Research Article| Volume 24, ISSUE 2, P199-206, June 2012

Download started.


Evaluation of the antiepileptic effect of curcumin and Nigella sativa oil in the pilocarpine model of epilepsy in comparison with valproate


      The present study aimed to investigate the effect of curcumin and Nigella sativa oil (NSO) on amino acid neurotransmitter alterations and the histological changes induced by pilocarpine in the hippocampus and cortex of rats. Epilepsy was induced by i.p. injection of pilocarpine, and the animals were left for 22 days to establish spontaneous recurrent seizures. They were then treated with curcumin, NSO or valproate for 21 days. Pilocarpine induced a significant increase in hippocampal aspartate and a significant decrease in glycine and taurine levels. In the cortex, a significant increase in aspartate, glutamate, GABA, glycine, and taurine levels was obtained after pilocarpine injection. Treatment of pilocarpinized rats with curcumin and valproate ameliorated most of the changes in amino acid concentrations and reduced the histopathological abnormalities induced by pilocarpine. N. sativa oil failed to improve the pilocarpine-induced abnormalities. This may explain the antiepileptic effect of curcumin and suggest its use as an anticonvulsant.


      • Neurochemical and histopathological changes are induced in rat model of epilepsy.
      • Treatment of animal model with curcumin and Nigella sativa oil improves seizures.
      • Comparison of the results of curcumin and Nigella sativa oil with valproate.
      • Curcumin improves the histopathological and neurochemical changes.
      • Nigella sativa oil fails to restore the changes induced in rat model of epilepsy.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Epilepsy & Behavior
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Lowenstein D.H.
        Seizures and epilepsy.
        in: Kasper D.L. Braunwald E. Fauci A.S. Hauser S.L. Longo D.L. Jameson J.L. Harrison's principles of internal medicine. McGraw-Hill, USA2008: 2357-2372
        • Perry T.L.
        • Hansen S.
        Amino acid abnormalities in epileptogenic foci.
        Neurology. 1981; 31: 872-876
        • Bradford H.F.
        Glutamate, GABA and epilepsy.
        Prog Neurobiol. 1995; 47: 477-511
        • Pena F.
        • Tapia R.
        Seizures and neurodegeneration induced by 4-aminopyridine in rat hippocampus in vivo: role of glutamate- and GABA-mediated neurotransmission and of ion channels.
        Neuroscience. 2000; 101: 547-561
        • Khongsombat O.
        • Watanabe H.
        • Tantisira B.
        • Patarapanich C.
        • Tantisira M.H.
        Acute effects of N-(2-propylpentanoyl)urea on hippocampal amino acid neurotransmitters in pilocarpine-induced seizure in rats.
        Epilepsy Res. 2008; 79: 151-157
        • Brodie M.J.
        • Dichter M.A.
        Antiepileptic drugs.
        N Engl J Med. 1996; 334: 168-175
        • Löscher W.
        Effects of the antiepileptic drug valproate on metabolism and function of inhibitory and excitatory amino acid in the brain.
        Neurochem Res. 1993; 18: 485-502
        • Baldino F.
        • Geller H.M.
        Sodium valproate enhancement of γ-aminobutyric (GABA) inhibition: electrophysiological evidence for anticonvulsant activity.
        J Pharmacol Exp Ther. 1981; 217: 445-450
        • Chapman A.
        • Keane P.E.
        • Meldrum B.S.
        • Simiand J.
        • Vernieres J.C.
        Mechanisms of anticonvulsant action of valproate.
        Prog Neurobiol. 1982; 19: 315-359
        • Johannessen C.U.
        Mechanisms of action of valproate: a commentatory.
        Neurochem Int. 2000; 37: 103-110
        • Löscher W.
        • Vetter M.
        In vivo effects of aminooxyacetic acid and valproic acid on nerve terminal (synaptosomal) GABA levels in discrete brain areas of the rat. Correlation to pharmacological activities.
        Biochem Pharmacol. 1985; 34: 1747-1756
        • McLean M.J.
        • Macdonald R.L.
        Sodium valproate, but not ethosuximide, produces use- and voltage-dependent limitation of high frequency repetitive firing of action potentials of mouse central neurons in cell culture.
        J Pharmacol Exp Ther. 1986; 237: 1001-1011
        • Taverna S.
        • Mantegazza M.
