{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T06:51:34Z","timestamp":1771829494535,"version":"3.50.1"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Institute of Allergy and Infectious Diseases\/National Institutes of Health","award":["Interagency Agreement number AOD22011-001-00000"],"award-info":[{"award-number":["Interagency Agreement number AOD22011-001-00000"]}]},{"name":"National Institute of Allergy and Infectious Diseases\/National Institutes of Health","award":["Interagency Agreement number AOD22011-001-00000"],"award-info":[{"award-number":["Interagency Agreement number AOD22011-001-00000"]}]},{"name":"National Institute of Allergy and Infectious Diseases\/National Institutes of Health","award":["Interagency Agreement number AOD22011-001-00000"],"award-info":[{"award-number":["Interagency Agreement number AOD22011-001-00000"]}]},{"name":"National Institute of Allergy and Infectious Diseases\/National Institutes of Health","award":["Interagency Agreement number AOD22011-001-00000"],"award-info":[{"award-number":["Interagency Agreement number AOD22011-001-00000"]}]},{"DOI":"10.13039\/100009913","name":"Naval Medical Center San Diego","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009913","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurotox Res"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recently a novel genetically modified mouse strain with serum carboxylesterase knocked-out and the human acetylcholinesterase gene knocked-in (KIKO) was created to simulate human responses to nerve agent (NA) exposure and its standard medical treatment. A<jats:sub>1<\/jats:sub> adenosine receptor (A<jats:sub>1<\/jats:sub>AR) agonist N-bicyclo-(2.2.1)-hept-2-yl-5'-chloro-5'-deoxyadenosine (ENBA) alone is a potent anticonvulsant and neuroprotectant (A\/N) in both rat and KIKO mouse soman (GD) seizure models. In this study we utilized the KIKO mouse to evaluate further the basic pharmacologic A\/N effects of ENBA as an adjunct to standard NA medical treatments (i.e., atropine sulfate, pralidoxime chloride [2-PAM], and midazolam). Male mice, implanted with cortical electroencephalographic (EEG) electrodes, were pretreated with asoxime (HI-6) and exposed to an epileptogenic dose of GD (33\u00a0\u00b5g\/kg, s.c.) or saline (sham exposure) and then treated 15\u00a0min after seizure onset with ENBA at 15\u00a0mg\/kg, i.p. (a minimum efficacy dose in suppressing NA-induced seizure) alone or as an adjunct to standard medical treatments. We collected EEG activity, seizure suppression outcomes, daily body temperature and weight, heart rate, toxic signs, neuropathology, and lethality data for up to 14\u00a0days. Without ENBA, death from NA exposure was 45%, while with ENBA, either alone or in combination with midazolam, the survival improved to 80% and 90%, respectively. Additionally, seizure was suppressed quickly and permanently, toxic signs, hypothermia, and bradycardia recovered by 48\u00a0h, and no neuropathology was evident. Our findings confirmed that ENBA is a potent A\/N adjunct for delayed medical treatments of NA exposure.<\/jats:p>","DOI":"10.1007\/s12640-024-00717-z","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T05:02:19Z","timestamp":1725426139000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacology of Adenosine A1 Receptor Agonist in a Humanized Esterase Mouse Seizure Model Following Soman Intoxication"],"prefix":"10.1007","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5252-9198","authenticated-orcid":false,"given":"Tsung-Ming","family":"Shih","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9253-8738","authenticated-orcid":false,"given":"Crystal","family":"Munoz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cindy","family":"Acon-Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zora-Maya","family":"Keith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,9,4]]},"reference":[{"key":"717_CR1","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.compbiolchem.2018.04.017","volume":"75","author":"A