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Current Molecular Pharmacology


ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

Review Article

Therapeutic Targets for the Treatment of Comorbidities Associated with Epilepsy

Author(s): Kinjal Gangar and Lokesh Kumar Bhatt*

Volume 13, Issue 2, 2020

Page: [85 - 93] Pages: 9

DOI: 10.2174/1874467212666191203101606

Price: $65


One of the most common neurological disorders, which occurs among 1% of the population worldwide, is epilepsy. Therapeutic failure is common with epilepsy and nearly about 30% of patients fall in this category. Seizure suppression should not be the only goal while treating epilepsy but associated comorbidities, which can further worsen the condition, should also be considered. Treatment of such comorbidities such as depression, anxiety, cognition, attention deficit hyperactivity disorder and, various other disorders which co-exist with epilepsy or are caused due to epilepsy should also be treated. Novel targets or the existing targets are needed to be explored for the dual mechanism which can suppress both the disease and the comorbidity. New therapeutic targets such as IDO, nNOS, PAR1, NF-κb are being explored for their role in epilepsy and various comorbidities. This review explores recent therapeutic targets for the treatment of comorbidities associated with epilepsy.

Keywords: Epilepsy, comorbidities, therapeutic targets, depression, anxiety, cognition.

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Coan, A.C.; Cendes, F. Epilepsy as progressive disorders: what is the evidence that can guide our clinical decisions and how can neuroimaging help? Epilepsy Behav., 2013, 26(3), 313-321.
[] [PMID: 23127969]
Epilepsy n.d. epilepsy [April 15, 2019];
Oztas, B.; Sahin, D.; Kir, H.; Eraldemir, F.C.; Musul, M.; Kuskay, S.; Ates, N. The effect of leptin, ghrelin, and neuropeptide-Y on serum Tnf-Α, Il-1β, Il-6, Fgf-2, galanin levels and oxidative stress in an experimental generalized convulsive seizure model. Neuropeptides, 2017, 61, 31-37.
[] [PMID: 27522536]
Witkin, J.M.; Smith, J.L.; Ping, X.; Gleason, S.D.; Poe, M.M.; Li, G.; Jin, X.; Hobbs, J.; Schkeryantz, J.M.; McDermott, J.S.; Alatorre, A.I.; Siemian, J.N.; Cramer, J.W.; Airey, D.C.; Methuku, K.R.; Tiruveedhula, V.V.N.P.B.; Jones, T.M.; Crawford, J.; Krambis, M.J.; Fisher, J.L.; Cook, J.M.; Cerne, R. Bioisosteres of ethyl 8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazo [1,5-a][1,4]diazepine-3-carboxylate (HZ-166) as novel alpha 2,3 selective potentiators of GABAA receptors: Improved bioavailability enhances anticonvulsant efficacy. Neuropharmacology, 2018, 137, 332-343.
[] [PMID: 29778948]
Mwangala, P.N.; Kariuki, S.M.; Nyongesa, M.K.; Mwangi, P.; Chongwo, E.; Newton, C.R.; Abubakar, A. Cognition, mood and quality-of-life outcomes among low literacy adults living with epilepsy in rural Kenya: A preliminary study. Epilepsy Behav., 2018, 85, 45-51.
[] [PMID: 29908383]
Jones, N.C.; Salzberg, M.R.; Kumar, G.; Couper, A.; Morris, M.J.; O’Brien, T.J. Elevated anxiety and depressive-like behavior in a rat model of genetic generalized epilepsy suggesting common causation. Exp. Neurol., 2008, 209(1), 254-260.
[] [PMID: 18022621]
Elger, C.E.; Johnston, S.A.; Hoppe, C. Diagnosing and treating depression in epilepsy. Seizure, 2017, 44, 184-193.
[] [PMID: 27836391]
