Imaging blood-brain barrier dysfunction as a biomarker for epileptogenesis

Guy Bar-Klein, Svetlana Lublinsky, Lyn Kamintsky, Iris Noyman, Ronel Veksler, Hotjensa Dalipaj, Vladimir V. Senatorov, Evyatar Swissa, Dror Rosenbach, Netta Elazary, Dan Z. Milikovsky, Nadav Milk, Michael Kassirer, Yossi Rosman, Yonatan Serlin, Arik Eisenkraft, Yoash Chassidim, Yisrael Parmet, Daniela Kaufer, Alon Friedman

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

A biomarker that will enable the identification of patients at high-risk for developing post-injury epilepsy is critically required. Microvascular pathology and related blood-brain barrier dysfunction and neuroinflammation were shown to be associated with epileptogenesis after injury. Here we used prospective, longitudinal magnetic resonance imaging to quantitatively follow blood-brain barrier pathology in rats following status epilepticus, late electrocorticography to identify epileptic animals and post-mortem immunohistochemistry to confirm blood-brain barrier dysfunction and neuroinflammation. Finally, to test the pharmacodynamic relevance of the proposed biomarker, two anti-epileptogenic interventions were used; isoflurane anaesthesia and losartan. Our results show that early blood-brain barrier pathology in the piriform network is a sensitive and specific predictor (area under the curve of 0.96, P50.0001) for epilepsy, while diffused pathology is associated with a lower risk. Early treatments with either isoflurane anaesthesia or losartan prevented early microvascular damage and late epilepsy. We suggest quantitative assessment of blood-brain barrier pathology as a clinically relevant predictive, diagnostic and pharmaco!dynamics biomarker for acquired epilepsy.

Original languageEnglish
Pages (from-to)1692-1705
Number of pages14
JournalBrain
Volume140
Issue number6
DOIs
StatePublished - 1 Jun 2017

Keywords

  • Biomarker
  • Blood-brain barrier
  • Epilepsy
  • Magnetic resonance imaging

ASJC Scopus subject areas

  • Clinical Neurology

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