| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2008: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
|
|---|
| Research Abstract |
Pro-inflammatory cytokines and NO are considered responsible for exacerbating brain injury. Activated microglia produce these potentially cytotoxic factors during neuron destruction. Therefore, the beneficial effects of therapeutic hypothermia on neuroprotection are considered to be due, in part, to suppression of post-injury inflammatory factors by microglia. In this study, I examined whether altering culture temperature modifies production of cytokines and NO by microglia activated with ATP, a product leaked from injured neurons/cells after brain insults. Compared to normothermia, hypothermia ecreased ATP-induced production of pro-inflammatory cytokines, TNF- α and IL-6, within 6 h of culture. NO production was reduced by hypothermia but augmented by hyperthermia at 6 h. In addition, activation of p38 MAPK was reduced in hypothermia at 1 min, compared to normothermia. In conclusion, hypothermia reduced the rapid activation of p38 MAPK and the following TNF-α, IL-6, and NO production in ATP-activated microglia, suggesting that the reduction of the early-phase inflammatory factors via suppression of p38 MAPK in microglia is one possible neuroprotective mechanism of therapeutic hypothermia. Hyperthermia specifically increased the early-phase NO production in these cells. These temperature-dependent changes in NO production may imply that NO in the early phase is useful as an important clinical marker in hypothermia-related neuronal protection and in hyperthermia-related neuronal injury.
|