        • Franceschetti S.
        • Avanzini G.
        Valproate selectively reduces the persistent fraction of Na+ current in neocortical neurons.
        Epilepsy Res. 1998; 32: 304-308
        • Gean P.W.
        • Huang C.C.
        • Hung C.R.
        • Tsai J.J.
        Valproic acid suppresses the synaptic response mediated by the NMDA receptors in rat amygdalar slices.
        Brain Res Bull. 1994; 33: 333-336
        • Gobbi G.
        • Janiri L.
        Sodium- and magnesium-valproate in vivo modulate glutamatergic and GABAergic synapses in the medial prefrontal cortex.
        Psychopharmacology (Berl). 2006; 185: 255-262
        • Ko G.Y.
        • Brown-Croyts L.M.
        • Teyler T.J.
        The effects of anticonvulsant drugs on NMDA-EPSP, AMPAEPSP, and GABA-IPSP in the rat hippocampus.
        Brain Res Bull. 1997; 42: 297-302
        • Martin E.D.
        • Pozo M.A.
        Valproate reduced excitatory postsynaptic currents in hippocampal CA1 pyramidal neurons.
        Neuropharmacology. 2004; 46: 555-561
        • Turski L.
        • Niemann W.
        • Stephens D.N.
        Differential effects of antiepileptic drugs and beta-carbolines on seizures induced by excitatory amino acids.
        Neuroscience. 1990; 39: 799-807
        • Zeise M.L.
        • Kasparow S.
        • Zieglgansberger W.
        Valproate suppresses N-methyl-d-aspartate-evoked, transient depolarizations in the rat neocortex in vitro.
        Brain Res. 1991; 544: 345-348
        • Pitkanen A.
        • Sutula T.P.
        Is epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal-lobe epilepsy.
        Lancet Neurol. 2002; 1: 173-181
        • Lindekens H.
        • Smolders I.
        • Khan G.M.
        • Bialer M.
        • Ebinger G.
        • Michotte Y.
        In vivo study of the effect of valpromide and valnoctamide in the pilocarpine rat model of focal epilepsy.
        Pharm Res. 2000; 17: 1408-1413
        • Shinnar S.
        • Berg A.T.
        Does antiepileptic drug therapy prevent the development of “chronic” epilepsy?.
        Epilepsia. 1996; 37: 701-708
        • Sumanont Y.
        • Murakami Y.
        • Tohda M.
        • Vajragupta O.
        • Watanabe H.
        • Matsumoto K.
        Effects of manganese complexes of curcumin and diacetylcurcumin on kainic acid-induced neurotoxic responses in the rat hippocampus.
        Biol Pharm Bull. 2007; 30: 1732-1739
        • Shin H.J.
        • Lee J.Y.
        • Son E.
        • et al.
        Curcumin attenuates the kainic acid-induced hippocampal cell death in the mice.
        Neurosci Lett. 2007; 416: 49-54
        • Bharal N.
        • Sahaya K.
        • Jain S.
        • Mediratta P.K.
        • Sharma K.K.
        Curcumin has anticonvulsant activity on increasing current electroshock seizures in mice.
        Phytother Res. 2008; 22: 1660-1664
        • Jyoti A.
        • Sethi P.
        • Sharma D.
        Curcumin protects against electrobehavioral progression of seizures in iron induced experimental model of epileptogenesis.
        Epilepsy Behav. 2009; 14: 300-308
        • Mehla J.
        • Reeta K.H.
        • Gupta P.
        • Gupta Y.K.
        Protective effect of curcumin against seizures and cognitive impairment in a pentylenetetrazole-kindled epileptic rat model.
        Life Sci. 2010; 87: 596-603
        • Aboul Ezz H.S.
        • Khadrawy Y.A.
        • Noor N.A.
        The neuroprotective effect of curcumin and Nigella sativa oil against oxidative stress in the pilocarpine model of epilepsy: a comparison with valproate.
        Neurochem Res. 2011; 36: 2195-2204
        • Ilhan A.
        • Gurel A.
        • Armutcu F.
        • Kamisli S.
        • Iraz M.
        Antiepileptogenic and antioxidant effects of Nigella sativa oil against pentylenetetrazol-induced kindling in mice.
        Neuropharmacology. 2005; 49: 456-464
        • Guha D.
        • Biswas D.
        • Purkayastha S.
