Table 1.

The neuroprotective effects of carbon dioxide (CO₂) in stroke

Study	Model	Main results	Species
Yokoyama et al.26	SAH	Both the maximum and minimum PaCO2 levels during intensive care unit management in patients with SAH were significantly associated with unfavorable neurological outcomes.	Human
Vannucci et al.20	MCAO	Mild hypercapnia (~54 mmHg induced by 6% CO2 inhalation in immature rats) preserved cerebral blood flow during hypoxia-ischemia, improved oxidative metabolism and inhibited glutamate secretion.	Rats
Miller et al.27 Nakagawa et al.28	MCAO	Mild hypercapnia (PaCO2 of 45–70 mmHg) hastens the post-ischemia recovery of cortical electrical activity.	Rats
Vannucci et al.29	MCAO	In immature hypoxic-ischemic rats, exposure to 15% CO2 (mean PaCO2 of 100 mmHg) induced more brain damage than did exposure to lower CO2 concentrations.	Rats
Katsura et al.30 Ekholm et al.31	MCAO	Severe hypercapnia may aggravate neuronal injury by inducing marked extra- and intra-cellular acidosis and/or impaired cell calcium hemostasis.	Rats
Paljärvi et al.32	MCAO	Short-term, moderate hypercapnia (PaCO2 of 150 mmHg for 45 min) has no effect on neuronal ultrastructures in anesthetized rats, severe hypercapnia (PaCO2 of 300 mmHg) results in the coarsening of nuclear chromatin, mitochondrial swelling and disruption of polyribosomes.	Rats

Note: MCAO: Middle cerebral artery occlusion; PaCO2: partial pressure of carbon dioxide; SAH: subarachnoid hemorrhage.