| Summary: | 碩士 === 國立成功大學 === 細胞生物及解剖學研究所 === 90 === The central nervous system (CNS) of the mammal is considered to be an immunologically privileged site because it lacks lymphatic drainage, and the brain is separated from the blood compartment by the blood-brain-barrier (BBB). It is generally believed that cytokines produced in the peripheral tissue can’t cross BBB because of the unique features of brain microvascular endothelial cells wrapped by end feet of astrocytes. There is now considerable information implicating many inflammatory conditions associated with neurodegeneration. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-administrated animal model of Parkinson’s disease seems to be a good model for studying neuroinflammation. As a rule, the normal brain blocks microglia from becoming too active, but an abnormal elevation of certain cytokines induced by MPTP can overcome the restraint and be quite harmful to dopaminergic neurons. Based on the preliminary data of M4 E.coli tracer with β-galactosidase activity, the vasopermeability of BBB can be changed by MPTP intoxication and then the immune privileged property of CNS can be alterable. We have investigated MPTP-induced glial response and proof of direct involvement of cytokines within short- and long-term neurotoxin damage. After different time courses with MPTP i.p. injection, the immuno- histochemical results show that in the striatum astrogliosis obviously was found from 3 to 30 day, and reached the highest with 1 to 2 weeks postinjury, while there is no significant change in the substantia nigra. Microgliosis in the substantia nigra and the striatum appeared as soon as 15hr after MPTP injection, then returned to the basal level about 1 month postinjury. However, the expressions of proinflammatory factor IL-1β, immune effector TNF-α, and immune modulator IFN-γ showed no significant difference between control and MPTP-injection groups as revealed by immunohistochemistry. The western blotting results of the expression of these cytokines were also unable to detect during glial activation. Thus, although glial activation can be induced by MPTP intoxication, the inflammatory features are considered to be associated with animal age and the extent of neuronal death.
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