Impaired capillary-to-arteriolar electrical signaling after traumatic brain injury.

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 Ba2+-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.

• Authors: Amreen Mughal, Adrian M Sackheim, Maria Sancho, Thomas A Longden, Sheila Russell, Warren Lockette, Mark T Nelson, Kalev Freeman
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 41 Issue 6 Pg. 1313-1327 (06 2021) ISSN: 1559-7016 [Electronic] United States
• PMID: 33050826 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Kir2.1 channel
• Potassium Channels, Inwardly Rectifying

Topics

• Animals
• Arterioles (metabolism)
• Brain Injuries, Traumatic (physiopathology)
• Capillaries (metabolism)
• Cerebrovascular Circulation (physiology)
• Endothelial Cells (metabolism)
• Hemodynamics (physiology)
• Male
• Mice
• Mice, Inbred C57BL
• Potassium Channels, Inwardly Rectifying (metabolism)
• Signal Transduction (physiology)