Altered Expression Of CXCL13 And CXCR5 In Intractable Temporal Lobe Epilepsy Patients And Epileptic Rats

Objective:The mechanisms that underlie the pathogenesis of epilepsy are still unclear.Recent studies have indicated that inflammatory processes occurring in the brain are involved in a common and crucial mechanism in epileptogenesis.C-X-C motif chemokine ligand 13(CXCL13)and its only receptor,C-X-C motif chemokine receptor 5(CXCR5),are highly expressed in the central nervous system(CNS)and participate in inflammatory responses.The present study aimed to assess the expression of CXCL13 and CXCR5 in the brain tissues of both patients with intractable epilepsy(IE)and a rat model(lithium-pilocarpine)of temporal lobe epilepsy(TLE)to identify possible roles of the CXCL13-CXCR5 signaling pathway in epileptogenesis.Methods:1.Twenty temporal neocortex samples of patients with TLE and twenty histologically normal temporal neocortex samples of patients with brain trauma were obtained.2.SD rats were injected intraperitoneally with lithium-pilocarpine to establish chronic epilepsy model.The rats in control group were injected with normal saline.3.Double-labeled immunofluorescence analysis was conducted to determine the cellular distribution of CXCL13 and CXCR5 in the brain tissues of the TLE patients and TLE rats.The mRNA and protein expression of CXCL13 and CXCR5 of each group were measured by Real-time quantitative polymerase chain reaction(RT-qPCR),immunohistochemical and Western blot.Results:Double-labeled immunofluorescence analysis revealed that CXCL13 was mainly expressed in the cytomembranes and cytoplasm of neurons and astrocytes,while CXCR5 was mainly expressed in the cytomembranes and cytoplasm of neurons.CXCL13 and CXCR5 mRNA expression and protein levels were found to be significantly up-regulated in the TLE patients and TLE rats.Further,CXCL13 and CXCR5 protein levels were altered during the different epileptic phases after onset of status epilepticus(SE)in the pilocarpine model rats,including the acute phase(6,24,and 72 h),latent phase(7 and 14 d)and chronic phase(30 d and 60 d groups).Conclusion:CXCL13 and CXCR5 were up-regulated in brain tissues of intractable temporal lobe epilepsy patients and epilepsy rats.The CXCL13-CXCR5 signaling pathway may play a possible pathogenic role in IE.CXCL13 and CXCR5 may represent potential biomarkers of brain inflammation in epileptic patients.