Seizure-induced neutrophil adhesion in brain capillaries leads to a decrease in postictal cerebral blood flow

Cerebral hypoperfusion has been proposed as a potential cause of postictal neurological dysfunction in epilepsy, but its underlying mechanism is still unclear. We show that a 30% reduction in postictal cerebral blood flow (CBF) has two contributing factors: the early hypoperfusion up to ∼30 min post-seizure was mainly induced by arteriolar constriction, while the hypoperfusion that persisted for over an hour was due to increased capillary stalling induced by neutrophil adhesion to brain capillaries, decreased red blood cell (RBC) flow accompanied by constriction of capillaries and venules, and elevated intercellular adhesion molecule-1 (ICAM-1) expression. Administration of antibodies against the neutrophil marker Ly6G and against LFA-1, which mediates adhesive interactions with ICAM-1, prevented neutrophil adhesion and recovered the prolonged CBF reductions to control levels. Our findings provide evidence that seizure-induced neutrophil adhesion to cerebral microvessels via ICAM-1 leads to prolonged postictal hypoperfusion, which may underlie neurological dysfunction in epilepsy. [Display omitted] •Seizures caused an increased adhesion of neutrophils to brain capillaries•It led to an increased capillary stalling and a prolonged postictal hypoperfusion•The protein level of ICAM-1 was increased in the postictal mouse brains•Administering antibodies against Ly6G and LFA-1 resolved the prolonged hypoperfusion Biological sciences; Neuroscience; Neuroanatomy