Impaired capillary-to-arteriolar electrical signaling after traumatic brain injury. Issue 6 (June 2021)

• Record Type: Journal Article
• Authors: Mughal, Amreen; Sackheim, Adrian M; Sancho, Maria; Longden, Thomas A; Russell, Sheila; Lockette, Warren; Nelson, Mark T; Freeman, Kalev
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 41:Issue 6(2021)
• Page Start: 1313
• Page End: 1327
• Publication Date: 2021-06
• Subjects: Cerebral blood flow -- capillary endothelial cells -- functional hyperemia -- inward rectifier K+ channels (Kir2.1) -- traumatic brain injury; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1177/0271678X20962594
• Languages: English
• ISSNs: 0271-678X

Abstract

Traumatic brain injury (TBI) acutely impairs dynamic regulation of local cerebral blood flow, but long-term (>72 h) effects on functional hyperemia are unknown. Functional hyperemia depends on capillary endothelial cell inward rectifier potassium channels (Kir2.1) responding to potassium (K + ) released during neuronal activity to produce a regenerative, hyperpolarizing electrical signal that propagates from capillaries to dilate upstream penetrating arterioles. We hypothesized that TBI causes widespread disruption of electrical signaling from capillaries-to-arterioles through impairment of Kir2.1 channel function. We randomized mice to TBI or control groups and allowed them to recover for 4 to 7 days post-injury. We measured in vivo cerebral hemodynamics and arteriolar responses to local stimulation of capillaries with 10 mM K + using multiphoton laser scanning microscopy through a cranial window under urethane and α-chloralose anesthesia. Capillary angio-architecture was not significantly affected following injury. However, K + -induced hyperemia was significantly impaired. Electrophysiology recordings in freshly isolated capillary endothelial cells revealed diminished Ba 2+ -sensitive Kir2.1 currents, consistent with a reduction in channel function. In pressurized cerebral arteries isolated from TBI mice, K + failed to elicit the vasodilation seen in controls. We conclude that disruption of endothelial Kir2.1 channel function impairs capillary-to-arteriole electrical signaling, contributing to altered cerebral hemodynamics after TBI.