{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:33:57Z","timestamp":1791074037281,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,6,8]],"date-time":"2011-06-08T00:00:00Z","timestamp":1307491200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2011,7]]},"abstract":"<jats:p><jats:bold>BACKGROUND AND PURPOSE<\/jats:bold> Electrical stimulation of the vagus nerve reduces intestinal inflammation following mechanical handling, thereby shortening post\u2010operative ileus in mice. Previous studies in a sepsis model showed that this cholinergic anti\u2010inflammatory pathway can be activated pharmacologically by central administration of semapimod, an inhibitor of p38 mitogen\u2010activated protein kinase. We therefore evaluated the effect of intracerebroventricular (i.c.v.) semapimod on intestinal inflammation and post\u2010operative ileus in mice.<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold> Mice underwent a laparotomy or intestinal manipulation 1\u2003h after i.c.v. pre\u2010treatment with semapimod (1\u2003\u00b5g\u00b7kg<jats:sup>\u22121<\/jats:sup>) or saline. Drugs were administered through a cannula placed in the left lateral ventricle 1 week prior to experimentation. Twenty\u2010four hours after surgery, gastric emptying was measured using scintigraphy, and the degree of intestinal inflammation was assessed. Finally, activation of brain regions was assessed using quantitative immunohistochemistry for c\u2010fos.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold> Intestinal manipulation induced inflammation of the manipulated intestine and significantly delayed gastric emptying, 24\u2003h after surgery in saline\u2010treated animals. Semapimod significantly reduced this inflammation and improved gastric emptying. Vagotomy enhanced the inflammatory response induced by intestinal manipulation and abolished the anti\u2010inflammatory effect of semapimod. Semapimod but not saline induced a significant increase in c\u2010fos expression in the paraventricular nucleus, the nucleus of the solitary tract and the dorsal motor nucleus of the vagus nerve.<\/jats:p><jats:p><jats:bold>CONCLUSIONS AND IMPLICATIONS<\/jats:bold> Our findings show that i.c.v. semapimod reduces manipulation\u2010induced intestinal inflammation and prevented post\u2010operative ileus. This anti\u2010inflammatory effect depends on central activation of the vagus nerve.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2011.01296.x","type":"journal-article","created":{"date-parts":[[2011,3,4]],"date-time":"2011-03-04T07:47:50Z","timestamp":1299224870000},"page":"1007-1016","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Central activation of the cholinergic anti\u2010inflammatory pathway reduces surgical inflammation in experimental post\u2010operative ileus"],"prefix":"10.1111","volume":"163","author":[{"given":"FO","family":"The","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Cailotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"van der Vliet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"WJ","family":"de Jonge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"RJ","family":"Bennink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"RM","family":"Buijs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GE","family":"Boeckxstaens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,6,8]]},"reference":[{"issue":"1","key":"e_1_2_8_2_1","first-page":"S1","article-title":"Guide to Receptors and Channels (GRAC), 4th Edition","volume":"158","author":"Alexander SPH","year":"2009","journal-title":"Br J Pharmacol"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903040209"},{"key":"e_1_2_8_4_1","first-page":"1099","article-title":"Validation of gastric\u2010emptying scintigraphy of solids and liquids in mice using dedicated animal pinhole scintigraphy","volume":"44","author":"Bennink RJ","year":"2003","journal-title":"J Nucl Med"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1067\/mva.2002.129643"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20011714"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03401550"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903490205"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1566-0702(00)00233-2"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/35013070"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(10)62858-2"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03401812"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19960101)364:1<78::AID-CNE7>3.0.CO;2-P"},{"key":"e_1_2_8_14_1","volume-title":"The Mouse Brain in Stereotaxic Coordinates","author":"Franklin KBJ","year":"2007"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.08.016"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.03.029"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(85)90054-1"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(03)01197-1"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.04.017"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1229"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-199811000-00004"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1999.0029900378"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(00)70214-9"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.SLA.0000055742.79045.7E"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.4.2293"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/00024382-199711000-00005"},{"key":"e_1_2_8_27_1","first-page":"719","article-title":"Macrophages in the external muscle layers of mammalian intestines","volume":"10","author":"Mikkelsen HB","year":"1995","journal-title":"Histol Histopathol"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0600506103"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0361-9230(80)80006-2"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706303"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.07.022"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30555"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.68.040504.094635"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01339"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-7254.2006.00255.x"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2004.11.003"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2005.089615"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.10.017"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.02.022"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.04.057"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1999.277.1.G79"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1476-5381.2011.01296.x","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1476-5381.2011.01296.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1476-5381.2011.01296.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,15]],"date-time":"2023-10-15T23:32:36Z","timestamp":1697412756000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/j.1476-5381.2011.01296.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,6,8]]},"references-count":40,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2011,7]]}},"alternative-id":["10.1111\/j.1476-5381.2011.01296.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1476-5381.2011.01296.x","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,6,8]]},"assertion":[{"value":"2011-06-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}