Abstracts

Rationale: Despite overwhelming evidence for the presence of stem cells in the adult brain, these cells do not produce neurons after brain injury. This is true even in the permissive niche of the hippocampus where new neurons, important for memory consolidation, are normally produced throughout life. We wished to examine the hypothesis that the injured environment of in the sclerotic hippocampus of epileptic patients reprograms these stem cells and see if this was reversible Methods: We isolated neural stem cells from normal cortex and from the sclerotic hippocampus in 5 patients undergoing epilepsy surgery. Stem cells were either grown as free-floating spheres in an ideal environment or within a 3D tissue (Hi-Spot) generated from the hippocampus or cortex, and their ability to generate neurons quantified using BrdU and Neu-N immunohistochemistry. Results: We show that stem cells from the uninjured cortex and the sclerotic (injured) hippocampus generate new neurons with equal efficiency when grown under ideal free-floating conditions. Interestingly, the numbers of newly-born neurons generated by matched stem cells grown in sclerotic hippocampal Hi-Spots were significantly lower (one fourth) than those of the cortical Hi-Spots. Conclusions: These results strongly implicate the microenvironment in defective hippocampal stem cell function in areas of chronic epilepsy, and importantly from the viewpoint of brain repair, show that the effect is reversible.