|Authors||Liu, J., Reeves, C., Thomas, J., McEvoy, A., Miserocchi, A., Thompson, P., Sisodiya, S. and Thom, M.|
Nestin is expressed in immature neuroepithelial and progenitor cell types and transiently upregulated in proliferative neuroglial cells responding to acute brain injury, including following seizures. In 36 temporal lobe specimens from patients with temporal lobe epilepsy (age range 8-60 years) we studied the number, distribution and morphology of nestin-expressing cells in the pes, hippocampus body, parahippocampal gyrus, amygdala, temporal cortex and pole compared to post mortem control tissues from 26 cases (age range 12 gestational weeks to 76 years). The proliferative fraction of nestin-expressing cells was also evaluated in selected regions, including recognized niches, using MCM2. Their differentiation was explored with neuronal (DCX, mushashi, βIII tubulin, NeuN) and glial (GFAP, GFAPdelta, glutamine synthetase , aquaporin4) markers, both in sections and following culture. Findings were correlated with clinical parameters. A stereotypical pattern in the distribution and range of morphologies of nestin-expressing cells was observed, reminiscent of patterns in the developing brain, with increased densities in epilepsy compared to adult controls (p<0.001). Findings included MCM2-positive radial glial-like cells in the periventricular white matter and rows of nestin-expressing cells in the hippocampal fimbria and sulcus. Nestin cells represented 29% of the hippocampal proliferative fraction in epilepsy cases; 20% co-expressed βIII tubulin in culture compared to 28% with GFAP, but they mainly lacked glial maturation (aquaporin 4 or glutamine synthetase expression). Significant correlations were noted between age at surgery, memory deficits and NEC populations. Temporal lobe nestin-expressing cells with ongoing proliferative capacity likely represent vestiges of developmental migratory streams and resident reactive cell populations of potential relevance to hippocampal epileptogenesis, temporal lobe pathology and co-morbidities, including memory decline.