Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5736312 | Brain Research Bulletin | 2017 | 32 Pages |
Abstract
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.
Keywords
STAT3PFHSRSsCXCR2IL6CXCL1MAP2AEDsTLEIL8FITCGFAPDMSOERK1/2ElectroencephalogramInterleukin-8interleukin-6EpilepsySeizuresspontaneous recurrent seizuresantiepileptic drugsCNSDimethylsulfoxidecentral nervous systemtemporal lobe epilepsyfluorescein isothiocyanatesignal transducer and activator of transcription 3EEGparaformaldehydeGlial fibrillary acidic proteinmicrotubule-associated protein 2Pilocarpineextracellular signal-regulated kinase 1/2
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Authors
Tao Xu, Xinyuan Yu, Teng Wang, Ying Liu, Xi Liu, Shu Ou, Yangmei Chen,