{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T14:02:21Z","timestamp":1777471341738,"version":"3.51.4"},"reference-count":66,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2017,4,25]],"date-time":"2017-04-25T00:00:00Z","timestamp":1493078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rational polytherapy in the treatment of refractory epilepsy has been the main therapeutic modality for several years. In treatment with two or more antiepileptic drugs (AEDs), it is of particular importance that AEDs be selected based on their high anticonvulsant properties, minimal side effects, and impact on the formation of new neurons. The aim of the study was to conduct an in vivo evaluation of the relationship between treatments with synthetic cannabinoid arachidonyl-2\u2032-chloroethylamide (ACEA) alone or in combination with valproic acid (VPA) and hippocampal neurogenesis in a mouse pilocarpine model of epilepsy. All studies were performed on adolescent male CB57\/BL mice with using the following drugs: VPA (10 mg\/kg), ACEA (10 mg\/kg), phenylmethylsulfonyl fluoride (PMSF\u2014a substance protecting ACEA against degradation by fatty acid hydrolase, 30 mg\/kg), pilocarpine (PILO, a single dose of 290 mg\/kg) and methylscopolamine (30 min before PILO to stop peripheral cholinergic effects of pilocarpine, 1 mg\/kg). We evaluated the process of neurogenesis after a 10-day treatment with ACEA and VPA, alone and in combination. We observed a decrease of neurogenesis in the PILO control group as compared to the healthy control mice. Furthermore, ACEA + PMSF alone and in combination with VPA significantly increased neurogenesis compared to the PILO control group. In contrast, VPA 10-day treatment had no impact on the level of neurons in comparison to the PILO control group. The combination of ACEA, PMSF and VPA considerably stimulated the process of creating new cells, particularly neurons, while chronic administration of VPA itself had no influence on neurogenesis in the mouse pilocarpine model of epilepsy. The obtained results enabled an in vivo evaluation of neurogenesis after treatment with antiepileptic drugs in an experimental model of epilepsy.<\/jats:p>","DOI":"10.3390\/ijms18050900","type":"journal-article","created":{"date-parts":[[2017,4,25]],"date-time":"2017-04-25T13:21:12Z","timestamp":1493126472000},"page":"900","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["A Long-Term Treatment with Arachidonyl-2\u2032-Chloroethylamide Combined with Valproate Increases Neurogenesis in a Mouse Pilocarpine Model of Epilepsy"],"prefix":"10.3390","volume":"18","author":[{"given":"Marta","family":"Andres-Mach","sequence":"first","affiliation":[{"name":"Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, 20-950 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miros\u0142aw","family":"Zagaja","sequence":"additional","affiliation":[{"name":"Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, 20-950 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Haratym-Maj","sequence":"additional","affiliation":[{"name":"Department of Physiopathology, Institute of Rural Health, Jaczewskiego 2, 20-950 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0613-6593","authenticated-orcid":false,"given":"Rados\u0142aw","family":"Rola","sequence":"additional","affiliation":[{"name":"Department of Physiopathology, Institute of Rural Health, Jaczewskiego 2, 20-950 Lublin, Poland"},{"name":"Department of Neurological Surgery, Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maciej","family":"Maj","sequence":"additional","affiliation":[{"name":"Department of Biopharmacy, Medical University of Lublin, Chodzki 4A, 20-090 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"Haratym","sequence":"additional","affiliation":[{"name":"Department of Anestesiology and Intensive Care Medicine, Hollycross Cancer Center, Artwi\u0144skiego 3, 25-734 Kielce, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Dudra-Jastrz\u0119bska","sequence":"additional","affiliation":[{"name":"Department of Physiopathology, Institute of Rural Health, Jaczewskiego 2, 20-950 Lublin, Poland"},{"name":"Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jarogniew","family":"\u0141uszczki","sequence":"additional","affiliation":[{"name":"Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, 20-950 Lublin, Poland"},{"name":"Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1159\/000360640","article-title":"Additive interactions between 1-methyl-1,2,3,4-tetrahydroisoquinoline and clobazam in the mouse maximal electroshock-induced tonic seizure model\u2014An isobolographic analysis for parallel dose-response relationship curves","volume":"93","author":"Zagaja","year":"2014","journal-title":"Pharmacology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ejphar.2006.07.037","article-title":"Arachidonyl-2\u2032-chloroethylamide, a highly selective cannabinoid CB1 receptor agonist, enhances the anticonvulsant action of valproate in the mouse maximal electroshock-induced seizure model","volume":"547","author":"Luszczki","year":"2006","journal-title":"Eur. J. