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Theme: Epilepsy - Special Report

Novel frontiers in epilepsy treatments: preventing epileptogenesis by targeting inflammation

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Pages 615-625 | Published online: 09 Jan 2014

References

  • Brodie MJ, Barry SJ, Bamagous GA, Norrie JD, Kwan P. Patterns of treatment response in newly diagnosed epilepsy. Neurology 78(20), 1548–1554 (2012).
  • Löscher W, Schmidt D. Modern antiepileptic drug development has failed to deliver: ways out of the current dilemma. Epilepsia 52(4), 657–678 (2011).
  • Herman ST. Clinical trials for prevention of epileptogenesis. Epilepsy Res. 68(1), 35–38 (2006).
  • Beghi E. Overview of studies to prevent posttraumatic epilepsy. Epilepsia 44(Suppl. 10), 21–26 (2003).
  • Temkin NR. Antiepileptogenesis and seizure prevention trials with antiepileptic drugs: meta-analysis of controlled trials. Epilepsia 42(4), 515–524 (2001).
  • Temkin NR. Preventing and treating posttraumatic seizures: the human experience. Epilepsia 50(Suppl. 2), 10–13 (2009).
  • Mani R, Pollard J, Dichter MA. Human clinical trails in antiepileptogenesis. Neurosci. Lett. 497(3), 251–256 (2011).
  • Galanopoulou AS, Buckmaster PS, Staley KJ et al.; American Epilepsy Society Basic Science Committee And The International League Against Epilepsy Working Group On Recommendations For Preclinical Epilepsy Drug Discovery. Identification of new epilepsy treatments: issues in preclinical methodology. Epilepsia 53(3), 571–582 (2012).
  • Schmidt D. Is antiepileptogenesis a realistic goal in clinical trials? Concerns and new horizons. Epileptic Disord. 14(2), 105–113 (2012).
  • Löscher W, Brandt C. Prevention or modification of epileptogenesis after brain insults: experimental approaches and translational research. Pharmacol. Rev. 62(4), 668–700 (2010).
  • Pitkänen A, Bolkvadze T, Immonen R. Anti-epileptogenesis in rodent post-traumatic epilepsy models. Neurosci. Lett. 497(3), 163–171 (2011).
  • Sloviter RS. Progress on the issue of excitotoxic injury modification vs. real neuroprotection; implications for post-traumatic epilepsy. Neuropharmacology 61(5–6), 1048–1050 (2011).
  • D’Ambrosio R, Fairbanks JP, Fender JS, Born DE, Doyle DL, Miller JW. Post-traumatic epilepsy following fluid percussion injury in the rat. Brain 127(Pt 2), 304–314 (2004).
  • D’Ambrosio R, Fender JS, Fairbanks JP et al. Progression from frontal-parietal to mesial-temporal epilepsy after fluid percussion injury in the rat. Brain 128(Pt 1), 174–188 (2005).
  • Hunt RF, Scheff SW, Smith BN. Posttraumatic epilepsy after controlled cortical impact injury in mice. Exp. Neurol. 215(2), 243–252 (2009).
  • Dubé C, Richichi C, Bender RA, Chung G, Litt B, Baram TZ. Temporal lobe epilepsy after experimental prolonged febrile seizures: prospective analysis. Brain 129(Pt 4), 911–922 (2006).
  • Oakley JC, Kalume F, Yu FH, Scheuer T, Catterall WA. Temperature- and age-dependent seizures in a mouse model of severe myoclonic epilepsy in infancy. Proc. Natl Acad. Sci. USA 106(10), 3994–3999 (2009).
  • Buckingham SC, Campbell SL, Haas BR et al. Glutamate release by primary brain tumors induces epileptic activity. Nat. Med. 17(10), 1269–1274 (2011).
  • Williams PA, Dudek FE. A chronic histopathological and electrophysiological analysis of a rodent hypoxic-ischemic brain injury model and its use as a model of epilepsy. Neuroscience 149(4), 943–961 (2007).
  • Rakhade SN, Klein PM, Huynh T et al. Development of later life spontaneous seizures in a rodent model of hypoxia-induced neonatal seizures. Epilepsia 52(4), 753–765 (2011).
