Methylprednisolone prevents rejection of intrastriatal grafts of xenogeneic embryonic neural tissue in adult rats.
We studied the effects of high-dose methylprednisolone on the survival of intrastriatal neural xenografts and the host responses against them. Dissociated mesencephalic tissue from inbred mouse (CBA-strain) embryos was transplanted to the intact striatum of adult Sprague-Dawley rats. The rats received either daily injections of methylprednisolone (30 mg/kg), or cyclosporin A (10 mg/kg), or no immunosuppressive treatment. Two or six weeks after transplantation, there was good survival of xenografts in both the methylprednisolone- and cyclosporin A-treated rats. In contrast, the xenografts in untreated control rats were all rejected by six weeks. There was no marked difference in the degree of expression of MHC class I and II antigens and the accumulation of activated astrocytes and microglial cells/macrophages between the three groups. However, both methylprednisolone and cyclosporin A reduced infiltration of T lymphocytes to the transplantation sites. The expression of pro-inflammatory cytokines (interferon-gamma, tumour necrosis factor-alpha, interleukin-6) in and around the grafts was lower in the methylprednisolone- and cyclosporin A-treated groups than in untreated control rats. Although high-dose methylprednisolone caused significant body weight loss, we conclude that this treatment can prevent rejection of intrastriatal grafts of xenogeneic embryonic neural tissue in the adult.
Duan
W M
WM
Brundin
P
P
Grasbon-Frodl
E M
EM
Widner
H
H
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D016380:Brain Tissue Transplantation / Q000276:immunology*; D016516:CD4-CD8 Ratio / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D016332:Fetal Tissue Transplantation / Q000276:immunology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008285:Major Histocompatibility Complex / Q000276:immunology; D008775:Methylprednisolone / Q000627:therapeutic use*; D051379:Mice; D017072:Neostriatum / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011951:Receptors, Complement / Q000276:immunology; D014183:Transplantation, Heterologous / Q000276:immunology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D007166:Immunosuppressive Agents; D011951:Receptors, Complement; D014446:Tyrosine 3-Monooxygenase; D008775:Methylprednisolone