Neural transplantation is well recognized as an important experimental and clinical method for studying problems in neurobiology. The broad long-term objectives of this proposal are to determine the morphological and physiological nature of blood vascular and humoral connectivity between host and graft. Specifically, in the experimental transplantation models attempts will be made to elucidate the nature of alterations in the blood- brain barrier (BBB) and blood-CSF barrier. These models utilize both adrenal medulla and fetal CNS tissue grafts. A major hypothesis is that adrenal medulla, due to its intrinsic vascular permeability can act as a biological portal and permit blood-borne compounds to gain access into the brain and CSF of hosts where normally they would be excluded. These experiments will lay groundwork to investigate not only of whether host-graft connectivity potentially may be affected by vascular neuroactive agents but if normal, fluid homeostasis is altered. To accomplish these aims transplant-bearing rats will receive vascular injections of protein or radiolabeled neurotransmitter and histochemistry, immunohistochemistry and in vivo autoradiography will be performed to determine if both graft and host neurons have access to specific exogenous compounds. CSF content will be evaluated by immuno- affinity chromatography for immunoglobulin. In fetal CNS tissues, further studies will examine specific parameters of BBB deficiency. These include the use of a new monoclonal antibody, endothelial Brain Antigen, for BBB-competent vessels, localization of insulin receptors in brain grafts, and the appearance of certain cellular immunological responses such as the deposition of immune by products (complexes). In addition the functional metabolic and developmental states of grafted neurons will be examined by localization of Neuron Specific Enolase and receptors for growth and vascular related peptides will be examined using in vitro autoradiography. The results of these and future studies will elucidate aspects of BBB properties in neural transplants and may be important for comparisons with certain neurological states when the 888 is compromised.
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