Risperidone Treatment after Transient Ischemia Induces Hypothermia and Provides Neuroprotection in the Gerbil Hippocampus by Decreasing Oxidative Stress

• Published in: International journal of molecular sciences Vol. 20; no. 18; p. 4621
• Main 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
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 18.09.2019; MDPI
• Subjects: 5-HT2A antagonist; Animals; antipsychotic drug; Antipsychotics; Body temperature; Brain injury; Brain Ischemia - drug therapy; Brain Ischemia - metabolism; Brain Ischemia - pathology; delayed neuronal death; Drug dosages; Gerbillinae; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; Hypothermia; Hypothermia - chemically induced; Hypothermia, Induced - methods; Ischemia; ischemia/reperfusion; Male; Morphology; Neuroprotection; Neuroprotection - drug effects; Neuroprotective Agents - therapeutic use; Oxidative stress; Oxidative Stress - drug effects; post-treatment; Psychotropic drugs; Risperidone; Risperidone - therapeutic use; Serotonin S2 receptors; Stroke; Thermoregulation; delayed neuronal death; ischemia/reperfusion; antipsychotic drug; post-treatment; 5-HT2A antagonist; thermoregulation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20184621

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 ( < 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 receptor agonist), but not bromocriptine mesylate (a D 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 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.