|Budget Amount *help
¥3,100,000 (Direct Cost : ¥3,100,000)
Fiscal Year 1998 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1997 : ¥2,200,000 (Direct Cost : ¥2,200,000)
Many animal experiments have indicated that postischemic hypothermia rescues neurons from transient ischemic damage. The neuroprotection of postischernic hypothermia depends on initiation time, duration, temperature, as well as the degree of ischemic damage. We evaluated the neuroprotective effect of posuischemic hypothermia on ischemic damage in gerbils. Hypothermia initiated 1 hr for 11 or 23 hrs produced significant protection of CAl neurons, compared with the non-treated group. Hypothermia of 23 hrs duration greatly protected CAl neurons from death. A marked protection of CAl neurons was still observed even when hypothermia was initiated up to S hrs after ischemia. When the duration of hypothermia initiated 6 hrs after ischemia was prolonged to 24 hrs or 48 hrs after ischemia, the number of Cal neurons increased. Temperatures of hypothermia less than 35ﾟC (1-24 hr) were significantly neuroprotective against ischemic damage.
In the non-treated group, lectin-positive microglia first a
ppeared 6 h after ischemia, and the strongest microglial reactions were observed 4 days after ischemia. In the short-duration (5h) postischemic hypothermia group, neuroprotections against ischemic neuronal damages were observed 7days after ischemia : However, strong microglial reactions were also observed in the short-duration postischemic hypothermia group, and most of the CAl neurons had disappeared 30 days after ischemia. In the long-duration (23h) postischemic hypothermia group, the microglial reaction was reduced throughout until 30 days after ischemia.
Propentofylline (PPF) is known to have an inhibitory effect of microglial proliferation. Short-duration postischemic hypothermia combined with daily PPF (10 mg/kg, ip, for 2 weeks) treatment led to a significant increase in the number of normal CAl neurons (60%) compared with the non-treated group (6%).
These findings indicated that the mechanisms of neuroprotection of postischemic hypothermia is partially involved in the suppression of the microglial activation after transient ischemia and that PPF has a beneficial effect on ischemic neuronal damages in the late periods after reperfusion.
in addition, we tested the neuroprotection of postischemic hypothermia in rat MCA occlusion models (lh, intraluminal method). When hypothermia started at 2, 4 or 6 h after reperfusion, the cerebral cortex infarct volume in the hypothermia group significantly decreased compared with the non-treated group. These data suggest that postischemic hypothermia is a beneficial means for cerebral protection against ischemic damages. Less