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Imaging blood-brain barrier dysfunction as a biomarker for epileptogenesis
Guy Bar-Klein1, Svetlana Lublinsky1, Lyn Kamintsky2
1Departments of Physiology and Cell Biology, Brain and Cognitive Sciences, Zlowotski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Brain : a Journal of Neurology
|April 27, 2017
Summary
Identifying high-risk epilepsy patients is crucial. Early blood-brain barrier damage predicts epilepsy, and treatments like anesthesia or losartan can prevent it, showing promise for a new biomarker.
Area of Science:
- Neuroscience
- Biomarker Discovery
- Epilepsy Research
Background:
- Acquired epilepsy risk stratification requires reliable biomarkers.
- Microvascular pathology, blood-brain barrier (BBB) dysfunction, and neuroinflammation are linked to epileptogenesis.
- Current methods lack predictive accuracy for post-injury epilepsy.
Purpose of the Study:
- To identify a predictive biomarker for post-injury epilepsy.
- To quantitatively assess blood-brain barrier (BBB) pathology as a potential biomarker.
- To evaluate the therapeutic potential of interventions targeting BBB dysfunction.
Main Methods:
- Prospective, longitudinal magnetic resonance imaging (MRI) in rats post-status epilepticus.
- Quantitative assessment of BBB pathology.
- Late electrocorticography (ECoG) for epilepsy diagnosis.
- Post-mortem immunohistochemistry for BBB and neuroinflammation confirmation.
- Testing anti-epileptogenic effects of isoflurane anesthesia and losartan.
Main Results:
- Early BBB pathology in the piriform network accurately predicted epilepsy (AUC=0.96, P<0.0001).
- Diffuse BBB pathology correlated with lower epilepsy risk.
- Isoflurane anesthesia and losartan prevented early microvascular damage and subsequent epilepsy.
- BBB dysfunction and neuroinflammation were confirmed post-mortem.
Conclusions:
- Quantitative assessment of BBB pathology is a sensitive and specific predictor of acquired epilepsy.
- Early BBB damage is a key factor in epileptogenesis.
- Targeting early BBB pathology with interventions like isoflurane or losartan shows therapeutic potential.
- This BBB assessment could serve as a predictive, diagnostic, and pharmacodynamic biomarker for acquired epilepsy.
