{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T02:37:11Z","timestamp":1780108631284,"version":"3.54.0"},"reference-count":53,"publisher":"IMR Press","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Integr. Neurosci."],"abstract":"<jats:p>Systemic kainic acid administration has been used to induce experimental temporal lobe epilepsy in rats. The aim was to evaluate the neuroprotective effect of rosemary extract (40% Carnosic acid) against kainic acid-induced neurotoxicity in hippocampus and impaired learning and memory. Subjects received a single dose of kainic acid (9.5 mg\/kg) intraperitoneally, were observed for two hours, and scored from 0 (for normal, no convulsion) to five (for continuous generalized limbic seizures). Rosemary extract (100 mg\/kg, orally) was administered daily for 23 days, starting a week before kainic acid injection. Neuronal degeneration in hippocampus was demonstrated by using Fluoro-Jade B immunofluorescence. The number of pyramidal cells in hippocampus was evaluated by Nissl staining. Also, the Morris water maze and shuttle box were used to assess spatial memory and passive avoidance learning, respectively. Results revealed that, after treatment with rosemary extract, neuronal loss in CA1 decreased significantly in subjects in the kainic acid + rosemary extract group. Morris water navigation task results revealed that spatial memory impairment decreased in subjects in the kainic acid + rosemary extract group. Furthermore, results in shuttle box testing showed that passive avoidance learning impairment significantly improved for subjects in the kainic acid + rosemary extract group. These results suggest that rosemary extract improves spatial and working memory deficits and also, due to its antioxidant activities, neuronal degeneration induced by the toxicity of kainic acid in rat hippocampus.<\/jats:p>","DOI":"10.31083\/jin-170035","type":"journal-article","created":{"date-parts":[[2018,9,19]],"date-time":"2018-09-19T02:59:52Z","timestamp":1537325992000},"source":"Crossref","is-referenced-by-count":5,"title":["The role of rosemary extract in degeneration of hippocampal neurons induced by kainic acid in the rat: A behavioral and histochemical approach"],"prefix":"10.31083","volume":"17","author":[{"given":"Elahe","family":"Naderali","sequence":"first","affiliation":[{"name":"Anatomy Department, Medical school, Iran University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farnaz","family":"Nikbakht","sequence":"first","affiliation":[{"name":"Physiology Department, Medical School, Iran University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sattar Norouzi","family":"Ofogh","sequence":"first","affiliation":[{"name":"Neuroscience Department, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Homa","family":"Rasoolijazi","sequence":"first","affiliation":[{"name":"Anatomy Department, Medical school, Iran University of Medical Sciences, Tehran, Iran"},{"name":"Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2018,1,15]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Kwan P, Brodie MJ ( 2006) Refractory epilepsy: mechanisms and solutions. Expert Review of Neurotherapeutics 6( 3), 397-406.","DOI":"10.1586\/14737175.6.3.397"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Stafstrom CE, Thompson JL, Holmes GL ( 1992) Kainic acid seizures in the developing brain: status epilepticus and spontaneous recurrent seizures. Developmental Brain Research 65( 2), 227-236.","DOI":"10.1016\/0165-3806(92)90184-X"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Lewerenz J, Maher P ( 2015) Chronic Glutamate Toxicity in Neurodegenerative Diseases--What is the Evidence? Frontiers in Neuroscience 9, 469.","DOI":"10.3389\/fnins.2015.00469"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Ferkany