Increased endothelial calcium signals in cerebral vessels following traumatic brain injury

Abstract

Traumatic brain injury (TBI) can cause impairment in cerebrovascular function. Endothelial cell (EC) Ca2+ signals normally activate both nitric oxide (NO) and endothelium‐derived hyperpolarizing factor (EDHF) vasodilatory pathways in cerebral arteries. Little is currently known about the impact of brain injury on vascular endothelial Ca2+ signaling. We studied the effects of TBI on EC and Ca2+ signals in rat basilar arteries. Arteries were harvested 24h after fluid percussion injury or sham surgery. We measured EC Ca2+ signals in slit‐opened basilar arteries from TBI and control animals using the Ca2+ fluorophore Fluo2‐leakage resistant and confocal microscopy. We found that localized EC Ca2+ signals were elevated in TBI animals. The optical waveforms of these events were consistent with two Ca2+ signaling modalities: 1) Ca2+ pulsars—mediated via endoplasmic reticulum Ca2+ release through inositol trisphosphate receptors and 2) Ca2+ sparklets—caused by Ca2+ entry through Ca2+permeable channel (e.g. TRPV4 channels) in the EC plasma membrane. The frequency of both types of EC Ca2+ signaling events were elevated after TBI. These data suggest that altered EC Ca2+ signaling may play a role in abnormal cerebrovascular function after TBI.