Topiramate increases local proinflammatory cytokine gene expression after nerve crush lesion in rats exclusively in injured nerves

Abstract

Topiramate (TPM) is an anticonvulsant and putative neuroprotective drug. As some older anticonvulsants were shown to modulate cytokine expression, the authors investigated whether TPM influences injury-induced cytokine expression in the sciatic nerve and the L4/5 dorsal root ganglia (DRG) of rats. Twenty-five rats 12 and 24 hours after sciatic nerve crush lesion were investigated. Using quantitative real-time polymerase chain reaction, the gene expression of the proinflammatory cytokines tumor necrosis factor-alpha (TNF), its receptors 1 and 2 (TNFR1 and TNFR2), interleukin (IL) - 1β , and IL-6 and the gene expression of the anti-inflammatory cytokines IL-10 and transforming growth factor-beta (TGFβ) were measured. In sciatic nerves, the gene expression of all cytokines and TNFR1 and TNFR2 peaked 12 hours after surgery except for IL-6 which had its maximum at 24 hours. The TPM effect was restricted to injured nerves: TPM increased gene expression of TNF (×3), IL-6 (×2.2), and IL-1β (×1.4), whereas decreased gene expression of IL-10 (×0.7). The authors propose that TPM influences cytokine gene expression by acting on Schwann cells in the injured nerve. Keywords: Topiramate, Sciatic nerve crush, Proinflammatory cytokines, Anti-inflammatory cytokines DOI:10.5055/jndr.2013.0011