| 研究概要 |
Therapeutic hypothermia after an ischemic insult is the most potent neuroprotective strategies. The currently used physical methods for hypothermia induction show some complications due to the body's response to heat loss. To avoid these side effects focal brain cooling may be an alternative. An ideal approach for prompt and efficient hypothermia induction immediately after ischemia onset may be the usage of pharmacological compounds. In the first part, we investigated the transient receptor potential vanilloid-1 (TRPV1) for fast, efficient drug-induced hypothermia. We examined the effect of TRPV1 endogenous agonist(OLDA) in healthy rats and analyzed its effect on body and brain. We identified that a single dose of OLDA leads to a significant decrease in brain temperature to a minimum of 34.2±0.6°C, and body temperature 34.5±0.5°C. Both temperatures remained within the optimal range for therapeutic hypothermia for 2 h. In the second part of our study, we examined an approach for focal brain cooling using a Peltier device. Our device was able to rapidly reduce intracranial temperature to 34°C and was maintained constant without altering body temperature. To analyze the neuroprotective effect of 2h focal brain cooling we used the photothrombosis model and determined the infarction volume 24h post ischemia. We see a reduction on infarct size. The combination of these two cooling methods may be considered as an potential approach in clinical use, since it may provide promptly induced, prolonged hypothermia overcoming the side effects of systemic hypothermia.
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