Fetal hippocampal CA3 cell grafts transplanted to lesioned CA3 region of the adult hippocampus exhibit long-term survival in a rat model of temporal lobe epilepsy.
Intracerebroventricular administration of kainic acid in the adult rat, a widely used model for studying human temporal lobe epilepsy, results in widespread degeneration of CA3-pyramidal neurons. Transplantation of specific fetal hippocampal CA3 cell grafts into the lesioned CA3-region at a prolonged post lesion delay of 45-day leads to 31% graft cell survival at 1 month postgrafting and significantly facilitates appropriate recovery of the lesioned host hippocampus. However, the capability of hippocampal CA3 cell grafts for enduring survival in this model is unknown. We hypothesize that a significant fraction of fetal CA3 cells grafted into the lesioned CA3 region of the adult hippocampus at 45-days postlesion exhibit long-term survival. We measured the extent of cell survival within 5'-bromodeoxyuridine-labeled CA3 cell grafts at 1 year postgrafting, following their transplantation at 45 days postlesion into the lesioned CA3-region. Quantification of absolute graft cell survival using BrdU immunostaining and the optical fractionator counting method revealed survival of 36% of grafted cells at 1 year postgrafting. Thus, over a third of fetal hippocampal CA3 cells transplanted to the lesioned CA3-region at 45 days postlesion exhibit long-term survival. Further, the extent of cell survival in these grafts is highly analogous to the degree of cell survival in CA3 grafts analyzed earlier at 1 month postgrafting, suggesting that specific fetal cells that survive the first month of grafting into the lesioned CNS area are capable of exhibiting enduring survival.
Zaman
V
V
Medical Research Service, Veterans Affairs Medical Center, Durham, North Carolina 27705, USA.
Shetty
A K
AK
D000375:Aging / Q000502:physiology; D000818:Animals; D015415:Biomarkers; D016380:Brain Tissue Transplantation / Q000379:methods*; D001973:Bromodeoxyuridine; D002452:Cell Count; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000473:pathology / Q000601:surgery*; D016332:Fetal Tissue Transplantation / Q000379:methods*; D006085:Graft Survival / Q000502:physiology*; D006624:Hippocampus / Q000473:pathology / Q000601:surgery* / Q000637:transplantation*; D007150:Immunohistochemistry; D007608:Kainic Acid; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000601:surgery; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000637:transplantation*; D017966:Pyramidal Cells / Q000166:cytology / Q000637:transplantation; D051381:Rats; D011916:Rats, Inbred F344
D015415:Biomarkers; D009419:Nerve Tissue Proteins; D001973:Bromodeoxyuridine; D007608:Kainic Acid