Seizures cause sustained microvascular constriction associated with astrocytic and vascular smooth muscle Ca 2+ recruitment

Previously we showed that seizures result in a severe hypoperfusion/hypoxic attack that results in postictal memory and behavioral impairments (). However, neither postictal changes in microvasculature nor Ca changes in key cell-types controlling blood perfusion have been visualized , leaving essential components of the underlying cellular mechanisms unclear. Here we use two-photon microvascular and Ca 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 that was confined to the seizure period. Vascular smooth muscle cells displayed a significant increase in Ca 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.