        Suppression of penicillin-induced epileptiform activity by Nigella sativa: possible mediation by neurotransmitters.
        Biog Amines. 2005; 19: 309-321
        • Al-Naggar T.B.
        • Gòmez-Serranillos M.
        • Carretero P.M.E.
        • Villar A.M.
        Neuropharmacological activity of Nigella sativa L. extracts.
        J Ethnopharmacol. 2003; 88: 63-68
        • Cavalheiro E.A.
        • Leite J.P.
        • Bortolotto Z.A.
        • Turski W.A.
        • Ikonomidou C.
        • Turski L.
        Long-term effects of pilocarpine in rats: structural damage of the brain triggers kindling and spontaneous recurrent seizures.
        Epilepsia. 1991; 32: 778-782
        • Mello L.E.A.M.
        • Cavalheiro E.A.
        • Tan A.M.
        • et al.
        Circuit mechanisms of seizures in the pilocarpine model of chronic epilepsy: cell loss and mossy fiber sprouting.
        Epilepsia. 1993; 34: 985-995
        • Turski L.
        • Ikonomidou C.
        • Turski W.A.
        • Bortolotto Z.A.
        • Cavalheiro E.A.
        Cholinergic mechanisms and epileptogenesis. The seizures induced by pilocarpine: a novel experimental model of intractable epilepsy.
        Synapse. 1989; 3: 154-171
        • Turski W.A.
        • Cavalheiro E.A.
        • Schwarz M.
        • Czuczwar S.J.
        • Kleinrok Z.
        • Turski L.
        Limbic seizures produced by pilocarpine in rats: behavioural, electroencephalographic and neuropathological study.
        Behav Brain Res. 1983; 9: 315-335
        • Turski W.A.
        • Czuczwar S.J.
        • Kleinrok Z.
        • Turski L.
        Cholinomimetics produce seizures and brain damage in rats.
        Experientia. 1983; 39: 1408-1411
        • Cavalheiro E.A.
        • Santos N.F.
        • Priel M.R.
        The pilocarpine model of epilepsy in mice.
        Epilepsia. 1996; 37: 1015-1019
        • Morrisett R.A.
        • Jope R.S.
        • Snead O.C.
        Effects of drugs on the initiation and maintenance of status epilepticus induced by administration of pilocarpine to lithium-pretreated rats.
        Exp Neurol. 1987; 97: 193-200
        • Turski W.A.
        • Cavalheiro E.A.
        • Coimbra C.
        • Berzagh M.P.
        • Ikonomidou-Turski C.
        • Turski L.
        Only certain antiepileptic drugs prevent seizures induced by pilocarpine.
        Brain Res Rev. 1987; 12: 281-305
        • Cavalheiro E.A.
        • Fernandes M.J.
        • Turski L.
        • Naffah-Mazzacoratti M.G.
        Spontaneous recurrent seizures in rats: amino acid and monoamine determination in the hippocampus.
        Epilepsia. 1994; 35: 1-11
        • Wilson C.L.
        • Maidment N.T.
        • Shomer M.H.
        • et al.
        Comparison of seizure-related amino acid release in human epileptic hippocampus versus a chronic, kainate rat model of hippocampal epilepsy.
        Epilepsy Res. 1996; 26: 245-254
        • Williams M.B.
        • Jope R.S.
        Protein synthesis inhibitors attenuate seizures induced in rats by lithium plus pilocarpine.
        Exp Neurol. 1994; 129: 169-173
        • Ishrat T.
        • Hoda M.N.
        • Khan M.B.
        • et al.
        Amelioration of cognitive deficits and neurodegeneration by curcumin in rat model of sporadic dementia of Alzheimer's type (SDAT).
        Eur Neuropsychopharmacol. 2009; 19: 636-647
        • Abdel-Zaher A.O.
        • Abdel-Rahman M.S.
        • ELwasei F.M.
        Blockade of nitric oxide overproduction and oxidative stress by Nigella sativa oil attenuates morphine-induced tolerance and dependence in mice.
        Neurochem Res. 2010; 35: 1557-1565
        • Màrquez F.J.
        • Quesada A.R.
        • Sάnchez-Jiménez F.
        • Múñez De Castro I.
        Determination of 27 dansyl amino acid derivatives in biological fluids by reversed-phase high-performance liquid chromatography.