  • Kelly KM, Kharlamov A, Hentosz TM et al. Photothrombotic brain infarction results in seizure activity in aging Fischer 344 and Sprague Dawley rats. Epilepsy Res. 47(3), 189–203 (2001).
  • Kharlamov EA, Jukkola PI, Schmitt KL, Kelly KM. Electrobehavioral characteristics of epileptic rats following photothrombotic brain infarction. Epilepsy Res. 56(2–3), 185–203 (2003).
  • Stewart KA, Wilcox KS, Fujinami RS, White HS. Development of postinfection epilepsy after Theiler’s virus infection of C57BL/6 mice. J. Neuropathol. Exp. Neurol. 69(12), 1210–1219 (2010).
  • Agrawal A, Timothy J, Pandit L, Manju M. Post-traumatic epilepsy: an overview. Clin. Neurol. Neurosurg. 108(5), 433–439 (2006).
  • Eftekhar B, Sahraian MA, Nouralishahi B et al. Prognostic factors in the persistence of posttraumatic epilepsy after penetrating head injuries sustained in war. J. Neurosurg. 110(2), 319–326 (2009).
  • Christensen J. Traumatic brain injury: risks of epilepsy and implications for medicolegal assessment. Epilepsia 53(Suppl. 4), 43–47 (2012).
  • Frey LC. Epidemiology of posttraumatic epilepsy: a critical review. Epilepsia 44(Suppl. 10), 11–17 (2003).
  • Eastman CL, Verley DR, Fender JS, Temkin NR, D’Ambrosio R. ECoG studies of valproate, carbamazepine and halothane in frontal-lobe epilepsy induced by head injury in the rat. Exp. Neurol. 224(2), 369–388 (2010).
  • Eastman CL, Verley DR, Fender JS et al. Antiepileptic and antiepileptogenic performance of carisbamate after head injury in the rat: blind and randomized studies. J. Pharmacol. Exp. Ther. 336(3), 779–790 (2011).
  • Thompson HJ, Lifshitz J, Marklund N et al. Lateral fluid percussion brain injury: a 15-year review and evaluation. J. Neurotrauma 22(1), 42–75 (2005).
  • D’Ambrosio R, Eastman CL, Darvas F et al. Mild passive focal cooling prevents epileptic seizures after head injury in rats. Ann. Neurol. 73(2), 199–209 (2013).
  • Curia G, Levitt M, Fender JS, Miller JW, Ojemann J, D’Ambrosio R. Impact of injury location and severity on posttraumatic epilepsy in the rat: role of frontal neocortex. Cereb. Cortex 21(7), 1574–1592 (2011).
  • Diaz-Arrastia R, Agostini MA, Madden CJ, Van Ness PC. Posttraumatic epilepsy: the endophenotypes of a human model of epileptogenesis. Epilepsia 50(Suppl. 2), 14–20 (2009).
  • Bancaud J, Talairach J. Clinical semiology of frontal lobe seizures. Adv. Neurol. 57, 3–58 (1992).
  • Williamson PD, Spencer DD, Spencer SS, Novelly RA, Mattson RH. Complex partial seizures of frontal lobe origin. Ann. Neurol. 18(4), 497–504 (1985).
  • Williamson PD, Spencer SS. Clinical and EEG features of complex partial seizures of extratemporal origin. Epilepsia 27(Suppl. 2), S46–S63 (1986).
  • Ikeda A, Hirasawa K, Kinoshita M et al. Negative motor seizure arising from the negative motor area: is it ictal apraxia? Epilepsia 50(9), 2072–2084 (2009).
  • Williamson PD, Spencer DD, Spencer SS, Novelly RA, Mattson RH. Complex partial seizures of frontal lobe origin. Ann. Neurol. 18(4), 497–504 (1985).
  • Williamson PD, Spencer SS. Clinical and EEG features of complex partial seizures of extratemporal origin. Epilepsia 27(Suppl. 2), S46–S63 (1986).
  • Fox JL, Vu EN, Doyle-Waters M, Brubacher JR, Abu-Laban R, Hu Z. Prophylactic hypothermia for traumatic brain injury: a quantitative systematic review. CJEM 12(4), 355–364 (2010).
  • Polderman KH. Induced hypothermia and fever control for prevention and treatment of neurological injuries. Lancet 371(9628), 1955–1969 (2008).
