{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T22:15:29Z","timestamp":1781475329082,"version":"3.54.1"},"reference-count":66,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T00:00:00Z","timestamp":1615161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp; Molecular Tox"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Past assassinations and terrorist attacks demonstrate the need for a more effective antidote against nerve agents and other organophosphates (OP) that cause brain damage through inhibition of acetylcholinesterase (AChE). Our lab has invented a platform of phenoxyalkyl pyridinium oximes (US patent 9,277,937) that demonstrate the ability to cross the blood\u2013brain barrier in in vivo rat tests with a sarin surrogate nitrophenyl isopropyl methylphosphonate (NIMP) and provide evidence of brain penetration by reducing cessation time of seizure\u2010like behaviors, accumulation of glial fibrillary acidic protein (GFAP), and hippocampal neuropathology, as opposed to\u00a0the currently approved oxime, 2\u2010pyridine aldoxime methyl chloride (2\u2010PAM). Using two of the novel oximes (Oximes 1 and 20), this project examined whether gene expression changes might help explain this protection. Expression changes in the piriform cortex were examined using polymerase chain reaction arrays for inflammatory cytokines and receptors. The hippocampus was examined via quantitative polymerase chain reaction for the expression of immediate\u2010early genes involved in brain repair (<jats:italic>Bdnf<\/jats:italic>), increasing neurotoxicity (<jats:italic>Fos<\/jats:italic>), and apoptosis control (<jats:italic>Jdp2, Bcl2l1, Bcl2l11<\/jats:italic>). In the piriform cortex, NIMP significantly stimulated expression for the macrophage inflammatory proteins CCL4, IL\u20101A, and IL\u20101B. Oxime 20 by itself elicited the most changes. When it was given therapeutically post\u2010NIMP, the largest change occurred: a 310\u2010fold repression of the inflammatory cytokine, CCL12. In the hippocampus, NIMP increased the expression of the neurotoxicity marker <jats:italic>Fos<\/jats:italic> and decreased the expression of neuroprotective <jats:italic>Bdnf<\/jats:italic> and antiapoptotic <jats:italic>Bcl2l1<\/jats:italic>. Compared with 2\u2010PAM, Oxime 20 stimulated <jats:italic>Bcl2l1<\/jats:italic> expression more and returned expression closer to the vehicle control values.<\/jats:p>","DOI":"10.1002\/jbt.22755","type":"journal-article","created":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T08:58:44Z","timestamp":1615193924000},"page":"1-10","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of novel brain\u2010penetrating oxime acetylcholinesterase reactivators on sarin surrogate\u2010induced changes in rat brain gene expression"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6767-979X","authenticated-orcid":false,"given":"Mary E.","family":"Dail","sequence":"first","affiliation":[{"name":"Department of Comparative Biomedical Sciences, Center for Environmental Health Sciences Mississippi State University, College of Veterinary Medicine  Mississippi State United States USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan L. M.","family":"Brino","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedical Sciences, Center for Environmental Health Sciences Mississippi State University, College of Veterinary Medicine  Mississippi State United States USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7826-7042","authenticated-orcid":false,"given":"Janice E.","family":"Chambers","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedical Sciences, Center for Environmental Health Sciences Mississippi State University, College of Veterinary Medicine  Mississippi State United States USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-7634(96)00050-4"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0234967"},{"key":"e_1_2_9_4_1","volume-title":"The 13th Element: The Sordid Tale of Murder, Fire, and Phosphorus","author":"Emsley J.","year":"2000"},{"key":"e_1_2_9_5_1","first-page":"115","volume":"26","author":"Tu A. T.","year":"2014","journal-title":"Forensic Sci. Rev"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11419-017-0376-7"},{"key":"e_1_2_9_7_1","unstructured":"L.Loveluck Autopsies point to the use of sarin. The Washington Post 04\/07\/2017.High Beam Research2017.https:\/\/www.washingtonpost.com\/world\/global-watchdog-confirms-nerve-agent-used-in-april-attack-on-syrian-civilians\/2017\/06\/30\/aa316cb6-5c16-11e7-aa69-3964a7d55207_story.html(accessed: January 2018)."},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.359.6382.1314"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010818-021842"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1024960819430"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13181-017-0636-2"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-006-9123-1"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfs013"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2012.10.017"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfy212"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfz060"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2012.02.002"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-8-83"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2015.04.015"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2015.00027"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(02)00158-4"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbior.2016.05.001"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/340474a0"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-016-4498-0"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-005-9023-5"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-017-9815-9"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.9.e45"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2003.10.019"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21029"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2014.03.004"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2006.01657.x"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.23.14363"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.1.99"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.04272.x"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2015.08.013"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-8-14"},{"key":"e_1_2_9_38_1","doi-asserted-by":"crossref","first-page":"7151","DOI":"10.4049\/jimmunol.151.12.7151","volume":"151","author":"Doherty T. M.","year":"1993","journal-title":"J. Immunol"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23053"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201343301"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20989"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2015.08.001"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1059157"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(2002010)32:10<2874::AID-IMMU2874>3.0.CO;2-4"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603107103"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.7.4634"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0316-6"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458512463766"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-4-12"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2010.05.010"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2008-14203"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2014.120"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(00)00399-7"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/0169-328X(92)90051-C"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/363166a0"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03200.x"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.034"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01795.x"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2791"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2330"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2016.07.004"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2018.04.002"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.19.3.1720"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.05.042"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2004-6-1-r9"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2003.11.015"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-004-0565-0"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.22755","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.22755","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.22755","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T07:41:23Z","timestamp":1692690083000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.22755"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,8]]},"references-count":66,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1002\/jbt.22755"],"URL":"https:\/\/doi.org\/10.1002\/jbt.22755","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,8]]},"assertion":[{"value":"2020-11-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}