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- Title
Risperidone Treatment after Transient Ischemia Induces Hypothermia and Provides Neuroprotection in the Gerbil Hippocampus by Decreasing Oxidative Stress.
- Authors
Yang, Go Eun; Tae, Hyun-Jin; Lee, Tae-Kyeong; Park, Young Eun; Cho, Jeong Hwi; Kim, Dae Won; Park, Joon Ha; Ahn, Ji Hyeon; Ryoo, Sungwoo; Kim, Young-Myeong; Shin, Myoung Cheol; Cho, Jun Hwi; Lee, Choong-Hyun; Hwang, In Koo; Jin, Hui; Won, Moo-Ho; Lee, Jae-Chul
- 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-HT2A receptor agonist), but not bromocriptine mesylate (a D2 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-HT2A 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.
- Subjects
INDUCED hypothermia; OXIDATIVE stress; GERBILS; BODY temperature; PYRAMIDAL neurons; HIPPOCAMPUS (Brain); NEUROGLIA
- Publication
International Journal of Molecular Sciences, 2019, Vol 20, Issue 18, p4621
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms20184621