  • Jiang JY, Xu W, Li WP et al. Effect of long-term mild hypothermia or short-term mild hypothermia on outcome of patients with severe traumatic brain injury. J. Cereb. Blood Flow Metab. 26(6), 771–776 (2006).
  • Sadaka F, Veremakis C. Therapeutic hypothermia for the management of intracranial hypertension in severe traumatic brain injury: a systematic review. Brain Inj. 26(7–8), 899–908 (2012).
  • Liu WG, Qiu WS, Zhang Y, Wang WM, Lu F, Yang XF. Effects of selective brain cooling in patients with severe traumatic brain injury: a preliminary study. J. Int. Med. Res. 34(1), 58–64 (2006).
  • Qiu W, Shen H, Zhang Y et al. Noninvasive selective brain cooling by head and neck cooling is protective in severe traumatic brain injury. J. Clin. Neurosci. 13(10), 995–1000 (2006).
  • Aronica E, Crino PB. Inflammation in epilepsy: clinical observations. Epilepsia 52(Suppl. 3), 26–32 (2011).
  • Ravizza T, Balosso S, Vezzani A. Inflammation and prevention of epileptogenesis. Neurosci. Lett. 497(3), 223–230 (2011).
  • Vezzani A, French J, Bartfai T, Baram TZ. The role of inflammation in epilepsy. Nat. Rev. Neurol. 7(1), 31–40 (2011).
  • Vezzani A, Friedman A, Dingledine RJ. The role of inflammation in epileptogenesis. Neuropharmacology 69, 16–24 (2013).
  • Xue M, Del Bigio MR. Intracerebral injection of autologous whole blood in rats: time course of inflammation and cell death. Neurosci. Lett. 283(3), 230–232 (2000).
  • Katsuki H. Exploring neuroprotective drug therapies for intracerebral hemorrhage. J. Pharmacol. Sci. 114(4), 366–378 (2010).
  • Andersson U, Rauvala H. Introduction: HMGB1 in inflammation and innate immunity. J. Intern. Med. 270(4), 296–300 (2011).
  • Gao TL, Yuan XT, Yang D et al. Expression of HMGB1 and RAGE in rat and human brains after traumatic brain injury. J. Trauma Acute Care Surg. 72(3), 643–649 (2012).
  • Brown KL, Cosseau C, Gardy JL, Hancock RE. Complexities of targeting innate immunity to treat infection. Trends Immunol. 28(6), 260–266 (2007).
  • Griffiths MR, Gasque P, Neal JW. The regulation of the CNS innate immune response is vital for the restoration of tissue homeostasis (repair) after acute brain injury: a brief review. Int. J. Inflam. 2010, 151097 (2010).
  • Merrill JE, Benveniste EN. Cytokines in inflammatory brain lesions: helpful and harmful. Trends Neurosci. 19(8), 331–338 (1996).
  • Morganti-Kossmann MC, Rancan M, Stahel PF, Kossmann T. Inflammatory response in acute traumatic brain injury: a double-edged sword. Curr. Opin. Crit. Care 8(2), 101–105 (2002).
  • Serhan CN, Brain SD, Buckley CD et al. Resolution of inflammation: state of the art, definitions and terms. FASEB J. 21(2), 325–332 (2007).
  • Moseley JI, Ojemann GA, Ward AA Jr. Unit activity during focal cortical hypothermia in the normal cortex. Exp. Neurol. 37(1), 152–163 (1972).
  • Fritz HG, Bauer R. Secondary injuries in brain trauma: effects of hypothermia. J. Neurosurg. Anesthesiol. 16(1), 43–52 (2004).
  • Zhao H, Steinberg GK, Sapolsky RM. General versus specific actions of mild-moderate hypothermia in attenuating cerebral ischemic damage. J. Cereb. Blood Flow Metab. 27(12), 1879–1894 (2007).
  • Sahuquillo J, Vilalta A. Cooling the injured brain: how does moderate hypothermia influence the pathophysiology of traumatic brain injury. Curr. Pharm. Des. 13(22), 2310–2322 (2007).
  • Polderman KH. Mechanisms of action, physiological effects, and complications of hypothermia. Crit. Care Med. 37(Suppl. 7), S186–S202 (2009).