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.pnpbp.2009.09.005","article-title":"Effect of arachidonyl-2\u2032-chloroethylamide, a selective cannabinoid CB1 receptor agonist, on the protective action of the various antiepileptic drugs in the mouse maximal electroshock-induced seizure model","volume":"34","author":"Luszczki","year":"2010","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1016\/j.pnpbp.2011.07.001","article-title":"Effects of WIN 55,212-2 mesylate (a synthetic cannabinoid) on the protective action of clonazepam, ethosuximide, phenobarbital and valproate against pentylenetetrazole-induced clonic seizures in mice","volume":"35","author":"Luszczki","year":"2011","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5274","DOI":"10.1021\/acs.jmedchem.5b00578","article-title":"Design, synthesis, and anticonvulsant activity of new hybrid compounds derived from 2-(2,5-dioxopyrrolidin-1-yl)propanamides and 2-(2,5-dioxopyrrolidin-1-yl)butanamides","volume":"58","author":"Zagaja","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"663","DOI":"10.2174\/0929867320666131119152201","article-title":"Pathophysiogenesis of mesial temporal lobe epilepsy: Is prevention of damage antiepileptogenic?","volume":"21","author":"Curia","year":"2014","journal-title":"Curr. Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1002\/ana.21463","article-title":"Sedative and anticonvulsant drugs suppress postnatal neurogenesis","volume":"64","author":"Stefovska","year":"2008","journal-title":"Ann. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.brainres.2010.06.061","article-title":"Levetiracetam suppresses development of spontaneous EEG seizures and aberrant neurogenesis following kainate-induced status epilepticus","volume":"1352","author":"Sugaya","year":"2010","journal-title":"Brain Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.brainres.2009.12.024","article-title":"Effects of lamotrigine and topiramate on hippocampal neurogenesis in experimental temporal-lobe epilepsy","volume":"1313","author":"Chen","year":"2010","journal-title":"Brain Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1111\/fcp.12061","article-title":"Analysis of the antiepileptic, ethosuximide impacts on neurogenesis of rat forebrain stem cells","volume":"28","author":"Sondossi","year":"2014","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.brainres.2015.07.028","article-title":"ACEA (a highly selective cannabinoid CB1 receptor agonist) stimulates hippocampal neurogenesis in mice treated with antiepileptic drugs","volume":"1624","author":"Zagaja","year":"2015","journal-title":"Brain Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5967","DOI":"10.1523\/JNEUROSCI.0110-07.2007","article-title":"Epigenetic modulation of seizure-induced neurogenesis and cognitive decline","volume":"27","author":"Jessberger","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Hill, E.J., Nagel, D.A., O\u2019Neil, J.D., Torr, E., Woehrling, E.K., Devitt, A., and Coleman, M.D. (2013). Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0058822"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.eplepsyres.2014.02.005","article-title":"Valproic acid in normal therapeutic concentration has no neuroprotective or differentiation influencing effects on long term expanded murine neural stem cells","volume":"108","author":"Brunn","year":"2014","journal-title":"Epilepsy Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.neuroscience.2009.11.073","article-title":"Valproic acid reduces spatial working memory and cell proliferation in the hippocampus","volume":"166","author":"Umka","year":"2010","journal-title":"Neuroscience"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3218","DOI":"10.1523\/JNEUROSCI.4050-14.2015","article-title":"Valproate-induced neurodevelopmental deficits in Xenopus laevis