Progress in Transplantation Strategies for Temporal Lobe Epilepsy: Surgical and Neurochemical Influences on Seizure Threshold
Authors:Timothy Hong, Acacia Hori
Mentor:Kerry Thompson, Associate Professor of Biology, Occidental College
Hippocampal implants of cells genetically engineered to increase GABA levels have been shown to increase seizure thresholds in rat models of temporal lobe epilepsy. While it shows proof of principle, the effects reported to date have been modest and transient. In order to be clinically relevant, anti-seizure effects need to be enhanced. Research in cell-based therapy is currently challenged by limited graft survival, as well as cell death at the transplant site. Past transplantation methods have been shown to damage hilar granule cells, which are crucial to the functioning of hippocampal circuitry. To circumvent this damage, we transplanted either GABAergic or non-GABAergic cells into the hippocampi of ten adult male rats using a strategy designed to increase the number of transplanted cells yet avoid surgically-induced damage in the dentate gyrus. One week after transplantation, the rats were stimulated to determine their afterdischarge thresholds (ADT). This test revealed a drastic increase in threshold for both experimental and control groups. This effect of the surgical intervention itself showed partial abatement with longer survival times. We also investigated the effect of the surgical strategy itself by injecting vehicle instead of cells and testing for ADT. These data combined with our histological data suggest that transplantation strategies that greatly increase local concentrations of hippocampal GABA yet avoid granule cell losses can be developed.