  • Dietrich WD, Atkins CM, Bramlett HM. Protection in animal models of brain and spinal cord injury with mild to moderate hypothermia. J. Neurotrauma 26(3), 301–312 (2009).
  • Dietrich WD, Bramlett HM. The evidence for hypothermia as a neuroprotectant in traumatic brain injury. Neurotherapeutics 7(1), 43–50 (2010).
  • Ravizza T, Balosso S, Vezzani A. Inflammation and prevention of epileptogenesis. Neurosci. Lett. 497(3), 223–230 (2011).
  • Librizzi L, Noè F, Vezzani A, de Curtis M, Ravizza T. Seizure-induced brain-borne inflammation sustains seizure recurrence and blood–brain barrier damage. Ann. Neurol. 72(1), 82–90 (2012).
  • Bartfai T, Sanchez-Alavez M, Andell-Jonsson S et al. Interleukin-1 system in CNS stress: seizures, fever, and neurotrauma. Ann. NY Acad. Sci. 1113, 173–177 (2007).
  • Cederberg D, Siesjö P. What has inflammation to do with traumatic brain injury? Childs. Nerv. Syst. 26(2), 221–226 (2010).
  • Devinsky O, Vezzani A, Najjar S, De Lanerolle NC, Rogawski MA. Glia and epilepsy: excitability and inflammation. Trends Neurosci. 36(3), 174–184 (2013).
  • Folkersma H, Boellaard R, Yaqub M et al. Widespread and prolonged increase in (R)-(11)C-PK11195 binding after traumatic brain injury. J. Nucl. Med. 52(8), 1235–1239 (2011).
  • Ramlackhansingh AF, Brooks DJ, Greenwood RJ et al. Inflammation after trauma: microglial activation and traumatic brain injury. Ann. Neurol. 70(3), 374–383 (2011).
  • Cavalli A, Bolognesi ML, Minarini A et al. Multi-target-directed ligands to combat neurodegenerative diseases. J. Med. Chem. 51(3), 347–372 (2008).
  • Mencher SK, Wang LG. Promiscuous drugs compared to selective drugs (promiscuity can be a virtue). BMC Clin. Pharmacol. 5(1), 3 (2005).
  • Margulies S, Hicks R; Combination therapies for traumatic brain injury workshop leaders. Combination therapies for traumatic brain injury: prospective considerations. J. Neurotrauma 26(6), 925–939 (2009).
  • Vink R, Nimmo AJ. Multifunctional drugs for head injury. Neurotherapeutics 6(1), 28–42 (2009).
  • Lampl Y, Boaz M, Gilad R et al. Minocycline treatment in acute stroke: an open-label, evaluator-blinded study. Neurology 69(14), 1404–1410 (2007).
  • Stein DG. Is progesterone a worthy candidate as a novel therapy for traumatic brain injury? Dialogues Clin. Neurosci. 13(3), 352–359 (2011).
  • Ma J, Huang S, Qin S, You C. Progesterone for acute traumatic brain injury. Cochrane Database Syst. Rev. 10, CD008409 (2012).
  • Yong VW, Wells J, Giuliani F, Casha S, Power C, Metz LM. The promise of minocycline in neurology. Lancet Neurol. 3(12), 744–751 (2004).
  • Jordan J, Fernandez-Gomez FJ, Ramos M, Ikuta I, Aguirre N, Galindo MF. Minocycline and cytoprotection: shedding new light on a shadowy controversy. Curr. Drug Deliv. 4(3), 225–231 (2007).
  • Sanchez Mejia RO, Ona VO, Li M, Friedlander RM. Minocycline reduces traumatic brain injury-mediated caspase-1 activation, tissue damage, and neurological dysfunction. Neurosurgery 48(6), 1393–1399; discussion 1399 (2001).
  • Siopi E, Llufriu-Dabén G, Fanucchi F, Plotkine M, Marchand-Leroux C, Jafarian-Tehrani M. Evaluation of late cognitive impairment and anxiety states following traumatic brain injury in mice: the effect of minocycline. Neurosci. Lett. 511(2), 110–115 (2012).