Fiest, K.M.; Patten, S.B.; Altura, K.C.; Bulloch, A.G.M.; Maxwell, C.J.; Wiebe, S.; Macrodimitris, S.; Jetté, N. Patterns and frequency of the treatment of depression in persons with epilepsy. Epilepsy Behav., 2014, 39, 59-64.
[] [PMID: 25203325]
Ettinger, A.B.; Weisbrot, D.M.; Nolan, E.E.; Gadow, K.D.; Vitale, S.A.; Andriola, M.R.; Lenn, N.J.; Novak, G.P.; Hermann, B.P. Symptoms of depression and anxiety in pediatric epilepsy patients. Epilepsia, 1998, 39(6), 595-599.
[] [PMID: 9637601]
Kondziella, D.; Asztely, F. Don’t be afraid to treat depression in patients with epilepsy! Acta Neurol. Scand., 2009, 119(2), 75-80.
[] [PMID: 18759799]
Błaszczyk, B.; Czuczwar, S.J. Epilepsy coexisting with depression. Pharmacol. Rep., 2016, 68(5), 1084-1092.
[] [PMID: 27634589]
Kanner, A.M. Management of psychiatric and neurological comorbidities in epilepsy. Nat. Rev. Neurol., 2016, 12(2), 106-116.
[] [PMID: 26782334]
Cardamone, L.; Salzberg, M.R.; O’Brien, T.J.; Jones, N.C. Antidepressant therapy in epilepsy: can treating the comorbidities affect the underlying disorder? Br. J. Pharmacol., 2013, 168(7), 1531-1554.
[] [PMID: 23146067]
Singh, T.; Goel, R.K. Adjuvant indoleamine 2,3-dioxygenase enzyme inhibition for comprehensive management of epilepsy and comorbid depression. Eur. J. Pharmacol., 2016, 784, 111-120.
[] [PMID: 27189423]
McKean, J.; Watts, H.; Mokszycki, R. Breakthrough seizures after starting vilazodone for depression. Pharmacotherapy, 2015, 35(3), e6-e8.
[] [PMID: 25809181]
Mazarati, A.; Siddarth, P.; Baldwin, R.A.; Shin, D.; Caplan, R.; Sankar, R. Depression after status epilepticus: behavioural and biochemical deficits and effects of fluoxetine. Brain, 2008, 131(Pt 8), 2071-2083.
[] [PMID: 18559371]
Klein, S.; Bankstahl, J.P.; Löscher, W.; Bankstahl, M. Sucrose consumption test reveals pharmacoresistant depression-associated behavior in two mouse models of temporal lobe epilepsy. Exp. Neurol., 2015, 263, 263-271.
[] [PMID: 25220610]
Najfeld, V.; Menninger, J.; Muhleman, D.; Comings, D.E.; Gupta, S.L. Localization of indoleamine 2,3-dioxygenase gene (INDO) to chromosome 8p12-->p11 by fluorescent in situ hybridization. Cytogenet. Cell Genet., 1993, 64(3-4), 231-232.
[] [PMID: 8404046]
Heitger, A. Regulation of expression and function of IDO in human dendritic cells. Curr. Med. Chem., 2011, 18(15), 2222-2233.
[] [PMID: 21517757]
Ball, H.J.; Sanchez-Perez, A.; Weiser, S.; Austin, C.J.D.; Astelbauer, F.; Miu, J.; McQuillan, J.A.; Stocker, R.; Jermiin, L.S.; Hunt, N.H. Characterization of an indoleamine 2,3-dioxygenase-like protein found in humans and mice. Gene, 2007, 396(1), 203-213.
[] [PMID: 17499941]
Xie, W.; Cai, L.; Yu, Y.; Gao, L.; Xiao, L.; He, Q.; Ren, Z.; Liu, Y. Activation of brain indoleamine 2,3-dioxygenase contributes to epilepsy-associated depressive-like behavior in rats with chronic temporal lobe epilepsy. J. Neuroinflammation, 2014, 11, 41.
[] [PMID: 24594021]
Singh, T.; Kaur, T.; Goel, R.K. Adjuvant quercetin therapy for combined treatment of epilepsy and comorbid depression. Neurochem. Int., 2017, 104, 27-33.
[] [PMID: 28065794]
Bredt, D.S. Endogenous nitric oxide synthesis: biological functions and pathophysiology. Free Radic. Res., 1999, 31(6), 577-596.
[] [PMID: 10630682]
Danjo, S.; Ishihara, Y.; Watanabe, M.; Nakamura, Y.; Itoh, K. Pentylentetrazole-induced loss of blood-brain barrier integrity involves excess nitric oxide generation by neuronal nitric oxide synthase. Brain Res., 2013, 1530, 44-53.