JW, Zaczek R, Coyle JT ( 1982) Kainic acid stimulates excitatory amino acid neurotransmitter release at presynaptic receptors. Nature 298( 5876), 757-759.","DOI":"10.1038\/298757a0"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Sperk G ( 1994) Kainic acid seizures in the rat. Progress in Neurobiology 42( 1), 1-32.","DOI":"10.1016\/0301-0082(94)90019-1"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Sun QJ, Duan RS, Wang AH, Shang W, Zhang T, Zhang XQ, Chi ZF ( 2009) Alterations of NR2B and PSD-95 expression in hippocampus of kainic acid-exposed rats with behavioural deficits. Behavioural Brain Research 201( 2), 292-299.","DOI":"10.1016\/j.bbr.2009.02.027"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Jaako K, Aonurmhelm A, Kalda A, Anier K, Zharkovsky T, Shastin D, Zharkovsky A ( 2011) Repeated citalopram administration counteracts kainic acid-induced spreading of PSA-NCAM-immunoreactive cells and loss of reelin in the adult mouse hippocampus. European Journal of Pharmacology 666( 1-3), 61-71.","DOI":"10.1016\/j.ejphar.2011.05.008"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Hynd MR, Scott HL, Dodd PR ( 2010) Selective loss of NMDA receptor NR1 subunit isoforms in Alzheimer\u2019s disease. Journal of Neurochemistry 89( 1), 240-247.","DOI":"10.1111\/j.1471-4159.2003.02330.x"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Estrada S\u00e1nchez AM, Mej\u00edatoiber J, Massieu L ( 2008) Excitotoxic neuronal death and the pathogenesis of Huntington\u2019s disease. Archives of Medical Research 39( 3), 265-276.","DOI":"10.1016\/j.arcmed.2007.11.011"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Heath PR, Tomkins J, Ince PG, Shaw PJ ( 2002) Quantitative assessment of AMPA receptor mRNA in human spinal motor neurons isolated by laser capture microdissection. Neuroreport 13( 14), 1753-1757.","DOI":"10.1097\/00001756-200210070-00012"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Ginsberg MD ( 2008) Neuroprotection for ischemic stroke: past, present and future. Neuropharmacology 55( 3), 363-389.","DOI":"10.1016\/j.neuropharm.2007.12.007"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Jin YC, Lim CM, Kim SW, Park JY, Seo JS, Han PL, Yoon SH, Lee JK ( 2009) Fluoxetine attenuates kainic acid-induced neuronal cell death in the mouse hippocampus. Journal of Neuroscience Research 84( 7), 108-116.","DOI":"10.1016\/j.brainres.2009.04.053"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Lee J, Kim D, Hong H, Han S, Kim JY ( 2000) Protective effect of etomidate on kainic acid-induced neurotoxicity in rat hippocampus. Neuroscience Letters 286( 3), 179-182.","DOI":"10.1016\/S0304-3940(00)01118-6"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Wang Q, Yu S, Simonyi A, Sun GY, Sun AY ( 2005) Kainic acidmediated excitotoxicity as a model for neurodegeneration. Molecular Neurobiology 31( 1-3), 3-16. &amp;icode=MN:31:1-3","DOI":"10.1385\/MN:31:1-3:003"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"\u017degura B, Dobnik D, Niderl MH, Filipi\u010d M ( 2011) Antioxidant and antigenotoxic effects of rosemary (Rosmarinus officinalis L.) extracts in Salmonella typhimurium TA98 and HepG2 cells. Environmental Toxicology & Pharmacology 32( 2), 296-305.","DOI":"10.1016\/j.etap.2011.06.002"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"\u00d6zcan M ( 1999) Actividad antioxidante de extractos de romero (Rosmarinus officinalis L) en aceites de s\u00e9samo y de oliva: Antioxidant activity of rosemary (Rosmarinus officinalis L.) extracts on natural olive and sesame oils. Grasas Y Aceites 50( 5), 355-358.","DOI":"10.3989\/gya.1999.v50.i5.679"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Doolaege EH, Vossen E, Raes K, De MB, Verh\u00e9 R, Paelinck H, De SS ( 