Department of Emergency Medicine, Dankook University Hospital, College of Medicine, Dankook University, Cheonan 31116, Chungnam, Korea.
Department of Emergency Medicine, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon 24289, Gangwon, Korea.
Int J Mol Sci. 2021 Dec 27;23(1):237. doi: 10.3390/ijms23010237.
In the present study, we investigated the neuroprotective effect of post-ischemic treatment with oxcarbazepine (OXC; an anticonvulsant compound) against ischemic injury induced by transient forebrain ischemia and its mechanisms in gerbils. Transient ischemia was induced in the forebrain by occlusion of both common carotid arteries for 5 min under normothermic conditions (37 ± 0.2 °C). The ischemic gerbils were treated with vehicle, hypothermia (whole-body cooling; 33.0 ± 0.2 °C), or 200 mg/kg OXC. Post-ischemic treatments with vehicle and hypothermia failed to attenuate and improve, respectively, ischemia-induced hyperactivity and cognitive impairment (decline in spatial and short-term memory). However, post-ischemic treatment with OXC significantly attenuated the hyperactivity and the cognitive impairment, showing that OXC treatment significantly reduced body temperature (to about 33 °C). When the hippocampus was histopathologically examined, pyramidal cells (principal neurons) were dead (lost) in the subfield Cornu Ammonis 1 (CA1) of the gerbils treated with vehicle and hypothermia on Day 4 after ischemia, but these cells were saved in the gerbils treated with OXC. In the gerbils treated with OXC after ischemia, the expression of transient receptor potential vanilloid type 1 (TRPV1; one of the transient receptor potential cation channels) was significantly increased in the CA1 region compared with that in the gerbils treated with vehicle and hypothermia. In brief, our results showed that OXC-induced hypothermia after transient forebrain ischemia effectively protected against ischemia-reperfusion injury through an increase in TRPV1 expression in the gerbil hippocampal CA1 region, indicating that TRPV1 is involved in OXC-induced hypothermia.
在本研究中，我们研究了氧代卡巴嗪（一种抗惊厥化合物）在短暂性前脑缺血后对缺血性损伤的神经保护作用及其在沙鼠中的机制。在体温正常（37±0.2°C）条件下，通过阻断双侧颈总动脉 5 分钟诱导前脑短暂性缺血。缺血性沙鼠用载体、低温（全身降温；33.0±0.2°C）或 200mg/kg 氧代卡巴嗪处理。载体和低温的缺血后处理未能减轻和改善缺血引起的过度活动和认知障碍（空间和短期记忆下降）。然而，氧代卡巴嗪的缺血后处理显著减轻了过度活动和认知障碍，表明氧代卡巴嗪治疗显著降低了体温（约 33°C）。当对海马进行组织病理学检查时，在缺血后第 4 天用载体和低温处理的沙鼠的 Cornu Ammonis 1（CA1）亚区中，锥体神经元（主要神经元）死亡（丢失），但在氧代卡巴嗪处理的沙鼠中这些细胞被保存下来。在缺血后用氧代卡巴嗪处理的沙鼠中，与用载体和低温处理的沙鼠相比，CA1 区中瞬时受体电位香草酸型 1（TRPV1；瞬时受体电位阳离子通道之一）的表达显著增加。总之，我们的结果表明，短暂性前脑缺血后氧代卡巴嗪诱导的低温通过增加沙鼠海马 CA1 区 TRPV1 的表达有效保护缺血再灌注损伤，表明 TRPV1 参与了氧代卡巴嗪诱导的低温。
