Enhancement of nigral graft survival in rat brain with the systemic administration of synthetic fibronectin peptide V

A major obstacle in neural transplantation is a severe loss of neurons in g rafts soon after implantation. In the present study. we have investigated w hether the systemic administration of synthetic fibronectin peptide V can i ncrease the survival of neural grafts. Synthetic fibronectin peptide V is d erived from the 33,000 mel. wt carboxyl-terminal heparin-binding domain of fibronectin. previous studies have shown that these polypeptides possess an ti-inflammatory properties. However, it is currently unknown whether this p eptide has anti-apoptotic properties. Dissociated neural grafts were prepar ed from the ventral mesencephalon of pregnant Sprague-Dawley rats and were stereotaxically injected as a cell suspension into the striatum of adult Sp rague-Dawley rats. A group of recipient rats received i.v, injections of pe ptide V (5 mg/kg, dissolved in saline) at 24 and 4 h prior to transplantati on, at the time of transplantation, and 24, 48 and 72 h post-transplantatio n. Saline-treated rats served as controls. The rats were killed at two, fou r and 42 days post-grafting and the brain tissue was immunologically proces sed for tyrosine-hydroxylase, major histocompatibility complex class I and class II antigens, complement receptor type 3 and leukocyte common antigen immunocytochemistry, and terminal deoxynucleotidyl transferase-mediated dUT P-biotin nick end labeling assay. We found a significant increase (approxim ately twofold) in the number of dopamine neurons in the grafts for the pept ide-treated group at four and 42 days compared with the controls. In contra st, there was no significant difference in the patterns of inflammation usi ng different immunocytochemical markers in the two different groups. The le vels of expression for these markers, however, were reduced over time. Inte restingly, the number of apoptotic cells in the graft areas was significant ly smaller in the peptide-treated group than in the control group two days after grafting. The results demonstrate that the systemic administration of synthetic fibro nectin peptide V can dramatically increase the survival of nigral grafts in the brain and substantially reduce the number of apoptotic cells in the gr aft site, suggesting that this peptide may exert a beneficial effect on sur vival of nigral grafts through an anti-apoptotic mechanism. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.