We have been studying selected immunohistological patterns of intraventricular cerebellar allografts in host brains. It has been unclear why cerebellar grafts develop relatively normally without external inputs. We have attempted to determine what factors are essential for completion of their development and survival in host brains after implantation. Results indicate that the expression of cell adhesion molecules in transplanted cerebella is relatively undisturbed. Therefore, it is likely that the molecular mechanisms of granule cell migration are operant in grafts, independently of the normal inputs. Moreover, the data suggest that non-radially oriented glial-fibrillary acid protein--positive glia--may also be a substrate for migrating granule neurons in transplanted cerebella. Other results indicate that genetically normal cerebellar grafts can survive in a mutant host environment defective in cell-cell adhesion molecule and myelination. We have found that intraventricular grafts, as compared to intraparenchymal grafts, are bigger and do not produce large gliosis and demyelination of the host brain. The former, however, is not as well integrated with host brains in terms of presence of interconnecting neurites. The internal organization of both intraventricular and intraparenchymal grafts was relatively normal. We have also found that normal phosphorylation of neurofilaments occurs in cerebellar grafts in host tissue. Our results further suggest that, despite the rather similar enhancement of Ia immunoreactivity in host parenchyma (probably on microglia) after allo- and xenografting, only in xenografts does an intense host reaction occur that is capable of destroying transplanted tissue.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002428-01
Application #
3922050
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code