Seizures cause sustained microvascular constriction associated with astrocytic and vascular smooth muscle Ca2+ recruitment

Abstract

AbstractPreviously we showed that seizures result in a severe hypoperfusion/hypoxic attack that results in postictal memory and behavioral impairments (Farrell et al., 2016). However, neither postictal changes in microvasculature nor Ca2+ changes in key cell-types controlling blood perfusion have been visualized in vivo, leaving essential components of the underlying cellular mechanisms unclear. Here we use two-photon microvascular and Ca2+ imaging in awake mice to show that seizures result in a robust vasoconstriction of cortical penetrating arterioles, which temporally mirrors the prolonged postictal hypoxia. The vascular effect was dependent on cyclooxygenase-2, as pre-treatment with ibuprofen prevented postictal vasoconstriction. Seizures caused a rapid elevation in astrocyte endfoot Ca2+ that was confined to the seizure period. Vascular smooth muscle cells displayed a significant increase in Ca2+ both during and following seizures, lasting up to 75 minutes. The temporal activities of two cell-types within the neurovascular unit lead to seizure-induced hypoxia.HighlightsSeizures lead to equivalent levels of postictal hypoxia in both male and female miceCalcium elevation in astrocyte endfeet is confined to the seizurePostictal vasoconstriction in awake mice is mediated by cyclooxygenase-2Calcium elevation in vascular smooth muscle cells is enduring and correlates with vasoconstriction.