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

Nurcan Üçeyler, MD, Stefan Bischofs, MD, Claudia Sommer, MD

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)-, 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


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Angehagen M, Ben-Menachem E, Shank R, et al.: Topiramate modulation of kainate-induced calcium currents is inversely related to channel phosphorylation level. J Neurochem. 2004; 88: 320-325.

Angehagen M, Ronnback L, Hansson E, et al.: Topiramate reduces AMPA-induced Ca(2+) transients and inhibits GluR1 subunit phosphorylation in astrocytes from primary cultures. J Neurochem. 2005; 94: 1124-1130.

McLean MJ, Bukhari AA, Wamil AW: Effects of topiramate on sodium-dependent action-potential firing by mouse spinal cord neurons in cell culture. Epilepsia. 2000; 41 Suppl 1: S21-S24.

Shank RP, Gardocki JF, Streeter AJ, et al.: An overview of the preclinical aspects of topiramate: Pharmacology, pharmacokinetics, and mechanism of action. Epilepsia. 2000; 41 Suppl 1: S3-S9.

White HS, Brown SD, Woodhead JH, et al.: Topiramate modulates GABA-evoked currents in murine cortical neurons by a nonbenzodiazepine mechanism. Epilepsia. 2000; 41 Suppl 1: S17-S20.

Zhang X, Velumian AA, Jones OT, et al.: Modulation of highvoltage-activated calcium channels in dentate granule cells by topiramate. Epilepsia. 2000; 41 Suppl 1: S52-S60.

Brandes JL, Saper JR, Diamond M, et al.: Topiramate for migraine prevention: A randomized controlled trial. JAMA. 2004; 291: 965-973.

Diener HC, Tfelt-Hansen P, Dahlof C, et al.: Topiramate in migraine prophylaxis–Results from a placebo-controlled trial with propranolol as an active control. J Neurol. 2004; 251: 943-950.

Follett PL, Deng W, Dai W, et al.: Glutamate receptor-mediated oligodendrocyte toxicity in periventricular leukomalacia: A protective role for topiramate. J Neurosci. 2004; 24: 4412-4420.

Kaminski RM, Banerjee M, Rogawski MA: Topiramate selectively protects against seizures induced by ATPA, a GluR5 kainate receptor agonist. Neuropharmacology. 2004; 46: 1097-1104.

Koh S, Tibayan FD, Simpson JN, et al.: NBQX or topiramate treatment after perinatal hypoxia-induced seizures prevents later increases in seizure-induced neuronal injury. Epilepsia. 2004; 45: 569-575.

Kudin AP, Debska-Vielhaber G, Vielhaber S, et al.: The mechanism of neuroprotection by topiramate in an animal model of epilepsy. Epilepsia. 2004; 45: 1478-1487.

Kurul SH, Yis U, Kumral A, et al.: Protective effects of topiramate against hyperoxic brain injury in the developing brain. Neuropediatrics. 2009; 40: 22-27.

Liu C, Lin N, Wu B, et al.: Neuroprotective effect of memantine combined with topiramate in hypoxic-ischemic brain injury. Brain Res. 2009; 1282: 173-182.

Smith-Swintosky VL, Zhao B, Shank RP, et al.: Topiramate promotes neurite outgrowth and recovery of function after nerve injury. Neuroreport. 2001; 12: 1031-1034.

Shadiack A, Molino L, Yagel S, et al.: The novel anticonvulsant topiramate is antiallodynic in a rat model of neuropathic pain. Analgesia. 1999; 4: 173-179.

Üçeyler N, Tscharke A, Sommer C: Early cytokine expression in mouse sciatic nerve after chronic constriction nerve injury depends on calpain. Brain Behav Immun. 2007; 21(5): 553-560.

Kleinschnitz C, Brinkhoff J, Zelenka M, et al.: The extent of cytokine induction in peripheral nerve lesions depends on the mode of injury and NMDA receptor signaling. J Neuroimmunol. 2004; 149: 77-83.

