Blood-brain barrier dysfunction and epilepsy: Pathophysiologic role and therapeutic approaches

Nicola Marchi, Tiziana Granata, Chaitali Ghosh, Damir Janigro

Research output: Contribution to journalArticle

Abstract

The blood-brain barrier (BBB) is located within a unique anatomic interface and has functional ramifications to most of the brain and blood cells. In the past, the BBB was considered a pharmacokinetic impediment to antiepileptic drug penetration into the brain; nowadays it is becoming increasingly evident that targeting of the damaged or dysfunctional BBB may represent a therapeutic approach to reduce seizure burden. Several studies have investigated the mechanisms linking the onset and sustainment of seizures to BBB dysfunction. These studies have shown that the BBB is at the crossroad of a multifactorial pathophysiologic process that involves changes in brain milieu, altered neuroglial physiology, development of brain inflammation, leukocyte-endothelial interactions, faulty angiogenesis, and hemodynamic changes leading to energy mismatch. A number of knowledge gaps, conflicting points of view, and discordance between clinical and experimental data currently characterize this field of neuroscience. As more pieces are added to this puzzle, it is apparent that each mechanism needs to be validated in an appropriate clinical context. We now offer a BBB-centric view of seizure disorders, linking several aspects of seizures and epilepsy physiopathology to BBB dysfunction. We have reviewed the therapeutic, antiseizure effect of drugs that promote BBB repair. We also present BBB neuroimaging as a tool to correlate BBB restoration to seizure mitigation. Add-on cerebrovascular drug could be of efficacy in reducing seizure burden when used in association with neuronal antiepileptic drugs.

Original languageEnglish
Pages (from-to)1877-1886
Number of pages10
JournalEpilepsia
Volume53
Issue number11
DOIs
Publication statusPublished - Nov 2012

Keywords

  • Blood-brain barrier
  • Brain homeostasis
  • Brain-periphery axis
  • Glucocorticosteroids
  • Inflammation

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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