In:
Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 41, No. 6 ( 2021-06), p. 1313-1327
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.
Type of Medium:
Online Resource
ISSN:
0271-678X
,
1559-7016
DOI:
10.1177/0271678X20962594
Language:
English
Publisher:
SAGE Publications
Publication Date:
2021
detail.hit.zdb_id:
2039456-1