  • Wang DD, Englot DJ, Garcia PA, Lawton MT, Young WL. Minocycline- and tetracycline-class antibiotics are protective against partial seizures in vivo. Epilepsy Behav. 24(3), 314–318 (2012).
  • Heo K, Cho YJ, Cho KJ et al. Minocycline inhibits caspase-dependent and -independent cell death pathways and is neuroprotective against hippocampal damage after treatment with kainic acid in mice. Neurosci. Lett. 398(3), 195–200 (2006).
  • Lu DC, Zador Z, Yao J, Fazlollahi F, Manley GT. Aquaporin-4 reduces post-traumatic seizure susceptibility by promoting astrocytic glial scar formation in mice. J. Neurotrauma doi:10.1089/neu.2011.2114 (2011) (Epub ahead of print).
  • Abraham J, Fox PD, Condello C, Bartolini A, Koh S. Minocycline attenuates microglia activation and blocks the long-term epileptogenic effects of early-life seizures. Neurobiol. Dis. 46(2), 425–430 (2012).
  • Nowak M, Strzelczyk A, Reif PS et al. Minocycline as potent anticonvulsant in a patient with astrocytoma and drug resistant epilepsy. Seizure 21(3), 227–228 (2012).
  • Hua F, Wang J, Ishrat T et al. Genomic profile of Toll-like receptor pathways in traumatically brain-injured mice: effect of exogenous progesterone. J. Neuroinflammation 8, 42 (2011).
  • Jiang C, Wang J, Li X, Liu C, Chen N, Hao Y. Progesterone exerts neuroprotective effects by inhibiting inflammatory response after stroke. Inflamm. Res. 58(9), 619–624 (2009).
  • Luoma JI, Kelley BG, Mermelstein PG. Progesterone inhibition of voltage-gated calcium channels is a potential neuroprotective mechanism against excitotoxicity. Steroids 76(9), 845–855 (2011).
  • Siopi E, Cho AH, Homsi S et al. Progesterone in the treatment of acute traumatic brain injury: a clinical perspective and update. Neuroscience. 191, 101–106 (2011).
  • Stein DG, Sayeed I. Is progesterone worth consideration as a treatment for brain injury? AJR. Am. J. Roentgenol. 194(1), 20–22 (2010).
  • Espinoza TR, Wright DW. The role of progesterone in traumatic brain injury. J. Head Trauma Rehabil. 26(6), 497–499 (2011).
  • Singh M, Su C. Progesterone, brain-derived neurotrophic factor and neuroprotection. Neuroscience 239, 84–91 (2012).
  • Gibson CL, Gray LJ, Bath PM, Murphy SP. Progesterone for the treatment of experimental brain injury; a systematic review. Brain 131(Pt 2), 318–328 (2008).
  • Sayeed I, Stein DG. Progesterone as a neuroprotective factor in traumatic and ischemic brain injury. Prog. Brain Res. 175, 219–237 (2009).
  • Wright DW, Kellermann AL, Hertzberg VS et al. ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury. Ann. Emerg. Med. 49(4), 391–402, 402.e1 (2007).
  • Xiao G, Wei J, Yan W, Wang W, Lu Z. Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial. Crit. Care 12(2), R61 (2008).
  • Raymont V, Salazar AM, Lipsky R, Goldman D, Tasick G, Grafman J. Correlates of posttraumatic epilepsy 35 years following combat brain injury. Neurology 75(3), 224–229 (2010).
  • Annegers JF, Hauser WA, Coan SP, Rocca WA. A population-based study of seizures after traumatic brain injuries. N. Engl. J. Med. 338(1), 20–24 (1998).
  • Ryvlin P, Montavont A, Nighoghossian N. Optimizing therapy of seizures in stroke patients. Neurology 67(12 Suppl. 4), S3–S9 (2006).
  • Jennett B. Outcome after severe head injury: definitions and predictions. Med. J. Aust. 2(13), 475–477 (1976).
  • Temkin NR. Risk factors for posttraumatic seizures in adults. Epilepsia 44(Suppl. 10), 18–20 (2003).
  • D’Ambrosio R, Hakimian S, Stewart T et al. Functional definition of seizure provides new insight into post-traumatic epileptogenesis. Brain 132(Pt 10), 2805–2821 (2009).
