Abstract
Compelling evidence from preclinical and clinical studies has shown that mild hypothermia is neuroprotective against ischemic stroke. We investigated the neuroprotective effect of post-risperidone (RIS) treatment against transient ischemic injury and its mechanisms in the gerbil brain. Transient ischemia (TI) was induced in the telencephalon by bilateral common carotid artery occlusion (BCCAO) for 5 min under normothermic condition (37 ± 0.2 °C). Treatment of RIS induced hypothermia until 12 h after TI in the TI-induced animals under uncontrolled body temperature (UBT) compared to that under controlled body temperature (CBT) (about 37 °C). Neuroprotective effect was statistically significant when we used 5 and 10 mg/kg doses (p < 0.05, respectively). In the RIS-treated TI group, many CA1 pyramidal neurons of the hippocampus survived under UBT compared to those under CBT. In this group under UBT, post-treatment with RIS to TI-induced animals markedly attenuated the activation of glial cells, an increase of oxidative stress markers [dihydroethidium, 8-hydroxy-2' -deoxyguanosine (8-OHdG), and 4-Hydroxynonenal (4-HNE)], and a decrease of superoxide dismutase 2 (SOD2) in their CA1 pyramidal neurons. Furthermore, RIS-induced hypothermia was significantly interrupted by NBOH-2C-CN hydrochloride (a selective 5-HT(2A) receptor agonist), but not bromocriptine mesylate (a D(2) receptor agonist). Our findings indicate that RIS-induced hypothermia can effectively protect neuronal cell death from TI injury through attenuation of glial activation and maintenance of antioxidants, showing that 5-HT(2A) receptor is involved in RIS-induced hypothermia. Therefore, RIS could be introduced to reduce body temperature rapidly and might be applied to patients for hypothermic therapy following ischemic stroke.