Jun Hwi Cho
Kangwon National University, Republic of Korea
Title: Risperidone treatment after transient ischemia induces hypothermia via 5-HT2a antagonism and provides neuroprotection in the gerbil hippocampus by decreasing oxidative stress
Biography
Biography: Jun Hwi Cho
Abstract
Purpose: Compelling evidence from preclinical and clinical studies has shown that mild hypothermia is neuroprotective against ischemic stroke. We investigated neuroprotective effect of post-risperidone (RIS) treatment against transient ischemic injury and its mechanisms in the gerbil brain.
Materials and methods: Transient ischemia (TI) was induced in the telencephalon by bilateral common carotid artery occlusion (BCCAO) for 5 min under normothermic condition (37 ± 0.2ºC). Post-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 37ºC).
Results: 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, increases of oxidative stress markers (dihydroethidium, 8-OHdG and 4-HNE), and a decrease of superoxide dismutase 2 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).
Conclusions: 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.
Recent Publications:
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Jung YS, Kim KS, Suh GJ, Cho JH (2019) Pre-Comparison between Gel Pad Cooling Device and Water Blanket during Target Temperature Management in Cardiac Arrest Patients. Acute Crit Care 33(4):246-251.
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Lee CH, Park JH, Ahn JH, Kim JD, Cho JH, Lee TK, Won MH (2019) Stronger antioxidant enzyme immunoreactivity of Populus tomentiglandulosa extract than ascorbic acid in rat liver and kidney. Iran J Basic Med Sci 22(8):963-967.
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Lee TK, Kim H, Song M, Lee JC, Park JH, Ahn JH, Yang GE, Kim H, Ohk TG, Shin MC, Cho JH, Won MH (2019) Time-course pattern of neuronal loss and gliosis in gerbil hippocampi following mild, severe, or lethal transient global cerebral ischemia. Neural Regen Res 14(8):1394-1403.
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Lee JH, Jung JY, Lee HJ, Kim DK, Kwak YH, Chang I, Kwon H, Choi YJ, Park JW, Paek SH, Cho JH (2019) Efficacy of low-dose nebulized epinephrine as treatment for croup: A randomized, placebo-controlled, double-blind trial. Am J Emerg Med 37(12):2171-2176.
- Ahn JH, Ohk TG, Kim DW, Kim H, Song M, Lee TK, Lee JC, Yang GE, Shin MC, Cho JH, Choi SY, Won MH, Park JH (2019) Fluoro-Jade B histofluorescence staining detects dentate granule cell death after repeated five-minute transient global cerebral ischemia. Metab Brain Dis 34(3):951-956.