Neural transplantation, increasingly, is a major tool for studying questions in neurobiology. This research project will study transplant functionality from the perspective of fluid environments; the blood vascular system and the cerebrospinal fluid (CSF). The major hypothesis contends that neural transplantation serves to permanently alter homeostasis of the brain; circulating neuroactive substances, such as protein or neurotransmitters, might gain access to normally non-accessible brain areas. The exchange of cellular elements, such as endothelium, between host and transplant may change the normal functional properties of the Blood-Brain Barrier (BBB). THe longer term objectives are to understand mechanisms in BBB development and alterations in neural transplants and how it might alter the brain's fluid environment. Lack of BBB properties should expose both host and transplant to compounds, either naturally occurring or administered, that are normally sequestered from brain tissue.
One specific aim of the project is to determine if autonomic tissue transplants exist as a portal into the brain and CSF in that the passage of blood-borne proteins or neurotransmitters is facilitated at the transplant site. A further objective is to determine if transplants from the fetal CNS develop basic characteristics of a mature BBB; preliminary data for this project suggest they do not. Using several methodologies including protein and fluorescent histochemistry, gel electrophoresis, immunocytochemistry, in vivo autoradiography and 2-deoxy-D-glucose technique, this project will attempt to determine if CNS transplants retain normal or altered criteria for protein and amine permeability, cerebral microvessel characteristics, glucose utilization and certain peptide receptors. The results of these and future studies of this research program not only may elucidate aspects of BBB development but may be important for comparisons with other model systems of BBB breakdown such as head trauma, hypertension or brain tumor induction.
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