Post-treatment with oxcarbazepine confers potent neuroprotection against transient global cerebral ischemic injury by activating Nrf2 defense pathway

Publication date: April 2020Source: Biomedicine & Pharmacotherapy, Volume 124Author(s): Cheol Woo Park, Ji Hyeon Ahn, Tae-Kyeong Lee, Young Eun Park, Bora Kim, Jae-Chul Lee, Dae Won Kim, Myoung Cheol Shin, Yoonsoo Park, Jun Hwi Cho, Sungwoo Ryoo, Young-Myeong Kim, Moo-Ho Won, Joon Ha ParkAbstractOxcarbazepine (OXC), a voltage-gated sodium channel blocker, is an antiepileptic medication and used for the bipolar disorders treatment. Some voltage-gated sodium channel blockers have been demonstrated to display strong neuroprotective properties in models of cerebral ischemia. However, neuroprotective effects and mechanisms of OXC have not yet been reported. Here, we investigated the protective effect of OXC and its mechanisms in the cornu ammonis 1 subfield (CA1) of gerbils subjected to 5 min of transient global cerebral ischemia (tGCI). tGCI led to death of most pyramidal neurons in CA1 at 5 days after ischemia. OXC (100 and 200 mg/kg) was intraperitoneally administered once at 30 min after tGCI. Treatment with 200 mg/kg, not 100 mg/kg OXC, significantly protected CA1 pyramidal neurons from tGCI-induced injury. OXC treatment significantly decreased superoxide anion production, 4-hydroxy-2-nonenal and 8-hydroxyguanine levels in ischemic CA1 pyramidal neurons. In addition, the treatment restored levels of superoxide dismutases, catalase, and glutathione peroxidase. Furthermore, the treatment distinctly inhibited tGCI-induced microglia activation and significantly reduced ...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research