Transplants of embryonic brain tissue into injured adult brains have been successful in restoring function to the brain damaged animal. Transplants of brain cells from a different species can be as effective as tissue from the same species in restoring function. In the present study, transplants of mouse brain cells into lesioned rat brains will be made and the development of individual nerve cells described. This has not been possible before because the transplanted cells could not be adequately labeled. A technique will be used which will label the transplanted cells and will allow us to follow their development, growth, migration, and orientation in the host. The technique involves the incubation of the cell suspension with HRP. These studies will show how the transplanted cells become incorporated into the fabric of the host brain and will compare transplants between mouse and rat to transplants between rats. The label of the transplanted cells allows the same cells to be observed with both electron microscopy and light microscopy. The development of the synapses between host and donor cells can be observed. Hypotheses on the success of transplants can be tested, such as: xenogenic cells need to migrate further from the transplant injection site than homogenic cells in order to survive; and lesions are necessary to create available space on the host neurons to allow the donor to make synapses. The approach proposed here can be applied to many different kinds of neurobiological problems: Do the transplanted cells which come from the basal forebrain take on the appearance of cells in the host injection site which is the hippocampal formation? Is the growth of the axons and dendrites of the transplanted cells guided by host glia, neurons, or both? Are synapses formed early as the dendrites grow through the host tissue or only later on relatively mature dendrites? Basic studies such as proposed here will formulate neurobiological principles of development and synaptogenesis in the interaction between donor and host, as well as lay the ground work for future clinical applications of brain cell transplants for the recovery of function in brain damaged individuals.
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