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Brain. 2017 Jun 1;140(6):1692-1705. doi: 10.1093/brain/awx073.

Imaging blood-brain barrier dysfunction as a biomarker for epileptogenesis.

Author information

Departments of Physiology and Cell Biology, Brain and Cognitive Sciences, Zlowotski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Department of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada.
Pediatric Neurology and Epilepsy, Pediatric Division, Soroka Medical Center, Beer-Sheva, Israel.
Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Department of Integrative Biology and the Helen Wills Neuroscience Institute, University of California, Berkeley, California, USA.
The Israel Defense Force Medical Corps, Tel Hashomer, Israel.
Sackler School of Medicine, Tel Aviv Uneversity, Tel Aviv, Israel.
NBC Protection Division, Ministry of Defense, Tel-Aviv, Israel.
The Institute for Research in Military Medicine, Hebrew University, Jerusalem, Israel.
Department of Industrial Engineering and Management, Ben-Gurion University of the Negev, Beer-Sheva, Israel.


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, P < 0.0001) 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.


biomarker; blood–brain barrier; epilepsy; magnetic resonance imaging

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