Mughal, AmreenSackheim, Adrian M.Sancho González, MaríaLongden, Thomas A.Russell, SheilaLockette, WarrenNelson, Mark T.Freeman, Kalev2024-11-042024-11-042021-06Mughal 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: 10.1177/0271678X20962594.0271-678X10.1177/0271678X20962594https://hdl.handle.net/20.500.14352/109909Traumatic 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.engjournal article1559-7016https://doi.org/10.1177/0271678X20962594https://journals.sagepub.com/doi/10.1177/0271678X20962594?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmedrestricted access612Cerebral blood flowcapillary endothelial cellsfunctional hyperemiainward rectifier K+ channels (Kir2.1)traumatic brain injuryCiencias Biomédicas24 Ciencias de la Vida