| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Outline of Final Research Achievements |
Microglia represent rational but difficult therapeutic targets for stroke due to their diverse phenotypes that play dual-faced protective (M2 phenotype) and toxic (M1 phenotype) effects. Melatonin injection increased the level of Interleukin-4（IL-4）, the best known M2 inducing cytokine. Melatonin significantly reduced infarct volume and attenuated sensorimotor deficits. IL-4 deficiency, abolished melatonin-afforded long term protection. Melatonin-treated mice showed significantly reduced expression of inflammatory cytokine and chemokines, with significantly increased expression of M2 markers and decreased expression of M1 markers. Melatonin inhibited LPS (a M1 inducer)-induced production of NO and TNFα, confirming that melatonin has direct anti-inflammatory effect on microglia. Melatonin may represent an innovative therapeutic strategy that shifts microglia polarization toward a protective M2 phenotype in an IL-4-dependent manner and thus enhance long-term recovery after stroke.
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