Abstracts

Rationale: Hippocampal specimens obtained from mesial temporal lobe epilepsy (TLE, MTLE) surgery provide an excellent opportunity to study human memory-related pathology. Extensive preoperative memory assessments are available for correlation to histopathological analysis of resected hippocampi. IAT memory testing offers the unique possibility to access memory performance of each isolated hippocampus by intracarotid amobarbital anaesthesia. Additionally, verbal memory capacity could be related to the left hippocampus. Methods: 1) In 24 patients with unilateral TLE declarative memory function were correlated to cell densities in the different hippocampal CA subfields and the dentate gyrus (DG), using IAT. 2) The neurogenic potential in the human DG could be investigated by isolating adult human neural stem cells from 23 surgical en bloc hippocampus resections. 3) In 75 unilateral TLE patients memory profiles were related to different patterns of neuronal cell loss in MTLE, i.e. to selective loss of CA1 pyramidal cells versus other MTS patterns. Results: 1) Multiple regression and partial correlation analyses identified neuronal cell loss within the internal limb of the dentate gyrus, a developmentally distinct subregion of the hippocampal formation known to generate new neurons throughout life, as highly significant predictor for the patient s ability to learn and recall memories (p<0.01). 2) After proliferation of the progenitor cell pool in vitro two distinct patterns were identified: adult neural stem cells with a high proliferation capacity (HPC) were obtained in 11 patients, most of these cells were capable of neuronal differentiation. In 12 specimens a low proliferation capacity (LPC) were obtained with reduced numbers of proliferating cells in vivo. HPC and LPC groups differed considerably in declarative memory tasks, with normal memory performance in HPC and severe impairment in LPC (r=0.813; p<0.001). 3) Selective CA1 neuronal loss did not associate with memory deficits, either with IAT memory deficits, nor with verbal memory deficits compared to other MTS subtypes with cell loss in all hippocampal subfields and highly reduced memory capacities (p< 0.001 / (p<0.05).