Neuroprotection of postischemic hypothermia in combination with neuroprotective agents against ischemic neuronal damage

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Many animal experiments have indicated that postischemic hypothermia rescues neurons from transient ischemic damage. The neuroprotection of postischemic hypothermia depends on initiation time, duration, temperature, as well as the degree of ischemic damage. However, when the duration of hypothermia was only several hours and temperature was lowered only a few degrees, the neuroprotective effect of hypothermia was reduced in longer periods of survival. We examined whether short-duration or mild postischemic hypothermia in combination with neuroprotective agents treatment would consistently protect ischemic neuronal damage.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 CA1 neurons (60%) compared with the non-treated group (6%).γ-Glutamylethylamide (theanine) is contained in high-grade Japanese … More green tea as a natural glutamate analog. We examined the protective effect of theanine on ischemic delayed neuronal death in field CA1 of the gerbil hippocampus. One μl of theanine from each three concentrations (50 μM, 125 μM and 500 μM) was administered through the lateral ventricle 30 min before ischemia. Seven days after ischemia, the number of intact CA1 neurons in the hippocampus was assessed. Ischemic neuronal death in field CA1 of the hippocampus was significantly prevented in the theanine-pretreated groups in a dose-dependent manner, with approximately 60% and 90% survival with 125 μM and 500 μM of theanine, respectively. Moreover, we tested a protective effect of short-duration and mild hypothermia in combination with daily theanine treatment on delayed neuronal death in transient forebrain ischemia of gerbils. Theanine was administered daily 5 mg/kg after ischemia for 30 days. After survival of 30 days, the extent of CA1 neuronal damage in the hippocampus was assessed histologically. Short-duration and mild postischemic hypothermia combined with theanine treatment led to significant increase (67% and 72%, respectively) in viable CA1 neurons, compared to the control group (8% survival).These findings indicate that short-duration and mild hypothermia in combination with PPF or theanine has a beneficial effect on ischemic neuronal damage consistently. Less