Prolonged postlesion transplantation delay adversely influences survival of both homotopic and heterotopic fetal hippocampal cell grafts in kainate-lesioned CA3 region of adult hippocampus

Fetal hippocampal CA3 cell grafts exhibit dramatically enhanced survival wh en transplanted at an early postlesion delay of 4 days into the lesioned CA 3 region of adult hippocampus. However, survival of these homotopic grafts following placement at late postlesion time points when the host milieu is considerably less receptive to grafts is unknown. We hypothesize that an ex tended postlesion delay at the rime of grafting will lead to significant di minution in cell survival of both homotopic and heterotopic fetal transplan ts grafted to lesioned adult CNS. We quantitatively investigated absolute c ell survival of 5'-bromodroxyuridine-labeled fetal hippocampal CA3 and CA1 cell grafts, following transplantation into the lesioned CA3 region of adul t rat hippocampus, at a delay of 45 days after a unilateral intracerebroven tricular administration of kainic acid (KA). Survival of these grafts was a lso analyzed in intact CA3 of the hippocampus contralateral to KA administr ation for comparison. In lesioned CR3 region, CA3 (homotopic) and CA1 (hete rotopic) grafts exhibited comparable but only moderate survival, with a rec overy of only 21-31% of injected cells. Cell survival in these grafts into lesioned hippocampus was similar to survival of grafts placed into the cont ralateral intact CA3 region. These results are in sharp contrast to increas ed graft survival measured following transplants performed at 4 days postle sion. in such grafts placed early, there was both a significantly higher ce ll survival than grafts placed into the intact CA3 region and also a charac teristic differential survival based on graft cell specificity to the lesio ned CA3 region (Zaman et al., Exp. Neurol., 161:535-561, 2000). Thus, the e nhanced conduciveness of lesioned CA3 region for survival of homotopic CA3 cell grafts observed at 4 days postlesion wanes by 45 days postlesion to th at of intact CA3 region, in spite of residual loss of CA3 neurons with the lesion. Strategies that considerably augment graft cell survival may theref ore be critical for optimal integration of fetal grafts into the adult CNS at late postlesion time points.