[] [PMID: 23831997]
Zhu, X.; Dong, J.; Shen, K.; Bai, Y.; Chao, J.; Yao, H. Neuronal nitric oxide synthase contributes to pentylenetetrazole-kindling-induced hippocampal neurogenesis. Brain Res. Bull., 2016, 121, 138-147.
[] [PMID: 26820711]
Singh, T.; Goel, R.K. Adjuvant neuronal nitric oxide synthase inhibition for combined treatment of epilepsy and comorbid depression. Pharmacol. Rep., 2017, 69(1), 143-149.
[] [PMID: 27923157]
Otsuka, S.; Ohkido, T.; Itakura, M.; Watanabe, S.; Yamamori, S.; Iida, Y.; Saito, M.; Miyaoka, H.; Takahashi, M. Dual mechanisms of rapid expression of anxiety-related behavior in pilocarpine-treated epileptic mice. Epilepsy Res., 2016, 123, 55-67.
[] [PMID: 27132018]
Rai, D.; Kerr, M.P.; McManus, S.; Jordanova, V.; Lewis, G.; Brugha, T.S. Epilepsy and psychiatric comorbidity: a nationally representative population-based study. Epilepsia, 2012, 53(6), 1095-1103.
[] [PMID: 22578079]
Fisher, P.L.; Noble, A.J. Anxiety and depression in people with epilepsy: The contribution of metacognitive beliefs. Seizure, 2017, 50, 153-159.
[] [PMID: 28667910]
Beyenburg, S.; Mitchell, A.J.; Schmidt, D.; Elger, C.E.; Reuber, M. Anxiety in patients with epilepsy: systematic review and suggestions for clinical management. Epilepsy Behav., 2005, 7(2), 161-171.
[] [PMID: 16054870]
Gur-Ozmen, S.; Leibetseder, A.; Cock, H.R.; Agrawal, N.; von Oertzen, T.J. Screening of anxiety and quality of life in people with epilepsy. Seizure, 2017, 45, 107-113.
[] [PMID: 27984808]
Gaitatzis, A.; Carroll, K.; Majeed, A.; W Sander, J. The epidemiology of the comorbidity of epilepsy in the general population. Epilepsia, 2004, 45(12), 1613-1622.
[] [PMID: 15571520]
Beyenburg, S.; Stoffel-Wagner, B.; Bauer, J.; Watzka, M.; Blümcke, I.; Bidlingmaier, F.; Elger, C.E. Neuroactive steroids and seizure susceptibility. Epilepsy Res., 2001, 44(2-3), 141-153.
[] [PMID: 11325570]
Mula, M.; Pini, S.; Cassano, G.B. The role of anticonvulsant drugs in anxiety disorders: a critical review of the evidence. J. Clin. Psychopharmacol., 2007, 27(3), 263-272.
[] [PMID: 17502773]
Mula, M. Treatment of anxiety disorders in epilepsy: an evidence-based approach. Epilepsia, 2013, 54(Suppl. 1), 13-18.
[] [PMID: 23458462]
Charney, D.S. Neuroanatomical circuits modulating fear and anxiety behaviors. Acta Psychiatr. Scand. Suppl., 2003, 108(417), 38-50.
[] [PMID: 12950435]
Martin, J.L.R.; Sainz-Pardo, M.; Furukawa, T.A.; Martín-Sánchez, E.; Seoane, T.; Galán, C. Benzodiazepines in generalized anxiety disorder: heterogeneity of outcomes based on a systematic review and meta-analysis of clinical trials. J. Psychopharmacol. (Oxford), 2007, 21(7), 774-782.
[] [PMID: 17881433]
Isaeva, E.; Hernan, A.; Isaev, D.; Holmes, G.L. Thrombin facilitates seizures through activation of persistent sodium current. Ann. Neurol., 2012, 72(2), 192-198.
[] [PMID: 22926852]
Maggio, N.; Cavaliere, C.; Papa, M.; Blatt, I.; Chapman, J.; Segal, M. Thrombin regulation of synaptic transmission: implications for seizure onset. Neurobiol. Dis., 2013, 50, 171-178.
[] [PMID: 23103417]
Semenikhina, M.; Bogovyk, R.; Fedoriuk, M.; Nikolaienko, O.; Al Kury, L.T.; Savotchenko, A.; Krishtal, O.; Isaeva, E. Inhibition of protease-activated receptor 1 ameliorates behavioral deficits and restores hippocampal synaptic plasticity in a rat model of status epilepticus. Neurosci. Lett., 2019, 692, 64-68.