  • Stead M, Bower M, Brinkmann BH et al. Microseizures and the spatiotemporal scales of human partial epilepsy. Brain 133(9), 2789–2797 (2010).
  • Devinsky O, Kelley K, Porter RJ, Theodore WH. Clinical and electroencephalographic features of simple partial seizures. Neurology 38(9), 1347–1352 (1988).
  • Devinsky O, Sato S, Kufta CV et al. Electroencephalographic studies of simple partial seizures with subdural electrode recordings. Neurology 39(4), 527–533 (1989).
  • Hoppe C, Poepel A, Elger CE. Epilepsy: accuracy of patient seizure counts. Arch. Neurol. 64(11), 1595–1599 (2007).
  • Doelken MT, Stefan H, Pauli E et al. (1) H-MRS profile in MRI positive- versus MRI negative patients with temporal lobe epilepsy. Seizure 17(6), 490–497 (2008).
  • Holmes MD, Tucker DM, Quiring JM, Hakimian S, Miller JW, Ojemann JG. Comparing noninvasive dense array and intracranial electroencephalography for localization of seizures. Neurosurgery 66(2), 354–362 (2010).
  • Pitkänen A, Lukasiuk K. Molecular biomarkers of epileptogenesis. Biomark. Med. 5(5), 629–633 (2011).
  • Holtman L, van Vliet EA, Aronica E, Wouters D, Wadman WJ, Gorter JA. Blood plasma inflammation markers during epileptogenesis in post-status epilepticus rat model for temporal lobe epilepsy. Epilepsia 54(4), 589–595 (2013).
  • Klitgaard H, Löscher W, Twyman RE, Schmidt D. New avenues for antiepileptic drug discovery and development: a joint endeavor of academia and industry. Nature Rev. Drug Discovery (2013) (In Press).
  • Chan A, Pirmohamed M, Comabella M. Pharmacogenomics in neurology: current state and future steps. Ann. Neurol. 70(5), 684–697 (2011).
  • Gomes WA, Shinnar S. Prospects for imaging-related biomarkers of human epileptogenesis: a critical review. Biomark. Med. 5(5), 599–606 (2011).
  • Staba RJ, Bragin A. High-frequency oscillations and other electrophysiological biomarkers of epilepsy: underlying mechanisms. Biomark. Med. 5(5), 545–556 (2011).
  • Blumenfeld H, Klein JP, Schridde U et al. Early treatment suppresses the development of spike-wave epilepsy in a rat model. Epilepsia 49(3), 400–409 (2008).
  • Dezsi G, Ozturk E, Stanic D et al. Ethosuximide reduces epileptogenesis and behavioral comorbidity in the GAERS model of genetic generalized epilepsy. Epilepsia 54(4), 635–643 (2013).
  • Russo E, Citraro R, Scicchitano F et al. Comparison of the antiepileptogenic effects of an early long-term treatment with ethosuximide or levetiracetam in a genetic animal model of absence epilepsy. Epilepsia 51(8), 1560–1569 (2010).
  • Russo E, Citraro R, Donato G et al. mTOR inhibition modulates epileptogenesis, seizures and depressive behavior in a genetic rat model of absence epilepsy. Neuropharmacology 69, 25–36 (2013).
  • Galanopoulou AS, Gorter JA, Cepeda C. Finding a better drug for epilepsy: the mTOR pathway as an antiepileptogenic target. Epilepsia 53(7), 1119–1130 (2012).
  • Perucca E, Tomson T. The pharmacological treatment of epilepsy in adults. Lancet Neurol. 10(5), 446–456 (2011).
  • Perucca E, French J, Bialer M. Development of new antiepileptic drugs: challenges, incentives, and recent advances. Lancet Neurol. 6(9), 793–804 (2007).
  • Bialer M, Johannessen SI, Levy RH, Perucca E, Tomson T, White HS. Progress report on new antiepileptic drugs: a summary of the Eleventh Eilat Conference (EILAT XI). Epilepsy Res. 103(1), 2–30 (2013).
  • Paul SM, Mytelka DS, Dunwiddie CT et al. How to improve R&D productivity: the pharmaceutical industry’s grand challenge. Nat. Rev. Drug Discov. 9(3), 203–214 (2010).
