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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

1
Departments of Physiology and Cell Biology, Brain and Cognitive Sciences, Zlowotski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
2
Department of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada.
3
Pediatric Neurology and Epilepsy, Pediatric Division, Soroka Medical Center, Beer-Sheva, Israel.
4
Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
5
Department of Integrative Biology and the Helen Wills Neuroscience Institute, University of California, Berkeley, California, USA.
6
The Israel Defense Force Medical Corps, Tel Hashomer, Israel.
7
Sackler School of Medicine, Tel Aviv Uneversity, Tel Aviv, Israel.
8
NBC Protection Division, Ministry of Defense, Tel-Aviv, Israel.
9
The Institute for Research in Military Medicine, Hebrew University, Jerusalem, Israel.
10
Department of Industrial Engineering and Management, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

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, 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.

KEYWORDS:

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

PMID:
28444141
DOI:
10.1093/brain/awx073
[Indexed for MEDLINE]

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