[] [PMID: 30391321]
Nicoll, RA; Malenka, RC, 2002, 1-11.
Gingrich, M.B.; Junge, C.E.; Lyuboslavsky, P.; Traynelis, S.F. Potentiation of NMDA receptor function by the serine protease thrombin. J. Neurosci., 2000, 20(12), 4582-4595.
[] [PMID: 10844028]
Almonte, A.G.; Qadri, L.H.; Sultan, F.A.; Watson, J.A.; Mount, D.J.; Rumbaugh, G.; Sweatt, J.D. Protease-activated receptor-1 modulates hippocampal memory formation and synaptic plasticity. J. Neurochem., 2013, 124(1), 109-122.
[] [PMID: 23113835]
Chen, B.; Friedman, B.; Whitney, M.A.; Winkle, J.A.V.; Lei, I-F.; Olson, E.S.; Cheng, Q.; Pereira, B.; Zhao, L.; Tsien, R.Y.; Lyden, P.D. Thrombin activity associated with neuronal damage during acute focal ischemia. J. Neurosci., 2012, 32(22), 7622-7631.
[] [PMID: 22649241]
Manaenko, A.; Sun, X.; Kim, C.H.; Yan, J.; Ma, Q.; Zhang, J.H. PAR-1 antagonist SCH79797 ameliorates apoptosis following surgical brain injury through inhibition of ASK1-JNK in rats. Neurobiol. Dis., 2013, 50, 13-20.
[] [PMID: 23000356]
Bogovyk, R.; Lunko, O.; Fedoriuk, M.; Isaev, D.; Krishtal, O.; Holmes, G.L.; Isaeva, E. Effects of protease-activated receptor 1 inhibition on anxiety and fear following status epilepticus. Epilepsy Behav., 2017, 67, 66-69.
[] [PMID: 28088683]
Ferreira, F.; Bota, R.G.; Bonet-Costa, V.; Sun, P.Y.; Davies, K.J.A. The role of oxidative stress in anxiety disorder: cause or consequence? Free Radic. Res., 2018, 52, 737-750.
Lichtenberg, D.; Pinchuk, I. Oxidative stress, the term and the concept. Biochem. Biophys. Res. Commun., 2015, 461(3), 441-444.
[] [PMID: 25911322]
Jindal, A.; Mahesh, R.; Bhatt, S. Etazolate, a phosphodiesterase 4 inhibitor reverses chronic unpredictable mild stress-induced depression-like behavior and brain oxidative damage. Pharmacol. Biochem. Behav., 2013, 105, 63-70.
[] [PMID: 23384434]
Bouvier, E.; Brouillard, F.; Molet, J.; Claverie, D.; Cabungcal, J.H.; Cresto, N.; Doligez, N.; Rivat, C.; Do, K.Q.; Bernard, C.; Benoliel, J.J.; Becker, C. Nrf2-dependent persistent oxidative stress results in stress-induced vulnerability to depression. Mol. Psychiatry, 2017, 22(12), 1701-1713.
[] [PMID: 27646262]
Tariq, M.; Ahmad, M.; Moutaery, K.A.; Deeb, S.A. Pentoxifylline ameliorates lithium-pilocarpine induced status epilepticus in young rats. Epilepsy Behav., 2008, 12(3), 354-365.
[] [PMID: 18203664]
Ahmad, M.; Abu-Taweel, G.M.; Aboshaiqah, A.E.; Ajarem, J.S. The effects of quinacrine, proglumide, and pentoxifylline on seizure activity, cognitive deficit, and oxidative stress in rat lithium-pilocarpine model of status epilepticus. Oxid. Med. Cell. Longev., 2014, 2014630509
[] [PMID: 25478062]
Zhang, G.; Li, S.; Kang, Y.; Che, J.; Cui, R.; Song, S.; Cui, H.; Shi, G. Enhancement of dopaminergic activity and region-specific activation of Nrf2-ARE pathway by intranasal supplements of testosterone propionate in aged male rats. Horm. Behav., 2016, 80, 103-116.
[] [PMID: 26893122]
Tsou, Y.H.; Shih, C.T.; Ching, C.H.; Huang, J.Y.; Jen, C.J.; Yu, L.; Kuo, Y.M.; Wu, F.S.; Chuang, J.I. Treadmill exercise activates Nrf2 antioxidant system to protect the nigrostriatal dopaminergic neurons from MPP+ toxicity. Exp. Neurol., 2015, 263, 50-62.
[] [PMID: 25286336]