2012) Effect of rosemary extract dose on lipid oxidation, colour stability and antioxidant concentrations, in reduced nitrite liver pates. Meat Science 90( 4), 925-931.","DOI":"10.1016\/j.meatsci.2011.11.034"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Sotelof\u00e9lix JI, Martinezfong D, Muriel P, Santill\u00e1n RL, Castillo D, Yahuaca P ( 2002) Evaluation of the effectiveness of Rosmarinus officinalis (Lamiaceae) in the alleviation of carbon tetrachloride-induced acute hepatotoxicity in the rat. Journal of Ethnopharmacology 81( 2), 145-154.","DOI":"10.1016\/S0378-8741(02)00090-9"},{"key":"ref19","unstructured":"Del CJ, Amiot MJ, Nguyen-The C ( 2000) Antimicrobial effect of rosemary extracts. Journal of Food Protection 63( 10), 1359-1368. <933::AID-JCTB301>3.3.CO;2-311041135235b6a7424dbfb180dc1f2a0941c1a5dhttp%3A%2F%2Fwww.cabdirect.org%2Fabstracts%2F20003015571.htmlhttp:\/\/jfoodprotection.org\/doi\/abs\/10.4315\/0362-028X-63.10.1359"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Amaral GP, de Carvalho NR, Barcelos RP, Dobrachinski F, Portella RL, Da SM, Lugokenski TH, Dias GR, Da LS, Boligon AA ( 2013) Protective action of ethanolic extract of Rosmarinus officinalis L. in gastric ulcer prevention induced by ethanol in rats. Food & Chemical Toxicology 55( 18), 48-55.","DOI":"10.1016\/j.fct.2012.12.038"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Ramadan KS, Khalil OA, Danial EN, Alnahdi HS, Ayaz NO ( 2013) Hypoglycemic and hepatoprotective activity of Rosmarinus officinalis extract in diabetic rats. Journal of Physiology & Biochemistry 69( 4), 779-783.","DOI":"10.1007\/s13105-013-0253-8"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Altinier G, Sosa S, Aquino RP, Mencherini T, Loggia RD, Tubaro A ( 2007) Characterization of Topical Antiinflammatory Compounds in Rosmarinus officinalis L. Journal of Agricultural and Food Chemistry 55( 5), 1718-1723.","DOI":"10.1021\/jf062610+"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Machado DG, Cunha MP, Neis VB, Balen GO, Colla A, Bettio LE, Oliveira A, Pazini FL, Dalmarco JB, Simionatto EL ( 2013) Antidepressant-like effects of fractions, essential oil, carnosol and betulinic acid isolated from Rosmarinus officinalis L. Food Chemistry 136( 2), 999-1005.","DOI":"10.1016\/j.foodchem.2012.09.028"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Racine RJ ( 1972) Modification of seizure activity by electrical stimulation: I. After-discharge threshold. Electroencephalography & Clinical Neurophysiology 32( 3), 269-279.","DOI":"10.1016\/0013-4694(72)90176-9"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Silva RH, Felicio LF, Frussafilho R ( 1999) Ganglioside GM1 attenuates scopolamine-induced amnesia in rats and mice. Psychopharmacology 141( 2), 111-117.","DOI":"10.1007\/s002130050814"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"Schmued LC, Hopkins KJ ( 2000) Fluoro-Jade: novel fluorochromes for detecting toxicant-induced neuronal degeneration. Toxicologic Pathology 28( 1), 91-99.","DOI":"10.1177\/019262330002800111"},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"Gurbanova AA, Aker RG, Sirvanci S, Demiralp T, Onat FY ( 2008) Intra-amygdaloid injection of kainic acid in rats with genetic absence epilepsy: the relationship of typical absence epilepsy and temporal lobe epilepsy. Journal of Neuroscience the Official Journal of the Society for Neuroscience 28( 31), 7828-7836.","DOI":"10.1523\/JNEUROSCI.1097-08.2008"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"Sperk G, Lassmann H, Baran H, Kish SJ, Seitelberger F, Hornykiewicz O ( 1983) Kainic acid induced seizures: neurochemical and histopathological changes. Neuroscience 10( 4), 1301-1315.","DOI":"10.1016\/0306-4522(83)90113-6"},{"key":"ref29","doi-asserted-by":"crossref","unstructured":"Inostroza