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Neurological disease

Unsticking for seizure prevention

Nature Reviews Drug Discovery volume 8, page 22 (2009)Cite this article

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Using a mouse model of epilepsy, Fabene and colleagues have found that epileptic seizures increase the interaction of leukocytes with blood-vessel walls, leading to inflammation and damage to the blood–brain barrier. Although previous data have suggested a role for brain inflammation in epilepsy, none of the current epilepsy treatments addresses the inflammatory component of the disease.

The authors show that pilocarpine-induced acute seizure activity in mice increases the expression of leukocyte adhesion molecules — such as mucin P-selectin glycoprotein ligand 1(PSGL1), α4β1 and αLβ2 integrins, and vascular cell adhesion molecule 1 (VCAM1) — in the vasculature. Prior administration of the CNS depressant diazepam — which suppresses the induced seizures — prevented the increase in expression of VCAM1 in brain blood vessels, indicating that neuronal hyperactivity contributes to this upregulation.

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ORIGINAL RESEARCH PAPER

  1. Fabene, P.F. et al. A role for leukocyte—endothelial adhesion mechanisms in epilepsy. Nature Med. 23 Nov 2008 (doi:10.1038/nm.1878)

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Authors
  1. Monica Hoyos Flight
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Flight, M. Unsticking for seizure prevention. Nat Rev Drug Discov 8, 22 (2009). https://doi.org/10.1038/nrd2787

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