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The influence of SIM on hydrogen sulphide (H<jats:sub>2<\/jats:sub>S), nitric oxide (NO), reactive aldehydes and brain\u2010derived neurotrophic factor\/tyrosine receptor kinase B (BDNF\u2010TrkB) signalling was also investigated. Kindling and cognitive impairments in mice were induced by 12 ip injections of PTZ (35\u00a0mg\/kg) once every alternate day. The levels of reactive aldehydes and nitrite were increased while H<jats:sub>2<\/jats:sub>S was decreased in PTZ\u2010treated mice. These results were accompanied by a reduction in the gene expression of aldehyde dehydrogenase 2, cystathionine \u03b2\u2010synthase, BDNF and TrkB. In PTZ\u2010kindled mice, a rise in brain inducible nitric oxide synthase protein expression associated with histopathological changes was observed. SIM administration (1, 5 and 10\u00a0mg\/kg, daily orally) along with alternate day of PTZ (35\u00a0mg\/kg) resulted in a decrease in PTZ\u2010induced kindling with a dose\u2010dependent improvement in cognitive function. SIM (10\u00a0mg\/kg) prevented, to variable extent, the disturbances associated with PTZ\u2010kindled mice with cortical, cerebellar and hippocampal structural improvement. These results suggested that SIM triggers multiple mechanisms that improve cognitive function in PTZ\u2010kindled mice through modulation of oxidative stress, H<jats:sub>2<\/jats:sub>S, NO and BDNF\u2010TrkB signalling pathway.<\/jats:p>","DOI":"10.1111\/bcpt.13457","type":"journal-article","created":{"date-parts":[[2020,6,20]],"date-time":"2020-06-20T20:38:35Z","timestamp":1592685515000},"page":"461-476","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Involvement of H<sub>2<\/sub>S, NO and BDNF\u2010TrkB signalling pathway in the protective effects of simvastatin against pentylenetetrazole\u2010induced kindling and cognitive impairments in mice"],"prefix":"10.1111","volume":"127","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0566-3033","authenticated-orcid":false,"given":"Marwa A.","family":"Ahmed","sequence":"first","affiliation":[{"name":"Department of Pharmacology Faculty of Medicine Assiut University Assiut Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esam O.","family":"Kamel","sequence":"additional","affiliation":[{"name":"Department of Medical Histology and Cell Biology Faculty of Medicine Al\u2010Azhar University Assiut Branch Assiut Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2003.11.004"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00377"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2018.11.038"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-03-01046.1997"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0098-2997(03)00024-4"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1353-8020(13)70019-1"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2015.1"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-010-0685-1"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706680"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2005.09.057"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2015.05.018"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7RA11491E"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2018.03.001"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2010.10.054"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-017-1964-4"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0119478"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.2183\/pjab.86.484"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2009.01.002"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2010-101653"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1592\/phco.23.6.726.32184"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2010.11.067"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13256-016-0877-8"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13059"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0013-4694(72)90178-2"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.10.056"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2013.01.007"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(79)90738-3"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(71)90116-3"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.4236\/abc.2012.24044"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1006\/niox.2000.0319"},{"key":"e_1_2_7_32_1","volume-title":"Theory and Practice of Histological Techniques","author":"Bancroft JD","year":"2008"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1139\/f96-174"},{"key":"e_1_2_7_34_1","first-page":"339","volume-title":"Fish Gills as a Monitor of Sublethal and Chronic Effects of Pollution. 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