Internal medicine

Cerebral blood flow

Neuroscience

Stroke (engine)

Central nervous system

Ischemia

Biology

Engineering

Blood flow

Endothelium

Blood–brain barrier

Reactive hyperemia

Medicine

Mechanical engineering

Potassium channel

Proceedings of the National Academy of Sciences

Significance Years before the emergence of infarctions or significant cognitive decline, patients with cerebral small vessel disease (SVD) show a deterioration in the ability of the brain to augment blood flow locally in response to increases in neuronal activity (functional hyperemia). Using a well-characterized genetic mouse model of a hereditary form of SVD, we determined the molecular defect at play in capillary endothelial cells. We found that SVD is associated with reduced synthesis of the phospholipid PIP 2 , which prevents the Kir2.1 channel-initiated capillary-to-arteriole electrical signaling that supports vasodilatory responses during functional hyperemia. We further show that systemic injection of exogenous PIP 2 is sufficient to rescue this deficit in SVD mice, restoring adequate cerebral blood flow in response to neuronal activation.

PIP <sub>2</sub> corrects cerebral blood flow deficits in small vessel disease by rescuing capillary Kir2.1 activity

PIP 2 corrects cerebral blood flow deficits in small vessel disease by rescuing capillary Kir2.1 activity

PIP ₂ corrects cerebral blood flow deficits in small vessel disease by rescuing capillary Kir2.1 activity