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Prolonged Postlesion Transplantation Delay Adversely Influences Survival of Both Homotopic and Heterotopic Fetal Hippocampal Cell Grafts in Kainate-Lesioned CA3 Region of Adult Hippocampus

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Abstract:

Fetal hippocampal CA3 cell grafts exhibit dramatically enhanced survival when transplanted at an early postlesion delay of 4 days into the lesioned CA3 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 extended postlesion delay at the time of grafting will lead to significant diminution in cell survival of both homotopic and heterotopic fetal transplants grafted to lesioned adult CNS. We quantitatively investigated absolute cell survival of 5′-bromodeoxyuridine-labeled fetal hippocampal CA3 and CA1 cell grafts, following transplantation into the lesioned CA3 region of adult rat hippocampus, at a delay of 45 days after a unilateral intracerebroventricular administration of kainic acid (KA). Survival of these grafts was also analyzed in intact CA3 of the hippocampus contralateral to KA administration for comparison. In lesioned CA3 region, CA3 (homotopic) and CA1 (heterotopic) grafts exhibited comparable but only moderate survival, with a recovery of only 21–31% of injected cells. Cell survival in these grafts into lesioned hippocampus was similar to survival of grafts placed into the contralateral intact CA3 region. These results are in sharp contrast to increased graft survival measured following transplants performed at 4 days postlesion. In such grafts placed early, there was both a significantly higher cell survival than grafts placed into the intact CA3 region and also a characteristic differential survival based on graft cell specificity to the lesioned CA3 region (Zaman et al., Exp. Neurol., 161:535-561, 2000). Thus, the enhanced conduciveness of lesioned CA3 region for survival of homotopic CA3 cell grafts observed at 4 days postlesion wanes by 45 days postlesion to that of intact CA3 region, in spite of residual loss of CA3 neurons with the lesion. Strategies that considerably augment graft cell survival may therefore be critical for optimal integration of fetal grafts into the adult CNS at late postlesion time points.

Keywords: Graft cell survival; Graft integration; Hippocampus; Kainic acid; Key words: 5′-Bromodeoxyuridine; Neural transplantation

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/000000001783986963

Affiliations: Medical Research and Surgery (Neurosurgery) Services, Veterans Affairs Medical Center, Durham, NC 27705

Publication date: February 1, 2001

More about this publication?
  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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