        J Chromatogr. 1986; 380: 275-283
        • Tapuhi Y.
        • Schmidt D.E.
        • Linder W.
        • Karger B.L.
        Dansylation of amino acids for high-performance liquid chromatography analysis.
        Anal Biochem. 1981; 115: 123-129
        • Arida R.M.
        • Scorza F.A.
        • Peres C.A.
        • Cavalheiro E.A.
        The course of untreated seizures in the pilocarpine model of epilepsy.
        Epilepsy Res. 1999; 34: 99-107
        • Veliskova J.
        Behavioral characterization of seizures in rats.
        in: Pitkänen A. Schwartzkroin P.A. Moshé S.L. Models of seizures and epilepsy. Elsevier Academic Press, Burlington2006: 601-611
        • Löscher W.
        Valproate: a reappraisal of its pharmacodynamic properties and mechanisms of action.
        Prog Neurobiol. 1999; 58: 31-59
        • Green J.R.
        • Halpern L.M.
        • Van Niel S.
        Alterations in the activity of selected enzymes in the chronic isolated cerebral cortex of cat.
        Brain. 1970; 93: 57-64
        • Avoli M.
        • Barbarosie M.
        Interictal–ictal interactions and limbic seizure generation.
        Rev Neurol (Paris). 1999; 155: 468-471
        • Zhang L.H.
        • Gong N.
        • Fei D.
        • Xu L.
        • Xu T.L.
        Glycine uptake regulates hippocampal network activity via glycine receptor-mediated tonic inhibition.
        Neuropsychopharmacology. 2008; 33: 701-711
        • Van Gelder N.M.
        Contributions of basic neurochemistry towards a novel concept of epilepsy.
        Neurochem Res. 1987; 12: 111-119
        • Feldblum A.
        • Ackermann R.F.
        • Tobin A.J.
        Long-term increase of glutamate decarboxylase mRNA in a rat model of temporal lobe epilepsy.
        Neuron. 1990; 5: 361-371
        • Baran H.
        • Kepplinger B.
        • Draxler M.
        • Skofitsch G.
        Choline acetyltransferase, glutamic acid decarboxylase and somatostatin in the kainic acid model for chronic temporal lobe epilepsy.
        Neurosignals. 2004; 13: 290-297
        • Clifford D.B.
        • Olney J.W.
        • Maniotis A.
        • Collins R.C.
        • Zorumski C.F.
        The functional anatomy and pathology of lithium-pilocarpine and high-dose pilocarpine seizures.
        Neuroscience. 1987; 23: 953-968
        • Chapman A.G.
        Cerebral energy metabolism and seizures.
        in: Pedley T.A. Meldrum B.S. Recent advances in epilepsy. Churchill Livingstone, Edinburgh1985: 19-63
        • Chowdhury G.M.
        • Gupta M.
        • Gibson K.M.
        • Patel A.B.
        • Behar K.L.
        Altered cerebral glucose and acetate metabolism in succinic semialdehyde dehydrogenase-deficient mice: evidence for glial dysfunction and reduced glutamate/glutamine cycling.
        J Neurochem. 2007; 103: 2077-2091
        • Bala K.
        • Tripathy B.C.
        • Sharma D.
        Neuroprotective and anti-ageing effects of curcumin in aged rat brain regions.
        Biogerontology. 2006; 7: 81-89
        • Lim G.P.
        • Chu T.
        • Yang F.
        • Beech W.
        • Frautschy S.A.
        • Cole G.M.
        The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse.
        J Neurosci. 2001; 21: 8370-8377
        • Bishnoi M.
        • Chopra K.
        • Kulkarni S.K.
        Protective effect of curcumin, the active principle of turmeric (Curcuma longa) in haloperidol-induced orofacial dyskinesia and associated behavioural, biochemical and neurochemical changes in rat brain.
        Pharmacol Biochem Behav. 2008; 88: 511-522
        • Matteucci A.
        • Frank C.
        • Domenici M.R.
        • et al.
        Curcumin treatment protects rat retinal neurons against excitotoxicity: effect on N-methyl-d-aspartate-induced intracellular Ca2+ increase.
        Exp Brain Res. 2005; 167: 641-648
        • Suh H.W.
        • Kang S.
        • Kwon K.S.
        Curcumin attenuates glutamate-induced HT22 cell death by suppressing MAP kinase signaling.
