Seizure-induced brain-borne inflammation sustains seizure recurrence and blood–brain barrier damage
Version of Record online: 23 JUL 2012
Copyright © 2012 American Neurological Association
Annals of Neurology
Volume 72, Issue 1, pages 82–90, July 2012
How to Cite
Librizzi, L., Noè, F., Vezzani, A., de Curtis, M. and Ravizza, T. (2012), Seizure-induced brain-borne inflammation sustains seizure recurrence and blood–brain barrier damage. Ann Neurol., 72: 82–90. doi: 10.1002/ana.23567
- Issue online: 23 JUL 2012
- Version of Record online: 23 JUL 2012
- Accepted manuscript online: 24 FEB 2012 09:17AM EST
- Manuscript Accepted: 17 FEB 2012
- Manuscript Revised: 24 JAN 2012
- Manuscript Received: 15 SEP 2011
Epilepsy is a common neurological disorder characterized by recurrent seizures often unresponsive to pharmacological treatment. Brain inflammation is considered a crucial etiopathogenetic mechanism of epilepsy that could be targeted to control seizures. Specific inflammatory mediators overexpressed in human epileptogenic foci are known to promote seizures in animal models. We investigated whether seizures induce brain inflammation independently on extracerebral factors. We also investigated whether brain-borne inflammation is required and sufficient to maintain seizure activity and whether it causes blood–brain barrier (BBB) impairment. We addressed these questions by studying the relation between seizures, inflammation, and BBB permeability in a brain preparation isolated from extracerebral compartments.
Epileptiform activity was induced by arterial perfusion of bicuculline in the in vitro isolated guinea pig brain. Seizure-induced brain inflammation was evaluated by quantitative immunohistochemical analysis of interleukin (IL)-1β in parenchymal cells. BBB damage was assessed by extravasation of intravascular fluorescein isothiocyanate–albumin. The effects of arterially perfused anakinra, a human recombinant IL-1β receptor antagonist, were investigated on epileptiform discharges, brain inflammation, and BBB damage.
Seizure induction in the absence of extracerebral factors promoted the release of IL-1β from brain resident cells and enhanced its biosynthesis in astrocytes. Anakinra rapidly terminated seizures, prevented their recurrence, and resolved seizure-associated BBB breakdown.
Seizures initiate brain inflammation in glia and promote BBB damage that is independent of either leukocytes or blood-borne inflammatory molecules. Brain inflammation contributes to the duration and recurrence of seizures. This study supports the use of specific anti-inflammatory drugs in clinical conditions that present with intractable recurrent seizures. ANN NEUROL 2012;72:82–90