RT Journal Article
T1 Impaired capillary-to-arteriolar electrical signaling after traumatic brain injury
A1 Mughal, Amreen
A1 Sackheim, Adrian M.
A1 Sancho González, María
A1 Longden, Thomas A.
A1 Russell, Sheila
A1 Lockette, Warren
A1 Nelson, Mark T.
A1 Freeman, Kalev
AB 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.
PB SAGE Publications
SN 0271-678X
YR 2021
FD 2021-06
LK https://hdl.handle.net/20.500.14352/109909
UL https://hdl.handle.net/20.500.14352/109909
LA eng
NO Mughal A, Sackheim AM, Sancho M, Longden TA, Russell S, Lockette W, Nelson MT, Freeman K. Impaired capillary-to-arteriolar electrical signaling after traumatic brain injury. J Cereb Blood Flow Metab. 2021. 41(6):1313-1327. doi: 10.1177/0271678X20962594.
NO American Heart Association
NO Department of Defense/The Henry M. Jackson Foundation for the Advancement of Military Medicine
NO National Institutes of Health
NO Unión Europea
NO Foundation Leducq
NO Totman Medical Research Trust
DS Docta Complutense
RD 20 abr 2025