Beste","year":"2018","unstructured":"Beste A, Taylora DE, Shih T-M, Thomas TP (2018) Mechanisms of acetylcholinesterase protection against sarin and soman by adenosine A1 receptor agonist N6-cyclopentyladenosine. Comput Biol Chem 75:74\u201381. https:\/\/doi.org\/10.1016\/j.compbiolchem.2018.04.017","journal-title":"Comput Biol Chem"},{"key":"717_CR2","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.neuropharm.2015.08.046","volume":"104","author":"D Boison","year":"2016","unstructured":"Boison D (2016) Adenosinergic signaling in epilepsy. Neuropharmacology 104:131\u2013139. https:\/\/doi.org\/10.1016\/j.neuropharm.2015.08.046","journal-title":"Neuropharmacology"},{"issue":"3","key":"717_CR3","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1152\/physrev.00049.2017","volume":"98","author":"PA Borea","year":"2018","unstructured":"Borea PA, Gessi S, Merighi S, Vincenzi F, Varani K (2018) Pharmacology of adenosine receptors: the state of the art. Physiol Rev 98(3):1591\u20131625. https:\/\/doi.org\/10.1152\/physrev.00049.2017","journal-title":"Physiol Rev"},{"issue":"11","key":"717_CR4","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1007\/s00204-002-0395-x","volume":"76","author":"TJ Bueters","year":"2002","unstructured":"Bueters TJ, Groen B, Danhof M, IJzerman AP, van Helden HP (2002) Therapeutic efficacy of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) against organophosphate intoxication. Arch Toxicol 76(11):650\u2013656. https:\/\/doi.org\/10.1007\/s00204-002-0395-x","journal-title":"Arch Toxicol"},{"key":"717_CR5","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.neuropharm.2016.11.026","volume":"114","author":"JL Carlin","year":"2017","unstructured":"Carlin JL, Jain S, Gizewski E, Wan TC, Tosh DK, Xiao C, Auchampach JA, Jacobson KA, Gavrilova O, Reitman ML (2017) Hypothermia in mouse is caused by adenosine A1 and A3 receptor agonists and AMP via three distinct mechanisms. Neuropharmacology 114:101\u2013113. https:\/\/doi.org\/10.1016\/j.neuropharm.2016.11.026","journal-title":"Neuropharmacology"},{"key":"717_CR6","unstructured":"Cerasoli D, Matson E, Barry T, DeBus S, Hall N, Hamilton T, Zimmerman D, McDonough J, Shih T-M, Anderson D,  Cadieux CL (2019) A novel genetically modified mouse model for evaluating nerve agent countermeasures. In: Proceedings of the 3rd International CBRNE Research & Innovation Conference, Nantes, France, 20\u201323 May 2019"},{"issue":"7218","key":"717_CR7","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1136\/bmj.319.7218.1154","volume":"319","author":"F Charatan","year":"1999","unstructured":"Charatan F (1999) Nerve gas antidote a possible cause of Gulf war illness. BMJ 319(7218):1154. https:\/\/doi.org\/10.1136\/bmj.319.7218.1154","journal-title":"BMJ"},{"key":"717_CR8","doi-asserted-by":"publisher","first-page":"119","DOI":"10.3389\/fneur.2019.00119","volume":"10","author":"F Chen","year":"2019","unstructured":"Chen F, He X, Luan G, Li T (2019) Role of DNA methylation and adenosine in ketogenic diet for pharmacoresistant epilepsy: focus on epileptogenesis and associated comorbidities. Front Neural 10:119. https:\/\/doi.org\/10.3389\/fneur.2019.00119","journal-title":"Front Neural"},{"issue":"5","key":"717_CR9","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.siny.2010.02.002","volume":"15","author":"MR Cilio","year":"2010","unstructured":"Cilio MR, Ferriero DM (2010) Synergistic neuroprotective therapies with hypothermia. Semin Fetal Neonatal Med 15(5):293\u2013298. https:\/\/doi.org\/10.1016\/j.siny.2010.02.002","journal-title":"Semin Fetal Neonatal Med"},{"key":"717_CR10","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/s11302-005-0649-1","volume":"1","author":"RA Cunha","year":"2005","unstructured":"Cunha RA (2005) Neuroprotection by adenosine in the brain: from A(1) receptor activation to A (2A) receptor blockade. Purinergic Signaling 1:111\u2013134. https:\/\/doi.org\/10.1007\/s11302-005-0649-1","journal-title":"Purinergic Signaling"},{"key":"717_CR11","unstructured":"DeBus SJ, Matson EM, Barry TB, Cadieux