  • Perucca E. What clinical trial designs have been used to test antiepileptic drugs and do we need to change them? Epileptic Disord. 14(2), 124–131 (2012).
  • Friedman D, French JA. Clinical trials for therapeutic assessment of antiepileptic drugs in the 21st century: obstacles and solutions. Lancet Neurol. 11(9), 827–834 (2012).
  • Ajmone-Cat MA, Bernardo A, Greco A, Minghetti L. Non-steroidal anti-inflammatory drugs and brain inflammation: effects on microglial functions. Pharmaceuticals 3(6), 1949–1965 (2010).
  • Ma L, Cui XL, Wang Y et al. Aspirin attenuates spontaneous recurrent seizures and inhibits hippocampal neuronal loss, mossy fiber sprouting and aberrant neurogenesis following pilocarpine-induced status epilepticus in rats. Brain Res. 1469, 103–113 (2012).
  • Gaur V, Kumar A. Effect of nonselective and selective COX-2 inhibitors on memory dysfunction, glutathione system, and tumor necrosis factor alpha level against cerebral ischemia reperfusion injury. Drug Chem. Toxicol. 35(2), 218–224 (2012).
  • Jung KH, Chu K, Lee ST et al. Cyclooxygenase-2 inhibitor, celecoxib, inhibits the altered hippocampal neurogenesis with attenuation of spontaneous recurrent seizures following pilocarpine-induced status epilepticus. Neurobiol. Dis. 23(2), 237–246 (2006).
  • Chao PK, Lu KT, Jhu JY et al. Indomethacin protects rats from neuronal damage induced by traumatic brain injury and suppresses hippocampal IL-1b release through the inhibition of Nogo-A expression. J. Neuroinflammation 9, 121 (2012).
  • Girgis H, Palmier B, Croci N, Soustrat M, Plotkine M, Marchand-Leroux C. Effects of selective and non-selective cyclooxygenase inhibition against neurological deficit and brain oedema following closed head injury in mice. Brain Res. 1491, 78–87 (2013).
  • Dhir A, Naidu PS, Kulkarni SK. Neuroprotective effect of nimesulide, a preferential COX-2 inhibitor, against pentylenetetrazol (PTZ)-induced chemical kindling and associated biochemical parameters in mice. Seizure 16(8), 691–697 (2007).
  • Candelario-Jalil E. Nimesulide as a promising neuroprotectant in brain ischemia: new experimental evidences. Pharmacol. Res. 57(4), 266–273 (2008).
  • Polascheck N, Bankstahl M, Löscher W. The COX-2 inhibitor parecoxib is neuroprotective but not antiepileptogenic in the pilocarpine model of temporal lobe epilepsy. Exp. Neurol. 224(1), 219–233 (2010).
  • Wang Q, Yan J, Chen X et al. Statins: multiple neuroprotective mechanisms in neurodegenerative diseases. Exp. Neurol. 230(1), 27–34 (2011).
  • Wible EF, Laskowitz DT. Statins in traumatic brain injury. Neurotherapeutics 7(1), 62–73 (2010).
  • Lu D, Goussev A, Chen J et al. Atorvastatin reduces neurological deficit and increases synaptogenesis, angiogenesis, and neuronal survival in rats subjected to traumatic brain injury. J. Neurotrauma 21(1), 21–32 (2004).
  • Chauhan NB, Gatto R. Restoration of cognitive deficits after statin feeding in TBI. Restor. Neurol. Neurosci. 29(1), 23–34 (2011).
  • Indraswari F, Wang H, Lei B et al. Statins improve outcome in murine models of intracranial hemorrhage and traumatic brain injury: a translational approach. J. Neurotrauma 29(7), 1388–1400 (2012).
  • Mahmood A, Goussev A, Kazmi H, Qu C, Lu D, Chopp M. Long-term benefits after treatment of traumatic brain injury with simvastatin in rats. Neurosurgery 65(1), 187–191; discussion 191 (2009).
  • Xie C, Sun J, Qiao W et al. Administration of simvastatin after kainic acid-induced status epilepticus restrains chronic temporal lobe epilepsy. PLoS ONE 6(9), e24966 (2011).
  • Fleischmann R, Stern R, Iqbal I. Anakinra: an inhibitor of IL-1 for the treatment of rheumatoid arthritis. Expert Opin. Biol. Ther. 4(8), 1333–1344 (2004).