Kumar, H.; Koppula, S.; Kim, I-S.; More, S.V.; Kim, B-W.; Choi, D-K. Nuclear factor erythroid 2-related factor 2 signaling in Parkinson disease: a promising multi therapeutic target against oxidative stress, neuroinflammation and cell death. CNS Neurol. Disord. Drug Targets, 2012, 11(8), 1015-1029.
[] [PMID: 23244425]
Innamorato, N.G.; Jazwa, A.; Rojo, A.I.; García, C.; Fernández-Ruiz, J.; Grochot-Przeczek, A.; Stachurska, A.; Jozkowicz, A.; Dulak, J.; Cuadrado, A. Different susceptibility to the Parkinson’s toxin MPTP in mice lacking the redox master regulator Nrf2 or its target gene heme oxygenase-1. PLoS One, 2010, 5(7)e11838
[] [PMID: 20676377]
Helmstaedter, C.; Witt, J.A. Epilepsy and cognition - A bidirectional relationship? Seizure, 2017, 49, 83-89.
[] [PMID: 28284559]
Butler, C.R.; Zeman, A.Z. Recent insights into the impairment of memory in epilepsy: transient epileptic amnesia, accelerated long-term forgetting and remote memory impairment. Brain, 2008, 131(Pt 9), 2243-2263.
[] [PMID: 18669495]
Holmes, G.L. Cognitive impairment in epilepsy: the role of network abnormalities. Epileptic Disord., 2015, 17(2), 101-116.
[] [PMID: 25905906]
Singh, T.; Bagga, N.; Kaur, A.; Kaur, N.; Gawande, D.Y.; Goel, R.K. Agmatine for combined treatment of epilepsy, depression and cognitive impairment in chronic epileptic animals. Biomed. Pharmacother., 2017, 92, 720-725.
[] [PMID: 28586743]
Reis, DJ; Regunathan, S Is agmatine a novel neurotransmitter in brain, 2000, 21, 31-4.
Law, A.; Gauthier, S.; Quirion, R. Say NO to Alzheimer’s disease: the putative links between nitric oxide and dementia of the Alzheimer’s type. Brain Res. Brain Res. Rev., 2001, 35(1), 73-96.
[] [PMID: 11245887]
Law, A.; Doré, S.; Blackshaw, S.; Gauthier, S.; Quirion, R. Alteration of expression levels of neuronal nitric oxide synthase and haem oxygenase-2 messenger RNA in the hippocampi and cortices of young adult and aged cognitively unimpaired and impaired Long-Evans rats. Neuroscience, 2000, 100(4), 769-775.
[] [PMID: 11036210]
Law, A.; O’Donnell, J.; Gauthier, S.; Quirion, R. Neuronal and inducible nitric oxide synthase expressions and activities in the hippocampi and cortices of young adult, aged cognitively unimpaired, and impaired Long-Evans rats. Neuroscience, 2002, 112(2), 267-275.
[] [PMID: 12044445]
Liu, P.; Smith, P.F.; Appleton, I.; Darlington, C.L.; Bilkey, D.K. Age-related changes in nitric oxide synthase and arginase in the rat prefrontal cortex. Neurobiol. Aging, 2004, 25(4), 547-552.
[] [PMID: 15013576]
Liu, P.; Jing, Y.; Zhang, H. Age-related changes in arginine and its metabolites in memory-associated brain structures. Neuroscience, 2009, 164(2), 611-628.
[] [PMID: 19699269]
Arteni, N.S.; Lavinsky, D.; Rodrigues, A.L.; Frison, V.B.; Netto, C.A. Agmatine facilitates memory of an inhibitory avoidance task in adult rats. Neurobiol. Learn. Mem., 2002, 78(2), 465-469.
[] [PMID: 12431430]
Moosavi, M.; Khales, G.Y.; Abbasi, L.; Zarifkar, A.; Rastegar, K. Agmatine protects against scopolamine-induced water maze performance impairment and hippocampal ERK and Akt inactivation. Neuropharmacology, 2012, 62(5-6), 2018-2023.
[] [PMID: 22248637]
Rushaidhi, M.; Collie, N.D.; Zhang, H.; Liu, P. Agmatine selectively improves behavioural function in aged male Sprague-Dawley rats. Neuroscience, 2012, 218, 206-215.
[] [PMID: 22609940]
Rushaidhi, M.; Zhang, H.; Liu, P. Effects of prolonged agmatine treatment in aged male Sprague-Dawley rats. Neuroscience, 2013, 234, 116-124.