CL (2019) Characterization of nerve agent intoxication in a novel genetically modified mouse model. In Proceedings of the 3rd International CBRNE Research & Innovation Conference, Nantes, France, 2019 May 20\u201323"},{"key":"717_CR12","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1113\/jphysiol.1929.sp002608","volume":"68","author":"AN Drury","year":"1929","unstructured":"Drury AN, Szent-Gy\u00f6rgyi A (1929) The physiological activity of adenine compounds with special reference to their action upon the mammalian heart. J Physiol 68:213\u2013237. https:\/\/doi.org\/10.1113\/jphysiol.1929.sp002608","journal-title":"J Physiol"},{"key":"717_CR13","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.1021\/tx200237a","volume":"24","author":"EG Duysen","year":"2011","unstructured":"Duysen EG, Koentgen F, Williams GR, Timperley CM, Schopfer LM, Cerasoli DM, Lockridge O (2011) Production of ES1 plasma carboxylesterase knockout mice for toxicity studies. Chem Res Toxicol 24:1891\u20131898. https:\/\/doi.org\/10.1021\/tx200237a","journal-title":"Chem Res Toxicol"},{"key":"717_CR14","doi-asserted-by":"crossref","unstructured":"Effendi WI, Nagano T, Kobayashi K, Nishimura Y (2020) Focusing on adenosine receptors as a potential targeted therapy in human diseases. Cells 9:785. https:\/\/safe.menlosecurity.com\/10.3390\/cells9030785. Accessed Jan 2024","DOI":"10.3390\/cells9030785"},{"key":"717_CR15","doi-asserted-by":"publisher","first-page":"109983","DOI":"10.1016\/j.neuropharm.2024.109983","volume":"253","author":"J Harkins","year":"2024","unstructured":"Harkins J, Langston J, Keith Z-M, Munoz C, Acon-Chen C, Shih T-M (2024) Learning and memory function preserved by delayed A1 adenosine receptor agonist treatment following soman intoxication in rats and a humanized esterase mouse model. Neuropharmacology 253:109983. https:\/\/doi.org\/10.1016\/j.neuropharm.2024.109983. (Published online 05\/03\/2024 and in journal 05\/24\/24)","journal-title":"Neuropharmacology"},{"key":"717_CR16","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1016\/j.bbamem.2010.11.016","volume":"1808","author":"JP Headrick","year":"2011","unstructured":"Headrick JP, Peart JN, Reichelt ME, Haseler LJ (2011) Adenosine and its receptors in the heart: regulation, retaliation and adaptation. Biochim Biophys Acta 1808:1413\u20131428. https:\/\/doi.org\/10.1016\/j.bbamem.2010.11.016","journal-title":"Biochim Biophys Acta"},{"issue":"1","key":"717_CR17","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1007\/s00204-003-0513-4","volume":"78","author":"MA Joosen","year":"2004","unstructured":"Joosen MA, Bueters TH, Helden HM (2004) Cardiovascular effects of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) decisive for its therapeutic efficacy in sarin poisoning. Arch Toxicol 78(1):34\u201339. https:\/\/doi.org\/10.1007\/s00204-003-0513-4","journal-title":"Arch Toxicol"},{"issue":"5","key":"717_CR18","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1001\/jama.1991.03470050093029","volume":"266","author":"JR Keeler","year":"1991","unstructured":"Keeler JR, Hurst CG, Dunn MA (1991) Pyridostigmine used as a nerve agent pretreatment under wartime conditions. JAMA 266(5):693\u2013695","journal-title":"JAMA"},{"key":"717_CR19","doi-asserted-by":"publisher","first-page":"116970","DOI":"10.1016\/j.taap.2024.116970","volume":"488","author":"Z-M Keith","year":"2024","unstructured":"Keith Z-M, Munoz C, Acon-Chen C, Shih T-M (2024) Seizure suppression and neuroprotection in soman-exposed rats following delayed intramuscular treatment of adenosine A1 receptor agonist as an adjunct to standard medical treatment. Toxicol Appl Pharmacol 488:116970. https:\/\/doi.org\/10.1016\/j.taap.2024.116970. (Published online 05\/20\/24)","journal-title":"Toxicol Appl Pharmacol"},{"issue":"3","key":"717_CR20","doi-asserted-by":"publisher","first-page":"1660","DOI":"10.1152\/jn.91062.2008","volume":"101","author":"MJ Lehmkuhle","year":"2009","unstructured":"Lehmkuhle MJ, Thomson K, Scheerlinck P, Pouliot WA, Greger B, Dudek