Neuroinflammation imaging markers for epileptogenesis

Abstract

Epilepsy can be a devastating disorder. In addition to debilitating seizures, epilepsy can cause cognitive and emotional problems with reduced quality of life. Therefore, the major aim is to prevent the disorder in the first place: identify, detect, and reverse the processes responsible for its onset, and monitor and treat its progression. Epilepsy often occurs following a latent period of months to years (epileptogenesis) as a consequence of a brain insult, such as head trauma, stroke, or status epilepticus. Although this latent period clearly represents a therapeutic window, we are not able to stratify patients at risk for long-term epilepsy, which is prerequisite for preventative clinical trials. Moreover, because of the length of the latent period, an early biomarker for treatment response would be of high value. Finally, mechanistic biomarkers of epileptogenesis may provide more profound insight in the process of disease development.

Neuroinflammation in neocortical epilepsy measured by PET imaging of translocator protein

“…24 Previous studies have shown increased TSPO binding in several ep ilepsy syndromes. 24 Previous studies have shown increased TSPO binding in several ep ilepsy syndromes.…”

Ex vivo characterization of neuroinflammatory and neuroreceptor changes during epileptogenesis using candidate positron emission tomography biomarkers

“…29,30 Here, we describe the evolution of tracer binding to mGluR5, GABA A receptors, and microglia and astroglia markers during epileptogenesis and chronic epilepsy in the lithium-pilocarpine post-SE model in rats. Imaging biomarkers are of great interest as they enable several in vivo measurement in a minimally invasive manner and allow visualization of molecular pathways involved in epileptogenesis.…”

“…Imaging biomarkers are of great interest as they enable several in vivo measurement in a minimally invasive manner and allow visualization of molecular pathways involved in epileptogenesis. 29,30 Here, we describe the evolution of tracer binding to mGluR5, GABA A receptors, and microglia and astroglia markers during epileptogenesis and chronic epilepsy in the lithium-pilocarpine post-SE model in rats. The use of in vitro autoradiography enabled direct quantification and comparison of all tracers in brain slices from the same animals for each time point.…”

Pharmacological targeting of brain inflammation in epilepsy: Therapeutic perspectives from experimental and clinical studies

“…This would allow patient stratification to test the candidate anti-inflammatory drugs and for designing affordable and adequately powered antiepileptogenesis trials, and to monitor treatment response. In this context, much progress has been made and several noninvasive inflammation-related humoral 44,[146][147][148][149] (blood/cerebrospinal fluid) and imaging measures [150][151][152][153][154][155][156][157] have been identified ( Table 2). Such biomarkers could be used to increase the sensitivity and precision of the available clinical indicators.…”