| Co-Investigator(Kenkyū-buntansha) |
MORI Masaaki Yokohama City University School of Medicine, Medical Hospital, Lecturer, 医学部附属病院, 講師 (30254204)
AIHARA Yukoh Yokohama City University School of Medicine, Assistant Professor, 医学部附属市民総合医療センター, 助教授 (50211686)
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| Budget Amount *help |
¥11,900,000 (Direct Cost: ¥11,900,000)
Fiscal Year 2003: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2002: ¥7,000,000 (Direct Cost: ¥7,000,000)
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| Research Abstract |
The central nervous system (CNS) is an immune-privileged site by blood brain barrier (BBB). It is reported that glial cells such as microglia and astrocyte product cytokine in he CNS in normal and several disease states. Recent studies indicated that TNFa plays an important role in brain injury after various kind of insult (infection, ischemia, trauma). In this study, we established the experimental system of cytokine storm in the CNS by intracerabrospinal administration of lipopolysaccharide (LPS) and examined the effect of the proinflammatory cytokines in the CNS for brain and systemic. One hour after intracerabrospinal administration with LPS (30μg, 300μg), expression of IL-1^β, IL-6, TNFα mRNA was detected in rat brain by Rnase Protection Assay(RPA) and two hours after administration, cerebrospinal fluid(CSF) concentration of IL-1β, IL-6, TNFα increased. Histological examination proved activation of NFκB, apoptosis in rat brain, the description of blood brain barieer(BBB) by leak of FITC-Dextran(MW 10,000) from vessel in rat brain Serum concentration of IL-6, TNFα was increased by intracerebrospinal administration with high dose LPS. In conclusion, intracerebrospinal administration with LPS mediated activation of CNS immunosystem and production proinflammatory cytokine, such as IL-1β, IL-6, TNFα. Moreover, TNFα in the CNS mediated brain apoptosis and lead to BBB destruction. Finally peripheral cytokine concentration increased LPS and cytokine leaked through BBB.
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