FE (2009) A simple quantitative method for analyzing electrographic status epilepticus in rats. J Neurophysiol 101(3):1660\u20131670. https:\/\/doi.org\/10.1152\/jn.91062.2008","journal-title":"J Neurophysiol"},{"issue":"11","key":"717_CR21","doi-asserted-by":"publisher","first-page":"1673","DOI":"10.1016\/j.bcp.2005.09.002","volume":"70","author":"B Li","year":"2005","unstructured":"Li B, Sedlacek M, Manoharan I, Boopathy R, Duysen EG, Masson P, Lockridge O (2005) Butyrylcholinesterase, paraoxonase, and albumin esterase, but not carboxylesterase, are present in human plasma. Biochem Pharmacol 70(11):1673\u20131684. https:\/\/doi.org\/10.1016\/j.bcp.2005.09.002","journal-title":"Biochem Pharmacol"},{"issue":"9","key":"717_CR22","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1111\/cns.13190","volume":"25","author":"YJ Liu","year":"2019","unstructured":"Liu YJ, Chen J, Li X, Zhou X, Hu YM, Chu SF, Peng Y, Chen NH (2019) Research progress on adenosine in central nervous system diseases. CNS Neurosci Therap 25(9):899\u2013910. https:\/\/doi.org\/10.1111\/cns.13190","journal-title":"CNS Neurosci Therap"},{"key":"717_CR23","doi-asserted-by":"publisher","first-page":"115515","DOI":"10.1016\/j.taap.2021.115515","volume":"419","author":"T Loughery","year":"2021","unstructured":"Loughery T, Whitten K, Acon-Chen C, Shih T-M (2021) Intramuscularly administered A1 adenosine receptor agonists as delayed treatment for organophosphorus nerve agent-induced Status Epilepticus. Toxicol Appl Pharmacol 419:115515. https:\/\/doi.org\/10.1016\/j.taap.2021.115515","journal-title":"Toxicol Appl Pharmacol"},{"key":"717_CR24","doi-asserted-by":"publisher","first-page":"13712","DOI":"10.3390\/molecules171213712","volume":"17","author":"L Luongo","year":"2012","unstructured":"Luongo L, Petrelli R, Gatta L, Giordano C, Guida F, Vita P, Franchetti P, Grifantini M, de Novellis V, Cappellacci L, Maione S (2012) 5\u2019-Chloro-5\u2019-deoxy-(\u00b1) -ENBA, a potent and selective adenosine A1 receptor agonist, alleviates neuropathic pain in mice through functional glial and microglial changes without affecting motor or cardiovascular functions. Molecules 17:13712\u201313726. https:\/\/doi.org\/10.3390\/molecules171213712","journal-title":"Molecules"},{"issue":"1","key":"717_CR25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.eplepsyres.2018.01.010","volume":"141","author":"H McCarren","year":"2018","unstructured":"McCarren H, Arbutus J, Ardinger C, Dunn E, Jackson C, McDonough JH (2018) Dexmedetomidine stops benzodiazepine-refractory nerve agent-induced status epilepticus. Epilepsy Res 141(1):1\u201312. https:\/\/doi.org\/10.1016\/j.eplepsyres.2018.01.010","journal-title":"Epilepsy Res"},{"key":"717_CR26","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/s0149-7634(05)80151-4","volume":"17","author":"JH McDonough","year":"1993","unstructured":"McDonough JH, Shih T-M (1993) Pharmacological modulation of soman-induced seizures. Neurosci Biobehav Rev 17:203\u2013215. https:\/\/doi.org\/10.1016\/s0149-7634(05)80151-4","journal-title":"Neurosci Biobehav Rev"},{"issue":"5","key":"717_CR27","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/s0149-7634(96)00050-4","volume":"21","author":"JH McDonough","year":"1997","unstructured":"McDonough JH, Shih T-M (1997) Neuropharmacological mechanisms of nerve agent-induced seizure and neuropathology. Neurosci Biobehav Rev 21(5):559\u2013579. https:\/\/doi.org\/10.1016\/s0149-7634(96)00050-4","journal-title":"Neurosci Biobehav Rev"},{"issue":"1","key":"717_CR28","first-page":"123","volume":"16","author":"JH McDonough","year":"1995","unstructured":"McDonough JH, Dochterman LW, Smith CD, Shih T-M (1995) Protection against nerve agent-induced neuropathology, but not cardiac pathology, is associated with the anticonvulsant action of the drug treatment. Neurotoxicology 16(1):123\u2013132","journal-title":"Neurotoxicology"},{"key":"717_CR29","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1007\/s002040050637","volume":"73","author":"JH