Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, China.
Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, China.
Brain Res Bull. 2017 Sep;134:91-98. doi: 10.1016/j.brainresbull.2017.07.003. Epub 2017 Jul 10.
C-X-C motif chemokine receptor 2 (CXCR2) is one of the most well characterized chemokine receptors and is a potential target for treating brain pathologies involving inflammatory processes, including epilepsy. However, the role of CXCR2 in epilepsy has not been investigated, and whether CXCR2 modulates seizure activity in temporal lobe epilepsy (TLE) remains unknown. In this study, we aimed to determine the potential role of CXCR2 in intractable TLE patients and in pilocarpine-induced epileptic mice. Here, through Western blotting and semi-quantitative immunohistochemistry, we detected that CXCR2 protein expression was up-regulated (by nearly 50%) in the temporal neocortex of TLE patients and in the hippocampus and adjacent temporal cortex of pilocarpine mice model. Double-label immunofluorescence and immunohistochemical analysis indicated that CXCR2 was expressed in neurons. To investigate the effect of the CXCR2 selective antagonist SB225002 on seizure activity, SB225002 was i.p. administered during the latency window of spontaneous recurrent seizures (SRSs). This treatment increased (by nearly 40%) the latency of SRSs and reduced (by nearly 50%) the frequency of SRSs during the chronic period of epilepsy. This study suggests that CXCR2 plays a critical role in modifying epileptic seizure activity and that CXCR2 blockade could be a potential molecular therapeutic target for epilepsy.
C-X-C 基序趋化因子受体 2（CXCR2）是最具特征性的趋化因子受体之一，是治疗涉及炎症过程的脑病理学的潜在靶点，包括癫痫。然而，CXCR2 在癫痫中的作用尚未得到研究，CXCR2 是否调节颞叶癫痫（TLE）中的癫痫发作活动仍不清楚。在这项研究中，我们旨在确定 CXCR2 在耐药性 TLE 患者和匹罗卡品诱导的癫痫小鼠中的潜在作用。在这里，通过 Western blot 和半定量免疫组织化学，我们检测到 TLE 患者的颞叶皮质和匹罗卡品小鼠模型的海马和相邻颞叶皮质中 CXCR2 蛋白表达上调（接近 50%）。双标记免疫荧光和免疫组织化学分析表明 CXCR2 表达于神经元中。为了研究 CXCR2 选择性拮抗剂 SB225002 对癫痫发作活动的影响，在自发性复发性癫痫发作（SRSs）的潜伏期窗口期间通过腹腔内给予 SB225002。这种治疗方法使 SRS 的潜伏期增加（接近 40%），并使癫痫慢性期 SRS 的频率降低（接近 50%）。本研究表明，CXCR2 在调节癫痫发作活动中起关键作用，CXCR2 阻断可能是癫痫的潜在分子治疗靶点。
