Predicting novel histopathological microlesions in human epileptic brain through transcriptional clustering

Fabien Dachet, Shruti Bagla, Gal Keren-Aviram, Andrew Morton, Karina Balan, Laleh Saadat, Tibor Valyi-Nagy, William Kupsky, Fei Song, Edward Dratz, Jeffrey A. Loeb
2014 Brain  
Although epilepsy is associated with a variety of abnormalities, exactly why some brain regions produce seizures and others do not is not known. We developed a method to identify cellular changes in human epileptic neocortex using transcriptional clustering. A paired analysis of high and low spiking tissues recorded in vivo from 15 patients predicted 11 cell-specific changes together with their 'cellular interactome'. These predictions were validated histologically revealing millimetre-sized
more » ... crolesions' together with a global increase in vascularity and microglia. Microlesions were easily identified in deeper cortical layers using the neuronal marker NeuN, showed a marked reduction in neuronal processes, and were associated with nearby activation of MAPK/CREB signalling, a marker of epileptic activity, in superficial layers. Microlesions constitute a common, undiscovered layer-specific abnormality of neuronal connectivity in human neocortex that may be responsible for many 'non-lesional' forms of epilepsy. The transcriptional clustering approach used here could be applied more broadly to predict cellular differences in other brain and complex tissue disorders.
doi:10.1093/brain/awu350 pmid:25516101 pmcid:PMC4306820 fatcat:vnolbmblyvhuhje2btqz4sstra