McDonough","year":"1999","unstructured":"McDonough JH, McMonagle J, Copeland T, Zoeffel D, Shih T-M (1999) Comparative evaluation of benzodiazepines for control of soman-induced seizures. Arch Toxicol 73:473\u2013478. https:\/\/doi.org\/10.1007\/s002040050637","journal-title":"Arch Toxicol"},{"key":"717_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/s0920-1211(99)00060-1","volume":"38","author":"JH McDonough","year":"2000","unstructured":"McDonough JH, Zoeffel LD, McMonagle J, Copeland TL, Smith CD, Shih T-M (2000) Anticonvulsant treatment of nerve agent seizures: anticholinergics versus diazepam in soman-intoxicated guinea pigs. Epilepsy Res 38:1\u201314. https:\/\/doi.org\/10.1016\/s0920-1211(99)00060-1","journal-title":"Epilepsy Res"},{"issue":"3","key":"717_CR31","doi-asserted-by":"publisher","first-page":"279","DOI":"10.3109\/01480540903483417","volume":"33","author":"JH McDonough","year":"2010","unstructured":"McDonough JH, McMonagle J, Shih T-M (2010) Time-dependent reduction in the anticonvulsant effectiveness of diazepam against soman-induced seizures in guinea pigs. Drug Chem Toxicol 33(3):279\u2013283. https:\/\/doi.org\/10.3109\/01480540903483417","journal-title":"Drug Chem Toxicol"},{"key":"717_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.taap.2021.115466","volume":"416","author":"K Meads","year":"2021","unstructured":"Meads K, Thomas T, Langston J, Myers T, Shih T-M (2021) Evaluation of adenosine A1 receptor agonists as neuroprotective countermeasures against Soman intoxication in rats. Toxicol Appl Pharmacol 416:1\u201310. https:\/\/doi.org\/10.1016\/j.taap.2021.115466","journal-title":"Toxicol Appl Pharmacol"},{"key":"717_CR33","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1007\/978-1-4899-1051-6_62","volume-title":"Enzymes of cholinesterase family","author":"DH Moore","year":"1995","unstructured":"Moore DH, Clifford CB, Crawford IT, Cole GM, Baggett JM (1995) Review of nerve agent inhibitors and reactivators of acetylcholinesterase. In: Quinn DM, Balasubramanian AS, Doctor BP, Taylor P (eds) Enzymes of cholinesterase family. Plenum Press, New York, pp 297\u2013304"},{"key":"717_CR34","doi-asserted-by":"publisher","first-page":"109966","DOI":"10.1016\/j.neuropharm.2024.109966","volume":"253","author":"C Munoz","year":"2024","unstructured":"Munoz C, Acon-Chen C, Keith Z-M, Shih T-M (2024) Hypothermia as potential therapeutic approach to attenuating soman-induced seizure, neuropathology, and mortality with an adenosine A1 receptor agonist and body cooling. Neuropharmacology 253:109966. https:\/\/doi.org\/10.1016\/j.neuropharm.2024.109966. (Published online 04\/26\/2024 and in journal 05\/24\/24)","journal-title":"Neuropharmacology"},{"key":"717_CR35","unstructured":"Munoz CE, Shih T-M, Acon-Chen C, Keith Z-M (2021) Hypothermia to recover neuropathology and survival after soman-induced seizure. Annual Society for Neuroscience Meeting. Chicago, IL. Abstract #1777"},{"issue":"4","key":"717_CR36","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/j.bbrc.2003.11.006","volume":"312","author":"ZH N\u00e9meth","year":"2003","unstructured":"N\u00e9meth ZH, Leibovich SJ, Deitch EA, Sperl\u00e1gh B, Vir\u00e1g L, Vizi ES, Szab\u00f3 C, Hask\u00f3 G (2003) Adenosine stimulates CREB activation in macrophages via a p38 MAPK-mediated mechanism. Biochem Biophy Res Comm 312(4):883\u2013888. https:\/\/doi.org\/10.1016\/j.bbrc.2003.11.006","journal-title":"Biochem Biophy Res Comm"},{"issue":"12","key":"717_CR37","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1002\/acn3.262","volume":"2","author":"J Niquet","year":"2015","unstructured":"Niquet J, Gezalian M, Baldwin R, Wasterlain CG (2015) Neuroprotective effects of deep hypothermia in refractory status epilepticus. Ann Clin Transl Neurol 2(12):1105\u20131115. https:\/\/doi.org\/10.1002\/acn3.262","journal-title":"Ann Clin Transl Neurol"},{"issue":"1","key":"717_CR38","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1111\/nyas.13147","volume":"1378","author":"J Niquet","year":"2016","unstructured":"Niquet J, Baldwin