Stoll G, Jander S, Schroeter M: Detrimental and beneficial effects of injury-induced inflammation and cytokine expression in the nervous system. Adv Exp Med Biol. 2002; 513: 87-113.

Makwana M, Raivich G: Molecular mechanisms in successful peripheral regeneration. FEBS J. 2005; 272: 2628-2638.

Carlson NG, Wieggel WA, Chen J, et al.: Inflammatory cytokines IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha impart neuroprotection to an excitotoxin through distinct pathways. J Immunol. 1999; 163: 3963-3968.

Venters HD, Dantzer R, Kelley KW: Tumor necrosis factoralpha induces neuronal death by silencing survival signals generated by the type I insulin-like growth factor receptor. Ann N Y Acad Sci. 2000; 917: 210-220.

Thacker MA, Clark AK, Marchand F, et al.: Pathophysiology of peripheral neuropathic pain: Immune cells and molecules. Anesth Analg. 2007; 105: 838-847.

Üçeyler N, Sommer C: Cytokine regulation in animal models of neuropathic pain and in human diseases. Neurosci Lett. 2008; 437(3): 194-198.

Ichiyama T, Okada K, Lipton JM, et al.: Sodium valproate inhibits production of TNF-alpha and IL-6 and activation of NFkappaB. Brain Res. 2000; 857: 246-251.

Verrotti A, Basciani F, Trotta D, et al.: Effect of anticonvulsant drugs on interleukins-1, -2 and -6 and monocyte chemoattractant protein-1. Clin Exp Med. 2001; 1: 133-136.

Pacifici R, Zuccaro P, Iannetti P, et al.: Immunologic aspects of vigabatrin treatment in epileptic children. Epilepsia. 1995; 36: 423-426.

Sills GJ, Butler E, Forrest G, et al.: Vigabatrin, but not gabapentin or topiramate, produces concentration-related effects on enzymes and intermediates of the GABA shunt in rat brain and retina. Epilepsia. 2003; 44: 886-892.

De Koning P, Brakkee JH, Gispen WH: Methods for producing a reproducible crush in the sciatic and tibial nerve of the rat and rapid and precise testing of return of sensory function. Beneficial effects of melanocortins. J Neurol Sci. 1986; 74: 237-246.

George A, Buehl A, Sommer C: Wallerian degeneration after crush injury of rat sciatic nerve increases endo- and epineurial tumor necrosis factor-alpha protein. Neurosci Lett. 2004; 372: 215- 219.

Taskinen HS, Ruohonen S, Jagodic M, et al.: Distinct expression of TGF-β1 mRNA in the endo- and epineurium after nerve injury. J Neurotrauma. 2004; 21(7): 969-975.

Yang FL, Li CH, Hsu BG, et al.: The reduction of tumor necrosis factor-alpha release and tissue damage by pentobarbital in the experimental endotoxemia model. Shock. 2007; 28: 309-316.

Deutsch SI, Schwartz BL, Rosse RB, et al.: Adjuvant topiramate administration: A pharmacologic strategy for addressing NMDA receptor hypofunction in schizophrenia. Clin Neuropharmacol. 2003; 26: 199-206.

Bischofs S, Zelenka M, Sommer C: Evaluation of topiramate as an anti-hyperalgesic and neuroprotective agent in the peripheral nervous system. J Peripher Nerv Syst. 2004; 9: 70-78.

Üçeyler N, Eberle T, Rolke R, et al.: Differential expression patterns of cytokines in complex regional pain syndrome. Pain. 2007; 132: 195-205.

Üçeyler N, Rogausch JP, Toyka KV, et al.: Differential expression of cytokines in painful and painless neuropathies. Neurology. 2007; 69: 42-49.

Backonja MM, Coe CL, Muller DA, et al.: Altered cytokine levels in the blood and cerebrospinal fluid of chronic pain patients. J Neuroimmunol. 2008; 195: 157-163.




DOI: https://doi.org/10.5055/jndr.2013.0011

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