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

Abstract

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.