R, Suchomelova L, Lumley L, Naylor D, Eavey R, Wasterlain CG (2016) Benzodiazepine-refractory status epilepticus: pathophysiology and principles of treatment. Ann N Y Acad Sci 1378(1):166\u2013173. https:\/\/doi.org\/10.1111\/nyas.13147","journal-title":"Ann N Y Acad Sci"},{"key":"717_CR39","doi-asserted-by":"publisher","first-page":"627","DOI":"10.3389\/fphar.2018.00627","volume":"9","author":"M Pastor-Anglada","year":"2018","unstructured":"Pastor-Anglada M, P\u00e9rez-Torras S (2018) Who is who in adenosine transport. Frontiers Pharmacol 9:627. https:\/\/doi.org\/10.3389\/fphar.2018.00627","journal-title":"Frontiers Pharmacol"},{"key":"717_CR40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fnins.2021.708304","volume":"15","author":"B Purnell","year":"2021","unstructured":"Purnell B, Murugan M, Jani R, Boison D (2021) The good, the bad, and the deadly: adenosinergic mechanisms underlying sudden unexpected death in epilepsy. Front Neurosci 15:1\u201315. https:\/\/doi.org\/10.3389\/fnins.2021.708304","journal-title":"Front Neurosci"},{"key":"717_CR41","unstructured":"Reinhardt BC (2020) Of mice and human. JSTO in the News, Vol. 10 (No. 5):7\u20139, published by Defense Threat Reduction Agency, Fort Belvoir, VA, USA"},{"key":"717_CR42","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/0920-1211(90)90095-d","volume":"7","author":"T-M Shih","year":"1990","unstructured":"Shih T-M (1990) Anticonvulsant effects of diazepam and MK-801 in soman poisoning. Epilepsy Res 7:105\u2013116. https:\/\/doi.org\/10.1016\/0920-1211(90)90095-d","journal-title":"Epilepsy Res"},{"key":"717_CR43","doi-asserted-by":"publisher","first-page":"116437","DOI":"10.1016\/j.taap.2023.116437","volume":"464","author":"T-M Shih","year":"2023","unstructured":"Shih T-M (2023) A novel genetically modified mouse seizure model for evaluating anticonvulsive and neuroprotective efficacy of an A1 adenosine receptor agonist following soman intoxication. Toxicol Appl Pharmacol 464:116437. https:\/\/doi.org\/10.1016\/j.taap.2023.116437","journal-title":"Toxicol Appl Pharmacol"},{"key":"717_CR44","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1002\/(sici)1099-1263(199707)17:4<255::aid-jat441>3.0.co;2-d","volume":"17","author":"T-M Shih","year":"1997","unstructured":"Shih T-M, McDonough JH (1997) Neurochemical mechanisms in soman-induced seizures. J Appl Toxicol 17:255\u2013264. https:\/\/doi.org\/10.1002\/(sici)1099-1263(199707)17:4%3c255::aid-jat441%3e3.0.co;2-d","journal-title":"J Appl Toxicol"},{"key":"717_CR45","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/s0149-7634(05)80028-4","volume":"15","author":"T-M Shih","year":"1991","unstructured":"Shih T-M, Koviak TA, Capacio BR (1991) Anticonvulsants for poisoning by the organophosphorus compound soman: pharmacological mechanisms. Neurosci Biobehav Rev 15:349\u2013362. https:\/\/doi.org\/10.1016\/s0149-7634(05)80028-4","journal-title":"Neurosci Biobehav Rev"},{"key":"717_CR46","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/s0041-008x(03)00019-x","volume":"188","author":"T-M Shih","year":"2003","unstructured":"Shih T-M, Duniho SM, McDonough JH (2003) Control of nerve agent-induced seizures if critical for neuroprotection and survival. Toxicol Appl Pharmacol 188:69\u201380. https:\/\/doi.org\/10.1016\/s0041-008x(03)00019-x","journal-title":"Toxicol Appl Pharmacol"},{"key":"717_CR47","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1002\/jcp.21579","volume":"218","author":"C St Hilaire","year":"2009","unstructured":"St Hilaire C, Carroll SH, Chen H, Ravid K (2009) Mechanisms of induction of adenosine receptor genes and its functional significance. J Cell Physiol 218:35\u201344. https:\/\/doi.org\/10.1002\/jcp.21579","journal-title":"J Cell Physiol"},{"key":"717_CR48","first-page":"239","volume-title":"Goodman & Gilman's the pharmacological basis of therapeutics","author":"P Taylor","year":"2011","unstructured":"Taylor P (2011) Chapter 10 anticholinesterase agents. In: Brunton LL, Chabner BA, Knollman BC (eds) Goodman & Gilman\u2019s the