10% carbon dioxide improves cognitive function after subarachnoid hemorrhage in rats: inhibiting neuronal apoptosis through the PI3K/AKT signaling pathway.

Many patients experience long-term cognitive dysfunction after subarachnoid hemorrhage (SAH), and effective treatments are currently lacking. Carbon dioxide (CO2), 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 CO2 for therapeutic inhalation is still unclear. This study aimed to investigate the effects of various CO2 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 CO2 at concentrations of 10%, 20%, or 30%, for 1 hour after modeling. The results showed that inhalation of 10% CO2 improved cortical blood flow following SAH, while higher concentrations of CO2 (20% and 30%) worsened cortical hypoperfusion. The partial pressure of CO2 did not change 1 hour after SAH, but it significantly increased with the inhalation of 10% CO2. Additionally, 10% CO2 effectively inhibited neuronal apoptosis, enhanced locomotor activity, and improved memory and learning abilities in SAH rats. Moreover, 10% CO2 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% CO2 restores cerebral perfusion, inhibits neuronal apoptosis, and improves cognitive function in SAH rats. In contrast, higher concentrations of CO2 led to worsened hypoperfusion. The neuroprotective effect of 10% CO2 may occur through the activation of the phosphatidylinositol 3-kinase/protein kinase B signaling pathway.