Topiramate increases local proinflammatory cytokine gene expression after nerve crush lesion in rats exclusively in injured nerves
DOI:
https://doi.org/10.5055/jndr.2013.0011Abstract
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
References
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.