M, Cid E, Brotonsmas J, Gal B, Aivar P, Uzcategui YG, Sandi C, Prida LMDL ( 2011) Hippocampal-Dependent Spatial Memory in the Water Maze is Preserved in an Experimental Model of Temporal Lobe Epilepsy in Rats. Plos One 6( 7), e22372.","DOI":"10.1371\/journal.pone.0022372"},{"key":"ref30","doi-asserted-by":"crossref","unstructured":"M\u00fcller CJ, Gr\u00f6ticke I, Bankstahl M, L\u00f6scher W ( 2009) Behavioral and cognitive alterations, spontaneous seizures, and neuropathology developing after a pilocarpine-induced status epilepticus in C57BL\/6 mice. Experimental Neurology 219( 1), 284-297.","DOI":"10.1016\/j.expneurol.2009.05.035"},{"key":"ref31","doi-asserted-by":"crossref","unstructured":"Kim DH, Yoon BH, Jung WY, Kim JM, Park SJ, Dong HP, Huh Y, Chan P, Cheong JH, Lee KT ( 2010) Sinapic acid attenuates kainic acidinduced hippocampal neuronal damage in mice. Neuropharmacology 59( 1, 2), 20-30.","DOI":"10.1016\/j.neuropharm.2010.03.012"},{"key":"ref32","doi-asserted-by":"crossref","unstructured":"Stubleyweatherly L, Harding JW, Wright JW ( 1996) Effects of discrete kainic acid-induced hippocampal lesions on spatial and contextual learning and memory in rats. Brain Research 716( 1, 2), 29-38.","DOI":"10.1016\/0006-8993(95)01589-2"},{"key":"ref33","doi-asserted-by":"crossref","unstructured":"Pearson JN, Schulz KM, Patel M ( 2014) Specific alterations in the performance of learning and memory tasks in models of chemoconvulsantinduced status epilepticus. Epilepsy Research 108( 6), 1032-1040.","DOI":"10.1016\/j.eplepsyres.2014.04.003"},{"key":"ref34","doi-asserted-by":"crossref","unstructured":"Bozzi Y, Vallone D, Borrelli E ( 2000) Neuroprotective role of dopamine against hippocampal cell death. Journal of Neuroscience the Official Journal of the Society for Neuroscience 20( 22), 8643-8649.","DOI":"10.1523\/JNEUROSCI.20-22-08643.2000"},{"key":"ref35","doi-asserted-by":"crossref","unstructured":"Tripathi PP, Santorufo G, Brilli E, Borrelli E, Bozzi Y ( 2010) Kainic acid-induced seizures activate GSK-3b in the hippocampus of D2R-\/- mice. Neuroreport 21( 12), 846-850.","DOI":"10.1097\/WNR.0b013e32833d5891"},{"key":"ref36","doi-asserted-by":"crossref","unstructured":"Yoshihara Y, Onodera H, Iinuma K, Itoyama Y ( 2003) Abnormal kainic acid receptor density and reduced seizure susceptibility in dystrophindeficient mdx mice. Neuroscience 117( 2), 391-395.","DOI":"10.1016\/S0306-4522(02)00876-X"},{"key":"ref37","doi-asserted-by":"crossref","unstructured":"Leutgeb S, Leutgeb JK, Barnes CA, Moser EI, Mcnaughton BL, Moser MB ( 2005) Independent codes for spatial and episodic memory in hippocampal neuronal ensembles. Science 309( 5734), 619-623.","DOI":"10.1126\/science.1114037"},{"key":"ref38","unstructured":"Riljak V, Milotov\u00e1 M, Jandov\u00e1 K, Langmeier M, Maresov\u00e1 D, Pokorn\u00fd J, Trojan S ( 2005) Repeated kainic acid administration and hippocampal neuronal degeneration. Prague Medical Report 106( 1), 75-78. 16007912a37f99c71cfbc74bae64a5feaf5d8714http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F16007912http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/16007912"},{"key":"ref39","doi-asserted-by":"crossref","unstructured":"Baba S, Onga K, Kakizawa S, Ohyama K, Yasuda K, Otsubo H, Scott BW, Burnham MI, Matsuo T, Nagata I ( 2016) Involvement of the neuronal phosphotyrosine signal adaptor N-Shc in kainic acid-induced epileptiform activity. Scientific Reports 6, 27511.","DOI":"10.1038\/srep27511"},{"key":"ref40","doi-asserted-by":"crossref","unstructured":"Liu G, Kotloski RJ, Mcnamara JO ( 2014) Antiseizure effects of TrkB kinase inhibition. Epilepsia 55( 8), 1264-1273.","DOI":"10.1111\/epi.12671"},{"key":"ref41","doi-asserted-by":"crossref","unstructured":"Cassel