        Mol Cell Biochem. 2007; 298: 187-194
        • Bradford H.F.
        • Ward H.K.
        • Thomas A.J.
        Glutamine — a major substrate for nerve endings.
        J Neurochem. 1978; 30: 1453-1459
        • Pyrzanowska J.
        • Piechal A.
        • Blecharz-Klin K.
        • et al.
        The influence of the long-term administration of Curcuma longa extract on learning and spatial memory as well as the concentration of brain neurotransmitters and level of plasma corticosterone in aged rats.
        Pharmacol Biochem Behav. 2010; 95: 351-358
        • Del Arco A.
        • Segovia G.
        • Prieto L.
        • Mora F.
        Endogenous glutamate–taurine interaction in striatum and nucleus accumbens of the freely moving rat: studies during the normal process of aging.
        Mech Ageing Dev. 2001; 122: 401-414
        • Foos T.M.
        • Wu J.Y.
        The role of taurine in the central nervous system and the modulation of intracellular calcium homeostasis.
        Neurochem Res. 2002; 27: 21-26
        • El-Naggar T.
        • Gómez-Serranillos M.P.
        • Palomino O.
        • Arce C.
        • Carretero M.E.
        Nigella sativa L. seed extract modulates the neurotransmitter amino acids release in cultured neurons in vitro.
        J Biomed Biotechnol. 2010; 2101: 398312
        • Löscher W.
        • Horstermann D.
        Differential effects of vigabatrin, gamma-acetylenic GABA, aminooxyacetic acid, and valproate on levels of various amino acids in rat brain regions and plasma.
        Naunyn Schmiedebergs Arch Pharmacol. 1994; 349: 270-278
        • Safar M.M.
        • Abdallah D.M.
        • Arafa N.M.
        • Abdel-Aziz M.T.
        Magnesium supplementation enhances the anticonvulsant potential of valproate in pentylenetetrazol-treated rats.
        Brain Res. 2010; 133: 58-64
        • Li Z.
        • Zhang X.
        • Luc X.
        • Zhong M.
        • Ji Y.
        Dynamic release of amino acid transmitters induced by valproate in PTZ-kindled epileptic rat hippocampus.
        Neurochem Int. 2004; 44: 263-270
        • Rowley H.L.
        • Marsdern C.A.
        • Martin K.F.
        Differential effects of phenytoin and sodium valproate on seizure-induced changes in γ-aminobutyric acid and glutamate release in vivo.
        Eur J Pharmacol. 1995; 294: 541-546
        • Farber N.B.
        • Jiang X.P.
        • Heinkel C.
        • Nemmers B.
        Antiepileptic drugs and agents that inhibit voltage-gated sodium channels prevent NMDA antagonist neurotoxicity.
        Mol Psychiatry. 2002; 7: 726-733
        • Battistin L.
        • Varotto M.
        • Berlese G.
        • Roman G.
        Effects of some anticonvulsant drugs on brain GABA level and GAD and GABA-T activities.
        Neurochem Res. 1984; 9: 225-231
        • Löscher W.
        In vivo administration of valproate reduces the nerve terminal (synaptosomal) activity of GABA aminotransferase in discrete brain areas of rats.
        Neurosci Lett. 1993; 160: 177-180
        • O'Donnell T.
        • Rotzinger S.
        • Ulrich M.
        • Hanstock C.C.
        • Nakashima T.T.
        • Silverstonea P.H.
        Effects of chronic lithium and sodium valproate on concentrations of brain amino acids.
        Eur Neuropsychopharmacol. 2003; 13: 220-227
        • Guzmán D.C.
        • Vázquez I.E.
        • Mejía G.B.
        • et al.
        Effect of valproic acid on levels of GABA and glutamic acid in pentylenetetrazole-damaged rat brain.
        Proc West Pharmacol Soc. 2003; 46: 48-50
        • Karkar K.M.
        • Thio L.L.
        • Yamada K.A.
        Effects of seven clinically important antiepileptic drugs on inhibitory glycine receptor currents in hippocampal neurons.
        Epilepsy Res. 2004; 58: 27-35
        • Coyle J.T.
        • Puttfarcken P.
        Oxidative stress, glutamate, and neurodegenerative disorders.
        Science. 1993; 262: 689-695
        • Cavalheiro E.A.