[] [PMID: 23318245]
Luszczki, J.J.; Czernecki, R.; Wojtal, K.; Borowicz, K.K.; Czuczwar, S.J. Agmatine enhances the anticonvulsant action of phenobarbital and valproate in the mouse maximal electroshock seizure model. J. Neural Transm. (Vienna), 2008, 115(11), 1485-1494.
[] [PMID: 18379717]
Freitas, A.E.; Neis, V.B.; Rodrigues, A.L.S.; Rodrigues, S. Agmatine, a potential novel therapeutic strategy for depression. Eur. Neuropsychopharmacol., 2016, 26(12), 1885-1899.
[] [PMID: 27836390]
Feng, Y; Leblanc, MH; Regunathan, S Agmatine reduces extracellular glutamate during pentylenetetrazole-induced seizures in rat brain : A potential mechanism for the anticonvulsive effects, 2005, 390, 129-33.
Ahn, K.S.; Aggarwal, B.B. Transcription factor NF-kappaB: a sensor for smoke and stress signals. Ann. N. Y. Acad. Sci., 2005, 1056, 218-233.
[] [PMID: 16387690]
Jones, S.V.; Kounatidis, I. Nuclear factor-kappa B and Alzheimer disease, unifying genetic and environmental risk factors from cell to humans. Front. Immunol., 2017, 8, 1805.
[] [PMID: 29312321]
Cai, Z.; Zhao, Y.; Yao, S.; Bin Zhao, B. Increases in β-amyloid protein in the hippocampus caused by diabetic metabolic disorder are blocked by minocycline through inhibition of NF-κB pathway activation. Pharmacol. Rep., 2011, 63(2), 381-391.
[] [PMID: 21602593]
Chen, C.H.; Zhou, W.; Liu, S.; Deng, Y.; Cai, F.; Tone, M.; Tone, Y.; Tong, Y.; Song, W. Increased NF-κB signalling up-regulates BACE1 expression and its therapeutic potential in Alzheimer’s disease. Int. J. Neuropsychopharmacol., 2012, 15(1), 77-90.
[] [PMID: 21329555]
Wang, Z.H.; Mong, M.C.; Yang, Y.C.; Yin, M.C. Asiatic acid and maslinic acid attenuated kainic acid-induced seizure through decreasing hippocampal inflammatory and oxidative stress. Epilepsy Res., 2018, 139, 28-34.
[] [PMID: 29156327]
Liu, H.J.; Lai, X.; Xu, Y.; Miao, J.K.; Li, C.; Liu, J.Y.; Hua, Y.Y.; Ma, Q.; Chen, Q. α-Asarone attenuates cognitive deficit in a pilocarpine-induced status epilepticus rat model via a decrease in the nuclear factor-κB activation and reduction in microglia neuroinflammation. Front. Neurol., 2017, 8, 661.
[] [PMID: 29312110]
Gu, Q.; Du, H.; Ma, C.; Fotis, H.; Wu, B.; Huang, C.; Schwarz, W. Effects of alpha-asarone on the glutamate transporter EAAC1 in Xenopus oocytes. Planta Med., 2010, 76(6), 595-598.
[] [PMID: 19937551]
Rajput, S.B.; Tonge, M.B.; Karuppayil, S.M. An overview on traditional uses and pharmacological profile of Acorus calamus Linn. (Sweet flag) and other Acorus species. Phytomedicine, 2014, 21(3), 268-276.
[] [PMID: 24200497]
Marchi, N.; Granata, T.; Janigro, D. Inflammatory pathways of seizure disorders. Trends Neurosci., 2014, 37(2), 55-65.
[] [PMID: 24355813]
Kim, B.W.; Koppula, S.; Kumar, H.; Park, J.Y.; Kim, I.W.; More, S.V.; Kim, I.S.; Han, S.D.; Kim, S.K.; Yoon, S.H.; Choi, D.K. α-Asarone attenuates microglia-mediated neuroinflammation by inhibiting NF kappa B activation and mitigates MPTP-induced behavioral deficits in a mouse model of Parkinson’s disease. Neuropharmacology, 2015, 97, 46-57.
[] [PMID: 25983275]
Tan, X.; Gu, J.; Zhao, B.; Wang, S.; Yuan, J.; Wang, C.; Chen, J.; Liu, J.; Feng, L.; Jia, X. Ginseng improves cognitive deficit via the RAGE/NF-κB pathway in advanced glycation end product-induced rats. J. Ginseng Res., 2015, 39(2), 116-124.
[] [PMID: 26045684]

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