Work

CO 2 inhalation enhances pericyte-mediated neurovascular protection in ischemic stroke and remains safe in hemorrhagic stroke

Year: 2026

Type: article

Abstract: Therapeutic options for acute ischemic stroke beyond reperfusion therapy are limited by narrow time windows and associated risks. Carbon dioxide (CO 2 ), a potent and adjustable vasodilator, may preserve ischemic brain tissue by enhancing cerebral blood flow (CBF) and stabilizing neurovascular components. We investigated whether CO 2 preconditioning prior to arterial occlusion confers neuroprotection in a transient middle cerebral artery occlusion (tMCAO) model and evaluated its safety in a collagenase-induced intracerebral hemorrhage (ICH) model. Adult male rats received 20% CO 2 before tMCAO or after ICH induction. In the tMCAO model, CO 2 preconditioning improved CBF, reduced infarct size, and enhanced neurological performance (Garcia score, modified Neurological Severity Score, and rotarod). At the cellular level, CO 2 preserved pericytes (platelet-derived growth factor receptor beta (PDGFRβ)), reduced oxidative stress (8-hydroxy-2′-deoxyguanosine (8-OHdG); matrix metalloproteinase-9 (MMP-9)), and maintained blood-brain barrier integrity (zonula occludens-1 (ZO-1), occludin, and claudin-5). In the ICH model, CO 2 did not exacerbate hematoma volume or neurological deficits, suggesting a favorable safety profile. Overall, these findings indicate that CO 2 preconditioning confers multifaceted neurovascular protection in ischemic stroke without increasing the risk of hemorrhagic complications. With its rapid onset, noninvasive delivery, and translational potential, CO 2 inhalation may serve as an early, prehospital intervention to improve stroke outcomes.

Source: Journal of Cerebral Blood Flow & Metabolism

DOI: 10.1177/0271678x261418929