A, Morris R, Koutroumanidis M, Kopelman M ( 2016) Forgetting in temporal lobe epilepsy: When does it become accelerated? Cortex 78, 70-84.","DOI":"10.1016\/j.cortex.2016.02.005"},{"key":"ref42","doi-asserted-by":"crossref","unstructured":"Gascoigne MB, Smith ML, Barton B, Webster R, Gill D, Lah S ( 2014) Accelerated long-term forgetting in children with temporal lobe epilepsy. Neuropsychologia 59( 1), 93-102.","DOI":"10.1016\/j.neuropsychologia.2014.04.012"},{"key":"ref43","doi-asserted-by":"crossref","unstructured":"Halliwell B ( 2006) Oxidative stress and neurodegeneration: where are we now? Journal of Neurochemistry 97( 6), 1634-1658.","DOI":"10.1111\/j.1471-4159.2006.03907.x"},{"key":"ref44","doi-asserted-by":"crossref","unstructured":"Liang LP, Beaudoin ME, Fritz MJ, Fulton R, Patel M ( 2007) Kainateinduced seizures, oxidative stress and neuronal loss in aging rats. Neuroscience 147( 4), 1114-1118.","DOI":"10.1016\/j.neuroscience.2007.03.026"},{"key":"ref45","doi-asserted-by":"crossref","unstructured":"Mishra V, Shuai B, Kodali M, Shetty GA, Hattiangady B, Rao X, Shetty AK ( 2015) Resveratrol Treatment after Status Epilepticus Restrains Neurodegeneration and Abnormal Neurogenesis with Suppression of Oxidative Stress and Inflammation. Scientific Reports 5, 17807.","DOI":"10.1038\/srep17807"},{"key":"ref46","doi-asserted-by":"crossref","unstructured":"Chan SL, Liu D, Kyriazis GA, Bagsiyao P, Ouyang X, Mattson MP ( 2006) Mitochondrial uncoupling protein-4 regulates calcium homeostasis and sensitivity to store depletion-induced apoptosis in neural cells. Journal of Biological Chemistry 281( 49), 37391-37403.","DOI":"10.1074\/jbc.M605552200"},{"key":"ref47","doi-asserted-by":"crossref","unstructured":"Ermak G, Davies KJ ( 2002) Calcium and oxidative stress: from cell signaling to cell death. Molecular Immunology 38( 10), 713-721.","DOI":"10.1016\/S0161-5890(01)00108-0"},{"key":"ref48","doi-asserted-by":"crossref","unstructured":"George S, Chaturvedi P ( 2008) Protective role of Ocimum canum plant extract in alcohol-induced oxidative stress in albino rats. British Journal of Biomedical Science 65( 2), 80-85.","DOI":"10.1080\/09674845.2008.11732802"},{"key":"ref49","doi-asserted-by":"crossref","unstructured":"Yoshioka S, Hamada A, Jobu K, Yokota J, Onogawa M, Kyotani S, Miyamura M, Saibara T, Onishi S, Nishioka Y ( 2010) Effects of Eriobotrya japonica seed extract on oxidative stress in rats with non-steatohepatitis. Journal of Pharmacy & Pharmacology 62( 2), 241-246.","DOI":"10.1211\/jpp.62.02.0012"},{"key":"ref50","doi-asserted-by":"crossref","unstructured":"Hritcu L, Noumedem JA, Cioanca O, Hancianu M, Kuete V, Mihasan M ( 2014) Methanolic extract of Piper nigrum fruits improves memory impairment by decreasing brain oxidative stress in amyloid beta(1-42) rat model of Alzheimer\u2019s disease. Cellular & Molecular Neurobiology 34( 3), 437-449.","DOI":"10.1007\/s10571-014-0028-y"},{"key":"ref51","doi-asserted-by":"crossref","unstructured":"Ra\u0161kovi\u0107 A, Milanovi\u0107 I, Pavlovi\u0107 N, T \u0106, Vukmirovi\u0107 S, Mikov M ( 2014) Antioxidant activity of rosemary (Rosmarinus officinalis L.) essential oil and its hepatoprotective potential. BMC Complementary and Alternative Medicine 14( 1), 225.","DOI":"10.1186\/1472-6882-14-225"},{"key":"ref52","unstructured":"Azad N, Rasoolijazi H, Joghataie MT, Soleimani S ( 2011) Neuroprotective Effects of Carnosic Acid in an Experimental Model of Alzheimer\u2019s Disease in Rats. Cell Journal 13( 1), 39-44."},{"key":"ref53","doi-asserted-by":"crossref","unstructured":"Rasoolijazi H, Azad N, Joghataei MT, Kerdari M, Nikbakht F, Soleimani M ( 2013) The protective role of carnosic acid against beta-amyloid toxicity in rats. 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