        GAD-immunoreactive neurons are preserved in the hippocampus of rats with spontaneous recurrent seizures.
        Braz J Med Biol Res. 1990; 23: 555-558
        • Klitgaard H.
        • Matagne A.
        • Vanneste-Goemaere J.
        Pilocarpine-induced epileptogenesis in the rat: impact of initial duration of status epilepticus on electrophysiological and neuropathological alterations.
        Epilepsy Res. 2002; 51: 93-107
        • Mathern G.W.
        • Babb T.L.
        • Pretorius J.K.
        • Leite J.P.
        Reactive synaptogenesis and neuron densities for neuropeptide Y, somatostatin, and glutamate decarboxylase immunoreactivity in the epileptogenic human fascia dentata.
        J Neurosci. 1995; 15: 3990-4004
        • Liu A.
        • Nagao T.
        • Desjardis G.C.
        • Gloor P.
        • Avoli M.
        Quantitative evaluation of neuronal loss in the dorsal hippocampus in rats with long-term pilocarpine seizures.
        Epilepsy Res. 1994; 17: 237-247
        • Scharfman H.E.
        Epilepsy as an example of neural plasticity.
        Neuroscientist. 2002; 8: 154-173
        • Xu Y.
        • Ku B.
        • Cui L.
        • et al.
        Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats.
        Brain Res. 2007; 1162: 9-18
        • Bolanos A.R.
        • Sarkisian M.
        • Yang Y.
        • et al.
        Comparison of valproate and phenobarbital treatment after status epilepticus in rats.
        Neurology. 1998; 51: 41-48
        • Silver J.M.
        • Shin C.
        • McNamara J.O.
        Antiepileptogenic effects of conventional anticonvulsants in the kindling model of epilespy.
        Ann Neurol. 1991; 29: 356-363
        • Hashimoto R.
        • Hough C.
        • Nakazawa T.
        • Yamamoto T.
        • Chuang D.M.
        Lithium protection against glutamate excitotoxicity in rat cerebral cortical neurons: involvement of NMDA receptor inhibition possibly by decreasing NR2B tyrosine phosphorylation.
        J Neurochem. 2002; 80: 589-597
        • Laeng P.
        • Pitts R.L.
        • Lemire A.L.
        • et al.
        The mood stabilizer valproic acid stimulates GABA neurogenesis from rat forebrain stem cells.
        J Neurochem. 2004; 91: 238-251
        • Hao Y.
        • Creson T.
        • Zhang L.
        • et al.
        Mood stabilizer valproate promotes ERK pathway-dependent cortical neuronal growth and neurogenesis.
        J Neurosci. 2004; 24: 6590-6599
        • Hernandez R.
        • Pernandez Mde L.
        • Miranda G.
        • Suastegin R.
        Decrease of folic acid and cognitive alterations in patients with epilepsy treated with phenytoin or carbamazepine, pilot study.
        Rev Invest Clin. 2005; 57: 522-531
        • Shannon H.E.
        • Love P.L.
        Effects of antiepileptic drugs on learning as assessed by a repeated acquisition of response sequences task in rats.
        Epilepsy Behav. 2007; 10: 16-25
        • Butlin A.T.
        • Danta G.
        • Cook M.L.
        Anticonvulsant effects on the memory performance of epileptics.
        Clin Exp Neurol. 1984; 20: 27-35
        • Coenen A.M.L.
        • Konings G.M.L.G.
        • Aldenkamp A.P.
        • Renier W.O.
        • van Luijtelaar E.L.J.M.
        Effects of chronic use of carbamazepine and valproate on cognitive processes.
        J Epilepsy. 1995; 8: 250-254
        • Trimble M.R.
        • Thompson P.J.
        Sodium valproate and cognitive function.
        Epilepsia. 1984; 25: 60-64
        • Sgobio C.
        • Ghiglieri V.
        • Costa C.
        • et al.
        Hippocampal synaptic plasticity, memory, and epilepsy: effects of long-term valproic acid treatment.
        Biol Psychiatry. 2010; 67: 567-574
        • Conboy L.
        • Foley A.G.
        • O'Boyle N.M.
        • et al.
        Curcumin-induced degradation of PKCδ is associated with enhanced dentate NCAM PSA expression and spatial learning in adult and aged Wistar rats.
        Biochem Pharmacol. 2009; 77: 1254-1265