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

Abstract

Previously 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 Ca ²⁺ 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 Ca ²⁺ 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 Ca ²⁺ that was confined to the seizure period. Vascular smooth muscle cells displayed a significant increase in Ca ²⁺ 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.

Highlights

• Seizures lead to equivalent levels of postictal hypoxia in both male and female mice

• Calcium elevation in astrocyte endfeet is confined to the seizure

• Postictal vasoconstriction in awake mice is mediated by cyclooxygenase-2

• Calcium elevation in vascular smooth muscle cells is enduring and correlates with vasoconstriction.