Fetal hippocampal CA3 cell grafts enriched with fibroblast growth factor-2 exhibit enhanced neuronal integration into the lesioned aging rat hippocampus in a kainate model of temporal lobe epilepsy.
Aging impairs the conduciveness of the lesioned hippocampus for robust survival of neurons derived from homotopic fetal cell grafts (Zaman and Shetty, Neuroscience 109:537-553, 2002), suggesting a need for graft augmentation in fetal graft-mediated therapeutic strategies for the lesioned aging hippocampus. We hypothesize that pretreatment and grafting of donor hippocampal CA3 cells with fibroblast growth factor-2 (FGF-2) considerably enhances graft neuronal integration into the lesioned CA3 region of the aging hippocampus. We employed the optical fractionator cell counting method and quantified the number of surviving cells and neurons derived from 5'-bromodoxyuridine-labeled embryonic day 19 CA3 cell grafts pre-treated and transplanted with FGF-2 into the lesioned CA3 region of the middle-aged and aged rat hippocampus at 4 days post-lesion. In both middle-aged and aged hippocampus, pre-treatment and transplantation of CA3 cell grafts with FGF-2 resulted in a robust yield of surviving cells (72-80% of injected cells) and neurons (62-69% of injected cells) from grafts. The overall yield was dramatically greater than the yield observed earlier from standard (untreated) fetal CA3 cell grafts into the lesioned aging hippocampus but was highly comparable to that observed for standard fetal CA3 cell grafts into the lesioned young hippocampus (Zaman and Shetty, Neuroscience 109:537-553, 2002). Thus, a robust neuronal integration from fetal CA3 cell grafts can be achieved into the lesioned CA3 region of the aging hippocampus with a simple pre-treatment and grafting of donor fetal CA3 cells with FGF-2. These results have implications toward the development of suitable cell grafting strategies for repair of the lesioned aging hippocampus in neurodegenerative diseases, particularly the temporal lobe epilepsy, stroke, and Alzheimer's disease.
Zaman
Vandana
V
Medical Research Service, Veterans Affairs Medical Center, Durham, North Carolina, USA.
Shetty
Ashok K
AK
D000818:Animals; D016380:Brain Tissue Transplantation / Q000379:methods*; D001973:Bromodeoxyuridine; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D005333:Fetus; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology* / Q000627:therapeutic use; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development / Q000601:surgery*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008569:Memory Disorders / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000637:transplantation; D010641:Phenotype; D051381:Rats; D011916:Rats, Inbred F344; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects
D016222:Fibroblast Growth Factor 2; D001973:Bromodeoxyuridine; D007608:Kainic Acid