title: Spatio-temporally restricted blood-brain barrier disruption after intra-amygdala kainic acid-induced status epilepticus in mice.
abstract: Mesial temporal lobe epilepsy (MTLE) is the most common, intractable seizure disorder in adults. Blood-brain barrier (BBB) disruption, including interruption of endothelial tight cell junctions and serum protein and immunoglobulin G (IgG) extravasation into brain parenchyma, has been reported in experimental and human MTLE and implicated in disease pathogenesis. Triggering status epilepticus in mice by intra-amygdala microinjection of kainic acid produces damage mainly within the CA3 subfield of the ipsilateral hippocampus, and recurrent spontaneous seizures emerge during the following week. To investigate whether BBB impairment is a feature of this model, we characterized endothelial tight cell junction proteins and IgG and albumin in the hippocampus up to three weeks after status epilepticus. Hippocampal microvessels displayed a reduction in continuous staining for zonula occludens 1 (ZO-1), the main tight junction protein, after status epilepticus and in epileptic mice, although western blotting found ZO-1 protein levels in the hippocampal subfields were not different from controls at any time. Increased IgG and albumin were detected in damaged and non-damaged ipsilateral hippocampal subfields, mainly 4-24h after status epilepticus, although increased serum protein extravasation was also found in the CA3 subfield in epileptic mice. Thus, BBB opening or damage occurs mainly in the period shortly after status epilepticus but may also persist within the CA3 subfield as a feature of the pathophysiology of chronic epilepsy in this model.
authors.affiliation: Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Zuzanna
authors.initials: Z
authors.lastname: Michalak
authors.forename: Takanori
authors.initials: T
authors.lastname: Sano
authors.forename: Tobias
authors.initials: T
authors.lastname: Engel
authors.forename: Suzanne F C
authors.initials: SF
authors.lastname: Miller-Delaney
authors.forename: Mireille
authors.initials: M
authors.lastname: Lerner-Natoli
authors.forename: David C
authors.initials: DC
authors.lastname: Henshall
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013226:Status Epilepticus / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D007608:Kainic Acid