Department of Anesthesiology, the Second Affiliated Hospital of Harbin Medical University, the Hei Long Jiang Province key Lab of Research on Anesthesiology and Critical Care Medicine, Harbin 150081, China.
Brain Res. 2013 Oct 2;1533:52-62. doi: 10.1016/j.brainres.2013.08.014. Epub 2013 Aug 11.
Recent studies have demonstrated neuroprotective effects of therapeutic hypercapnia for different forms of brain injury. However, few studies have assessed the neuroprotective and neurobehavioral effects of hypercapnia in focal cerebral ischemia, and the underlying mechanisms are still unclear. Here, we investigated the effects of therapeutic hypercapnia in focal cerebral ischemia in the rat middle cerebral artery occlusion/reperfusion (MCAO/R) model. Adult male Sprague Dawley rats were subjected to 90 min of MCAO/R and subsequently exposed to increased carbon dioxide (CO2) levels to maintain arterial blood CO2 tension (PaCO2) between 80 and 100 mmHg for 2h. Neurological deficits were evaluated with the corner test at days 1, 7, 14, and 28. Infarction volume and apoptotic changes were assessed by 2, 3, 7-triphenyltetrazolium chloride (TTC) staining, and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL) staining at 24h after reperfusion. Apoptosis-related proteins (Bcl-2, Bax, cytochrome c, and caspase-3) were investigated by western blotting. The results of this study showed that therapeutic hypercapnia significantly reduced infarct volume and improved neurological scores after MCAO/R. Moreover, hypercapnia treatment increased the survival rate at 28 days after reperfusion. The TUNEL-positive neurons in the ipsilateral cortex were significantly decreased in the hypercapnia group. Mitochondrial Bcl-2 and Bax cortical expression levels were significantly higher and lower, respectively, in hypercapnia-treated rats. In addition, hypercapnia treatment decreased cytosolic cytochrome c and cleaved caspase-3 expression and increased cytosolic Bax expression. These findings indicate that therapeutic hypercapnia preserves brain tissue and promotes functional neurological recovery through antiapoptotic mechanisms.
最近的研究表明，治疗性高碳酸血症对不同形式的脑损伤具有神经保护作用。然而，很少有研究评估高碳酸血症对局灶性脑缺血的神经保护和神经行为学影响，其潜在机制仍不清楚。在这里，我们研究了治疗性高碳酸血症对大鼠大脑中动脉闭塞/再灌注（MCAO/R）模型局灶性脑缺血的影响。成年雄性 Sprague Dawley 大鼠接受 90 分钟 MCAO/R，随后暴露于高浓度二氧化碳（CO2）中，将动脉血 CO2 张力（PaCO2）维持在 80-100mmHg 2 小时。在第 1、7、14 和 28 天通过转角试验评估神经功能缺损。通过 2,3,7-三苯基四氮唑氯化物（TTC）染色和再灌注后 24 小时末端脱氧核苷酸转移酶介导的 2'-脱氧尿苷 5'-三磷酸生物素 nick 末端标记（TUNEL）染色评估梗死体积和凋亡变化。通过 Western blot 检测凋亡相关蛋白（Bcl-2、Bax、细胞色素 c 和 caspase-3）。这项研究的结果表明，治疗性高碳酸血症可显著减少 MCAO/R 后的梗死体积并改善神经评分。此外，高碳酸血症治疗可提高再灌注后 28 天的存活率。高碳酸血症组同侧皮质中的 TUNEL 阳性神经元明显减少。高碳酸血症治疗大鼠皮质中线粒体 Bcl-2 和 Bax 表达水平明显升高和降低，分别。此外，高碳酸血症治疗可降低胞浆细胞色素 c 和裂解 caspase-3 表达，增加胞浆 Bax 表达。这些发现表明，治疗性高碳酸血症通过抗凋亡机制保护脑组织并促进功能神经恢复。