  • Pradillo JM, Denes A, Greenhalgh AD et al. Delayed administration of interleukin-1 receptor antagonist reduces ischemic brain damage and inflammation in comorbid rats. J. Cereb. Blood Flow Metab. 32(9), 1810–1819 (2012).
  • Arcasoy MO. The non-haematopoietic biological effects of erythropoietin. Br. J. Haematol. 141(1), 14–31 (2008).
  • Jung KH, Chu K, Lee ST et al. Molecular alterations underlying epileptogenesis after prolonged febrile seizure and modulation by erythropoietin. Epilepsia 52(3), 541–550 (2011).
  • Chu K, Jung KH, Lee ST et al. Erythropoietin reduces epileptogenic processes following status epilepticus. Epilepsia 49(10), 1723–1732 (2008).
  • Rabie T, Marti HH. Brain protection by erythropoietin: a manifold task. Physiology (Bethesda) 23, 263–274 (2008).
  • Stirling DP, Koochesfahani KM, Steeves JD, Tetzlaff W. Minocycline as a neuroprotective agent. Neuroscientist 11(4), 308–322 (2005).
  • Kovesdi E, Kamnaksh A, Wingo D et al. Acute minocycline treatment mitigates the symptoms of mild blast-induced traumatic brain injury. Front. Neurol. 3, 111 (2012).
  • Tintinger GR, Feldman C, Theron AJ, Anderson R. Montelukast: more than a cysteinyl leukotriene receptor antagonist? Scientific World J. 10, 2403–2413 (2010).
  • Zhao R, Shi WZ, Zhang YM, Fang SH, Wei EQ. Montelukast, a cysteinyl leukotriene receptor-1 antagonist, attenuates chronic brain injury after focal cerebral ischaemia in mice and rats. J. Pharm. Pharmacol. 63(4), 550–557 (2011).
  • Brinton RD, Thompson RF, Foy MR et al. Progesterone receptors: form and function in brain. Front. Neuroendocrinol. 29(2), 313–339 (2008).
  • Weichhart T, Costantino G, Poglitsch M et al. The TSC-mTOR signaling pathway regulates the innate inflammatory response. Immunity 29(4), 565–577 (2008).
  • Hartford CM, Ratain MJ. Rapamycin: something old, something new, sometimes borrowed and now renewed. Clin. Pharmacol. Ther. 82(4), 381–388 (2007).
  • Erlich S, Alexandrovich A, Shohami E, Pinkas-Kramarski R. Rapamycin is a neuroprotective treatment for traumatic brain injury. Neurobiol. Dis. 26(1), 86–93 (2007).
  • Park J, Zhang J, Qiu J et al. Combination therapy targeting Akt and mammalian target of rapamycin improves functional outcome after controlled cortical impact in mice. J. Cereb. Blood Flow Metab. 32(2), 330–340 (2012).
  • Sunnen CN, Brewster AL, Lugo JN et al. Inhibition of the mammalian target of rapamycin blocks epilepsy progression in NS-Pten conditional knockout mice. Epilepsia 52(11), 2065–2075 (2011).
  • Russo E, Citraro R, Constanti A, De Sarro G. The mTOR signaling pathway in the brain: focus on epilepsy and epileptogenesis. Mol. Neurobiol. 46(3), 662–681 (2012).
  • Sliwa A, Plucinska G, Bednarczyk J, Lukasiuk K. Post-treatment with rapamycin does not prevent epileptogenesis in the amygdala stimulation model of temporal lobe epilepsy. Neurosci. Lett. 509(2), 105–109 (2012).
  • Kumar V, Chhibber S. Thalidomide: an old drug with new action. J. Chemother. 23(6), 326–334 (2011).
  • Zhang L, Qu Y, Tang J et al. PI3K/Akt signaling pathway is required for neuroprotection of thalidomide on hypoxic-ischemic cortical neurons in vitro. Brain Res. 1357, 157–165 (2010).
  • Hyakkoku K, Nakajima Y, Izuta H et al. Thalidomide protects against ischemic neuronal damage induced by focal cerebral ischemia in mice. Neuroscience 159(2), 760–769 (2009).

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