pharmacological basis of therapeutics, 12th edn. McGraw-Hill, New York, pp 239\u2013254","edition":"12"},{"issue":"6","key":"717_CR49","doi-asserted-by":"publisher","first-page":"385","DOI":"10.3109\/15376516.2014.920450","volume":"24","author":"TP Thomas","year":"2014","unstructured":"Thomas TP, Shih T-M (2014) Stimulation of central A1 adenosine receptors suppresses seizure and neuropathology in a soman nerve agent seizure rat model. Toxicol Mech Methods 24(6):385\u2013395. https:\/\/doi.org\/10.3109\/15376516.2014.920450","journal-title":"Toxicol Mech Methods"},{"issue":"5","key":"717_CR50","doi-asserted-by":"publisher","first-page":"13147","DOI":"10.26717\/BJSTR.2019.17.003074","volume":"17","author":"TP Thomas","year":"2019","unstructured":"Thomas TP, Shih T-M (2019) The use of adenosine agonists to treat nerve agent-induced seizure and neuropathology. Biomed J Sci Tech Res (BJSTR) 17(5):13147\u201313154. https:\/\/doi.org\/10.26717\/BJSTR.2019.17.003074","journal-title":"Biomed J Sci Tech Res (BJSTR)"},{"issue":"2","key":"717_CR51","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1007\/s12640-019-00034-w","volume":"36","author":"TP Thomas","year":"2019","unstructured":"Thomas TP, Wegener A, Shih T-M (2019) In vivo evaluation of a1 adenosine agonists as novel anticonvulsant medical countermeasures to nerve agent intoxication in a rat soman seizure model. Neurotox Res 36(2):323\u2013333. https:\/\/doi.org\/10.1007\/s12640-019-00034-w","journal-title":"Neurotox Res"},{"issue":"Suppl 1","key":"717_CR52","doi-asserted-by":"publisher","first-page":"171","DOI":"10.3109\/01480549809007409","volume":"21","author":"HP van Helden","year":"1998","unstructured":"van Helden HP, Groen B, Moor E, Westerink BH, Bruijnzeel PL (1998) New generic approach to the treatment of organophosphate poisoning: adenosine receptor mediated inhibition of ACh-release. Drug Chem Toxicol 21(Suppl 1):171\u2013181. https:\/\/doi.org\/10.3109\/01480549809007409","journal-title":"Drug Chem Toxicol"}],"container-title":["Neurotoxicity Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12640-024-00717-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12640-024-00717-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12640-024-00717-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,19]],"date-time":"2024-10-19T17:05:29Z","timestamp":1729357529000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12640-024-00717-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,4]]},"references-count":52,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["717"],"URL":"https:\/\/doi.org\/10.1007\/s12640-024-00717-z","relation":{},"ISSN":["1029-8428","1476-3524"],"issn-type":[{"value":"1029-8428","type":"print"},{"value":"1476-3524","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,4]]},"assertion":[{"value":"14 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 June 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 August 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 September 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The views expressed in this report are those of the author(s) and do not reflect the official policy of the Department of Army, Department of Defense, or the U.S. Government. The experimental protocol was approved by the Institutional Animal Care and Use Committee (IACUC) at the U.S. Army Medical Research Institute of Chemical Defense (USAMRICD), and all procedures were conducted in accordance with the principles stated in the Guide for the Care and Use of Laboratory Animals and the Animal Welfare Act of 1966 (P.L. 89\u2013544), as amended. The facility where this research was conducted is fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International. The use of trade names does not constitute an official endorsement or approval of the use of such commercial hardware or software. This document may not be cited for purposes of advertisement.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclaimers"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"41"}}