Tang Liuyang, Wen Daochen, Huang Zichao, Lei Xingwei, Li Xiaoguo, Zhu Yajun, Hai Su, Guo Zongduo
Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Neurosurgery, Yongchuan Hospital of Chongqing Medical University, Chongqing, China.
Med Gas Res. 2025 Sep 1;15(3):391-397. doi: 10.4103/mgr.MEDGASRES-D-24-00116. Epub 2025 Mar 12.
Many patients experience long-term cognitive dysfunction after subarachnoid hemorrhage (SAH), and effective treatments are currently lacking. Carbon dioxide (CO 2 ), an inexpensive and easily produced gas, forms carbonic acid when dissolved in water. Studies have suggested that hypercapnia may have neuroprotective effects. However, the optimal concentration of CO 2 for therapeutic inhalation is still unclear. This study aimed to investigate the effects of various CO 2 concentrations on cognitive function in SAH rats and to explore the potential molecular mechanisms involved. In this study, we established a rat model of SAH by endovascular perforation of the internal carotid artery. The rat models inhaled CO 2 at concentrations of 10%, 20%, or 30%, for 1 hour after modeling. The results showed that inhalation of 10% CO 2 improved cortical blood flow following SAH, while higher concentrations of CO 2 (20% and 30%) worsened cortical hypoperfusion. The partial pressure of CO 2 did not change 1 hour after SAH, but it significantly increased with the inhalation of 10% CO 2 . Additionally, 10% CO 2 effectively inhibited neuronal apoptosis, enhanced locomotor activity, and improved memory and learning abilities in SAH rats. Moreover, 10% CO 2 upregulated the phosphorylation of phosphatidylinositol 3 kinase) and protein kinase B, increased the expression of Bcl-2, and decreased the expression of Bax. In conclusion, inhaling 10% CO 2 restores cerebral perfusion, inhibits neuronal apoptosis, and improves cognitive function in SAH rats. In contrast, higher concentrations of CO 2 led to worsened hypoperfusion. The neuroprotective effect of 10% CO 2 may occur through the activation of the phosphatidylinositol 3-kinase/protein kinase B signaling pathway.
许多患者在蛛网膜下腔出血（SAH）后会经历长期的认知功能障碍，而目前缺乏有效的治疗方法。二氧化碳（CO₂）是一种廉价且易于产生的气体，溶于水时会形成碳酸。研究表明，高碳酸血症可能具有神经保护作用。然而，用于治疗性吸入的最佳CO₂浓度仍不清楚。本研究旨在探讨不同浓度的CO₂对SAH大鼠认知功能的影响，并探索其潜在的分子机制。在本研究中，我们通过颈内动脉血管内穿刺建立了SAH大鼠模型。建模后，大鼠模型吸入浓度为10%、20%或30%的CO₂，持续1小时。结果显示，吸入10%的CO₂可改善SAH后的皮质血流，而较高浓度的CO₂（20%和30%）则会加重皮质灌注不足。SAH后1小时，CO₂分压没有变化，但吸入10%的CO₂后显著升高。此外，10%的CO₂有效抑制了SAH大鼠的神经元凋亡，增强了运动活动，并改善了记忆和学习能力。而且，10%的CO₂上调了磷脂酰肌醇3激酶和蛋白激酶B的磷酸化水平，增加了Bcl-2的表达，并降低了Bax的表达。总之，吸入10%的CO₂可恢复脑灌注，抑制神经元凋亡，并改善SAH大鼠的认知功能。相比之下，较高浓度的CO₂会导致灌注不足加重。10%的CO₂的神经保护作用可能是通过激活磷脂酰肌醇3激酶/蛋白激酶B信号通路实现的。
