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A novel, noninvasive, predictive epilepsy biomarker with clinical potential.

The Journal of neuroscience : the official journal of the Society for Neuroscience (2014-06-27)
ManKin Choy, Celine M Dubé, Katelin Patterson, Samuel R Barnes, Pamela Maras, Arlin B Blood, Anton N Hasso, Andre Obenaus, Tallie Z Baram
ABSTRACT

A significant proportion of temporal lobe epilepsy (TLE), a common, intractable brain disorder, arises in children with febrile status epilepticus (FSE). Preventative therapy development is hampered by our inability to identify early the FSE individuals who will develop TLE. In a naturalistic rat model of FSE, we used high-magnetic-field MRI and long-term video EEG to seek clinically relevant noninvasive markers of epileptogenesis and found that reduced amygdala T2 relaxation times in high-magnetic-field MRI hours after FSE predicted experimental TLE. Reduced T2 values likely represented paramagnetic susceptibility effects derived from increased unsaturated venous hemoglobin, suggesting augmented oxygen utilization after FSE termination. Indeed, T2 correlated with energy-demanding intracellular translocation of the injury-sensor high-mobility group box 1 (HMGB1), a trigger of inflammatory cascades implicated in epileptogenesis. Use of deoxyhemoglobin-sensitive MRI sequences enabled visualization of the predictive changes on lower-field, clinically relevant scanners. This novel MRI signature delineates the onset and suggests mechanisms of epileptogenesis that follow experimental FSE.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-HMGB1 (AB2) antibody produced in rabbit, IgG fraction of antiserum
Sigma-Aldrich
Anti-HMGB1 antibody produced in rabbit, affinity isolated antibody