Purpose: To evaluate survival, differentiation and migration of adult neural progenitor cells (aNPCs) after transplantation in a sclerotic hippocampus. Methods: aNPCs isolated from the subventricular zone (SVZ) of transgenic green fluorescent protein (GFP) mice were transplanted in intact and sclerotic hippocampi of respectively normal rats and rats with temporal lobe epilepsy after intrahippocampal injection of kainic acid (KA). aNPCs were transplanted 3 days and 3 weeks after KA injection. Rats were sacrificed 3 or 6 weeks after transplantation. Results: The total number of surviving GFP expressing cells 3 and 6 weeks after transplantation, was estimated to be ~1% of the number of transplanted cells in all groups. The survival rate was significantly higher when aNPCs were transplanted 3 days after KA injection compared to transplantation 3 weeks after KA injection. Migration of the cells was higher in intact hippocampi and did not change over time. The majority of the GFP positive cells expressed GFAP, a protein expressed by astrocytes. In the sclerotic hippocampi, there was a significantly higher differentiation towards astrocytes (50-70%) compared to non-sclerotic hippocampi (30-40%). Only a low percentage of cells differentiated towards neurons. Conclusions: We found that aNPCs isolated from SVZ survive long term as astrocyte-like cells in a sclerotic hippocampus. These results combined with the fact that aNPCs are an accessible, expandable, storable and multipotent cell source make that this cell type, engineered to secrete seizure-modifying substances, could be used for future cell therapy approaches to treat medically intractable seizures.