-HUNG WANG CHIEN-HUA HUANG MIN-SHAN TSAI Wang, Chan-Chi WEI-TIEN CHANG SHING-HWA LIU WEN-JONE CHEN |
關鍵字: | apoptosis; autophagy; carbon dioxide; cardiac arrest; cerebral blood flow | 公開日期: | 十一月-2022 | 出版社: | WILEY | 卷: | 11 | 期: | 21 | 來源出版物: | Journal of the American Heart Association | 摘要: | Background Protracted cerebral hypoperfusion following cardiac arrest (CA) may cause poor neurological recovery. We hypothesized that inhaled carbon dioxide (CO2) could augment cerebral blood flow (CBF) and improve post-CA neurological outcomes. Methods and Results After 6-minute asphyxia-induced CA and resuscitation, Wistar rats were randomly allocated to 4 groups (n=25/group) and administered with different inhaled CO2 concentrations, including control (0% CO2), 4% CO2, 8% CO2, and 12% CO2. Invasive monitoring was maintained for 120 minutes, and neurological outcomes were evaluated with neurological function score at 24 hours post-CA. After the 120-minute experiment, CBF was 242.3% (median; interquartile range, 221.1%-267.4%) of baseline in the 12% CO2 group while CBF fell to 45.8% (interquartile range, 41.2%-58.1%) of baseline in the control group (P<0.001). CBF increased along with increasing inhaled CO2 concentrations with significant linear trends (P<0.001). At 24 hours post-CA, compared with the control group (neurological function score, 9 [interquartile range, 8-9]), neurological recovery was significantly better in the 12% CO2 group (neurological function score, 10 [interquartile range, 9.8-10]) (P<0.001) while no survival difference was observed. Brain tissue malondialdehyde (P=0.02) and serum neuron-specific enolase (P=0.002) and S100β levels (P=0.002) were significantly lower in the 12% CO2 group. TUNEL (terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling)-positive cell densities in hippocampal CA1 (P<0.001) and CA3 (P<0.001) regions were also significantly reduced in the 12% CO2 group. Western blotting showed that beclin-1 (P=0.02), p62 (P=0.02), and LAMP2 (lysosome-associated membrane protein 2) (P=0.01) expression levels, and the LC3B-II:LC3B-I ratio (P=0.02) were significantly lower in the 12% CO2 group. Conclusions Administering inhaled CO2 augmented post-CA CBF, mitigated oxidative brain injuries, ameliorated neuronal injury, and downregulated apoptosis and autophagy, thereby improving neurological outcomes. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/626897 | ISSN: | 2047-9980 | DOI: | 10.1161/JAHA.122.027685 |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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