tadpoles","volume":"18","author":"James","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1124\/jpet.103.051920","article-title":"The endogenous cannabinoid system regulates seizure frequency and duration in a model of temporal lobe epilepsy","volume":"307","author":"Wallace","year":"2015","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.pnpbp.2012.07.001","article-title":"Effect of ACEA\u2014A selective cannabinoid CB1 receptor agonist on the protective action of different antiepileptic drugs in the mouse pentylenetetrazole-induced seizure model","volume":"39","author":"Zolkowska","year":"2012","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.nbd.2014.10.018","article-title":"Post-status epilepticus treatment with the cannabinoid agonist WIN 55,212-2 prevents chronic epileptic hippocampal damage in rats","volume":"73","author":"Cannon","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_20","first-page":"382","article-title":"Influence of arachidonyl-2\u2032-chloroethylamide, a selective cannabinoid CB1 receptor agonist, on the anticonvulsant and acute side-effect potentials of clobazam, lacosamide, and pregabalin in the maximal electroshock-induced seizure model and chimney test in mice","volume":"29","author":"Zagaja","year":"2013","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1017\/S1461145712001502","article-title":"The anxiolytic effect of cannabidiol on chronically stressed mice depends on hippocampal neurogenesis: Involvement of the endocannabinoid system","volume":"16","author":"Campos","year":"2013","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"11256","DOI":"10.1073\/pnas.1016442108","article-title":"Role of CB1 cannabinoid receptors on GABAergic neurons in brain aging","volume":"108","author":"Albayram","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1478-811X-8-12","article-title":"Cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis","volume":"17","author":"Wolf","year":"2010","journal-title":"Cell. Commun. Signal."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Noebels, J.L., Avoli, M., Rogawski, M.A., Olsen, R.W., and Delgado-Escueta, A.V. (2012). Neurogenesis and Epilepsy. Jasper\u2019s Basic Mechanisms of the Epilepsies, National Center for Biotechnology Information (US). [4th ed.].","DOI":"10.1093\/med\/9780199746545.001.0001"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/s11910-015-0616-3","article-title":"Neurogenesis in the hippocampus of patients with temporal lobe epilepsy","volume":"16","author":"Zhong","year":"2016","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6606","DOI":"10.1038\/ncomms7606","article-title":"Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline","volume":"6","author":"Cho","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"268","DOI":"10.5698\/1535-7511-16.4.268","article-title":"Neurogenesis in Epilepsy: Better to Burn Out or Fade Away?","volume":"16","author":"Danzer","year":"2016","journal-title":"Epilepsy Curr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6590","DOI":"10.1523\/JNEUROSCI.5747-03.2004","article-title":"Mood stabilizer valproate promotes ERK pathway-dependent cortical neuronal growth and neurogenesis","volume":"24","author":"Hao","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/S0924-9338(02)00696-X","article-title":"Antiepileptic drugs in schizophrenia: A review","volume":"17","author":"Libiger","year":"2002","journal-title":"Eur. Psychiatry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jad.2009.10.033","article-title":"Valproate for the treatment of acute bipolar depression: Systematic review and meta-analysis","volume":"122","author":"Smith","year":"2010","journal-title":"J. Affect. Disord."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s10194-008-0002-5","article-title":"The effect of sodium valproate on chronic daily headache and its subgroups","volume":"9","author":"Yurekli","year":"2008","journal-title":"J. Headache Pain"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.jemermed.2015.02.024","article-title":"Intravenous sodium valproate for acute pediatric headache","volume":"49","author":"Sheridan","year":"2015","journal-title":"J. Emerg. Med."},{"key":"ref_33","first-page":"487","article-title":"Effects of fluoxetine on the anticonvulsant action of valproate and ethosuximide in mouse model of myoclonic convulsions","volume":"19","author":"Borowicz","year":"2012","journal-title":"Ann. Agric. Environ. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.seizure.2014.06.001","article-title":"Pharmacodynamic and pharmacokinetic interactions of perampanel and other antiepileptic drugs in a rat amygdala kindling model","volume":"23","author":"Wu","year":"2014","journal-title":"Seizure"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1212\/WNL.0000000000001772","article-title":"Dose-dependent teratogenicity of valproate in mono- and polytherapy: An observational study","volume":"85","author":"Tomson","year":"2015","journal-title":"Neurology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2574","DOI":"10.1007\/s11064-016-1969-y","article-title":"Prenatal exposure to histone deacetylase inhibitors affects gene expression of autism-related molecules and delays neuronal maturation","volume":"41","author":"Kawanai","year":"2016","journal-title":"Neurochem. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.seizure.2017.01.003","article-title":"Intrauterine valproate exposure is associated with alterations in hippocampal cell numbers and folate metabolism in a rat model of valproate teratogenicity","volume":"46","author":"Semmler","year":"2017","journal-title":"Seizure"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"95","DOI":"10.2174\/1874467210902010095","article-title":"Biochemical, molecular and epigenetic mechanisms of valproic acid neuroprotection","volume":"2","author":"Monti","year":"2009","journal-title":"Curr. Mol. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2781","DOI":"10.1084\/jem.20081588","article-title":"Valproic acid inhibits A\u03b2 production, neuritic plaque formation, and behavioral deficits in Alzheimer\u2019s disease mouse models","volume":"205","author":"Qing","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s12031-011-9644-x","article-title":"Effect of sodium valproate administration on brain neprilysin expression and memory in rats","volume":"46","author":"Nalivaeva","year":"2012","journal-title":"J. Mol. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1007\/s12640-009-9090-5","article-title":"Valproic acid is neuroprotective in the rotenone rat model of Parkinson\u2019s disease: Involvement of alpha-synuclein","volume":"17","author":"Monti","year":"2010","journal-title":"Neurotox. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.pbb.2009.08.001","article-title":"Valproate ameliorates the survival and the motor performance in a transgenic mouse model of Huntington\u2019s disease","volume":"94","author":"Geisz","year":"2009","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3179","DOI":"10.1111\/j.1460-9568.2004.03765.x","article-title":"Benefit of valproic acid in suppressing disease progression of ALS model mice","volume":"11","author":"Sugai","year":"2004","journal-title":"Eur. J. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Dash, P.K., Orsi, S.A., Zhang, M., Grill, R.J., Pati, S., Zhao, J., and Moore, A.N. (2010). Valproate administered after traumatic brain injury provides neuroprotection and improves cognitive function in rats. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011383"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s10059-011-0019-5","article-title":"A critical time window for the survival of neural progenitor cells by HDAC inhibitors in the hippocampus","volume":"31","author":"Kim","year":"2011","journal-title":"Mol. Cells"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1038\/mp.2015.3","article-title":"Valproic acid enhances neuronal differentiation of sympathoadrenal progenitor cells","volume":"20","author":"Qin","year":"2015","journal-title":"Mol. Psychiatry"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/j.stemcr.2015.10.012","article-title":"Reduced adult hippocampal neurogenesis and cognitive impairments following prenatal treatment of the antiepileptic drug valproic acid","volume":"8","author":"Juliandi","year":"2015","journal-title":"Stem Cell Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.pnpbp.2010.09.019","article-title":"Effects of mood stabilizers on adult dentate gyrus-derived neural precursor cells","volume":"35","author":"Boku","year":"2011","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1007\/s11064-015-1618-x","article-title":"Valproic acid arrests proliferation but promotes neuronal differentiation of adult spinal NSPCs from SCI rats","volume":"40","author":"Chu","year":"2015","journal-title":"Neurochem. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s11064-011-0607-y","article-title":"L-type calcium channel mediates anticonvulsant effect of cannabinoids in acute and chronic murine models of seizure","volume":"37","author":"Naderi","year":"2012","journal-title":"Neurochem. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejphar.2013.05.040","article-title":"The role of \u03b1\u2082-adrenoceptors in the anti-convulsant effects of cannabinoids on pentylenetetrazole-induced seizure threshold in mice","volume":"15","author":"Shafaroodi","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1111\/j.1528-1167.2009.02098.x","article-title":"The effects of intracerebroventricular AM-251, a CB1-receptor antagonist, and ACEA, a CB1-receptor agonist, on penicillin-induced epileptiform activity in rats","volume":"50","author":"Kozan","year":"2009","journal-title":"Epilepsia"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/cns.12075","article-title":"The role of CB1-receptors in the proconvulsant effect of leptin on penicillin-induced epileptiform activity in rats","volume":"19","author":"Arslan","year":"2013","journal-title":"CNS Neurosci. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.npep.2014.09.003","article-title":"The interaction between ghrelin and cannabinoid systems in penicillin-induced epileptiform activity in rats","volume":"48","author":"Arslan","year":"2014","journal-title":"Neuropeptides"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3104","DOI":"10.1172\/JCI25509","article-title":"Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects","volume":"115","author":"Jiang","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"379","DOI":"10.3389\/fncel.2015.00379","article-title":"Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain","volume":"9","author":"Rivera","year":"2015","journal-title":"Front. Cell. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e1118177","DOI":"10.1080\/23262133.2015.1118177","article-title":"Cannabinoid receptor signaling induces proliferation but not neurogenesis in the mouse olfactory epithelium","volume":"3","author":"Hutch","year":"2016","journal-title":"Neurogenesis"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.pharep.2014.12.002","article-title":"Long-term disease-modifying effect of the endocannabinoid agonist WIN55,212-2 in a rat model of audiogenic epilepsy","volume":"67","author":"Vinogradova","year":"2015","journal-title":"Pharmacol. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.aanat.2016.04.029","article-title":"Kaempferia parviflora extract ameliorates the cognitive impairments and the reduction in cell proliferation induced by valproic acid treatment in rats","volume":"206","author":"Welbat","year":"2016","journal-title":"Ann. Anat."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Welbat, J.U., Sirichoat, A., Chaijaroonkhanarak, W., Prachaney, P., Pannangrong, W., Pakdeechote, P., Sripanidkulchai, B., and Wigmore, P. (2016). Asiatic acid prevents the deleterious effects of valproic acid on cognition and hippocampal cell proliferation and survival. Nutrients, 8.","DOI":"10.3390\/nu8050303"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Bhaskaran, M.D., and Smith, B.N. (2010). Cannabinoid-mediated inhibition of recurrent excitatory circuitry in the dentate gyrus in a mouse model of temporal lobe epilepsy. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010683"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.expneurol.2012.08.022","article-title":"Rapid epileptogenesis in the mouse pilocarpine model: Video-EEG, pharmacokinetic and histopathological characterization","volume":"238","author":"Mazzuferri","year":"2012","journal-title":"Exp. Neurol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/0006-8993(72)90268-5","article-title":"Epileptiform activity and neural plasticity in limbic structures","volume":"47","author":"Racine","year":"1972","journal-title":"Brain Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.jneumeth.2008.04.019","article-title":"The pilocarpine model of temporal lobe epilepsy","volume":"172","author":"Curia","year":"2008","journal-title":"J. Neurosci. Methods"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1002\/glia.23008","article-title":"Microglia are less pro-inflammatory than myeloid infiltrates in the hippocampus of mice exposed to status epilepticus","volume":"64","author":"Vinet","year":"2016","journal-title":"Glia"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1002\/ar.1090940210","article-title":"Estimation of nuclear population from microtome sections","volume":"94","author":"Abercrombie","year":"1946","journal-title":"Anat. 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