Localized intestinal radiation and liquid diet enhance survival and permit evaluation of long-term intestinal responses to high dose radiation in mice
In vivo studies of high dose radiation-induced crypt and intestinal stem cell (ISC) loss and subsequent regeneration are typically restricted to 5-8 days after radiation due to high mortality and immune failure. This study aimed to develop murine radiation models of complete crypt loss that permit l...
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| description | In vivo studies of high dose radiation-induced crypt and intestinal stem cell (ISC) loss and subsequent regeneration are typically restricted to 5-8 days after radiation due to high mortality and immune failure. This study aimed to develop murine radiation models of complete crypt loss that permit longer-term studies of ISC and crypt regeneration, repair and normalization of the intestinal epithelium.
In C57Bl/6J mice, a predetermined small intestinal segment was exteriorized and exposed to 14 Gy-radiation, while a lead shield protected the rest of the body from radiation. Sham controls had segment exteriorization but no radiation. Results were compared to C57Bl/6J mice given 14 Gy-abdominal radiation. Effects of elemental liquid diet feeding from the day prior to radiation until day 7 post-radiation were assessed in both models. Body weight and a custom-developed health score was assessed every day until day 21 post-radiation. Intestine was assessed histologically.
At day 3 after segment radiation, complete loss of crypts occurred in the targeted segment, while adjacent and remaining intestine in segment-radiated mice, and entire intestine of sham controls, showed no detectable epithelial damage. Liquid diet feeding was required for survival of mice after segment radiation. Liquid diet significantly improved survival, body weight recovery and normalization of intestinal epithelium after abdominal radiation. Mice given segment radiation combined with liquid diet feeding showed minimal body weight loss, increased food intake and enhanced health score.
The segment radiation method provides a useful model to study ISC/crypt loss and long-term crypt regeneration and epithelial repair, and may be valuable for future application to ISC transplantation or to genetic mutants that would not otherwise survive radiation doses that lead to complete crypt loss. Liquid diet is a simple intervention that improves survival and facilitates long-term studies of intestine in mice after high dose abdominal or segment radiation. |
| doi_str_mv | 10.1371/journal.pone.0051310 |
| format | Article |
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In C57Bl/6J mice, a predetermined small intestinal segment was exteriorized and exposed to 14 Gy-radiation, while a lead shield protected the rest of the body from radiation. Sham controls had segment exteriorization but no radiation. Results were compared to C57Bl/6J mice given 14 Gy-abdominal radiation. Effects of elemental liquid diet feeding from the day prior to radiation until day 7 post-radiation were assessed in both models. Body weight and a custom-developed health score was assessed every day until day 21 post-radiation. Intestine was assessed histologically.
At day 3 after segment radiation, complete loss of crypts occurred in the targeted segment, while adjacent and remaining intestine in segment-radiated mice, and entire intestine of sham controls, showed no detectable epithelial damage. Liquid diet feeding was required for survival of mice after segment radiation. Liquid diet significantly improved survival, body weight recovery and normalization of intestinal epithelium after abdominal radiation. Mice given segment radiation combined with liquid diet feeding showed minimal body weight loss, increased food intake and enhanced health score.
The segment radiation method provides a useful model to study ISC/crypt loss and long-term crypt regeneration and epithelial repair, and may be valuable for future application to ISC transplantation or to genetic mutants that would not otherwise survive radiation doses that lead to complete crypt loss. Liquid diet is a simple intervention that improves survival and facilitates long-term studies of intestine in mice after high dose abdominal or segment radiation.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0051310</identifier><identifier>PMID: 23236468</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Abdomen ; Analysis of Variance ; Animal models ; Animals ; Apoptosis ; Background radiation ; Biology ; Body weight ; Body weight loss ; Comparative analysis ; Crypts ; Damage detection ; Diet ; Drug dosages ; Epithelium ; Feeding ; Food intake ; Food, Formulated ; Gastroenterology ; Growth factors ; Health aspects ; House mouse ; In vivo methods and tests ; Inflammation ; Intestinal Mucosa - radiation effects ; Intestine ; Intestine, Small - cytology ; Intestine, Small - physiology ; Intestine, Small - radiation effects ; Laboratory animals ; Medicine ; Mice ; Mice, Inbred C57BL ; Models, Animal ; Motility ; Mutants ; Physiology ; Post-radiation ; Radiation ; Radiation (Physics) ; Radiation dosage ; Radiation effects ; Radiation models ; Regeneration ; Regeneration - physiology ; Repair ; Rodents ; Small intestine ; Statistics, Nonparametric ; Stem cells ; Stem Cells - radiation effects ; Studies ; Surgery ; Survival ; Transplantation</subject><ispartof>PloS one, 2012-12, Vol.7 (12), p.e51310</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Van Landeghem et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2012 Van Landeghem et al 2012 Van Landeghem et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-7a569fdeaed84fdf553f8868d2ea60a192913587b02bc06b14bd75553fed2ea83</citedby><cites>FETCH-LOGICAL-c758t-7a569fdeaed84fdf553f8868d2ea60a192913587b02bc06b14bd75553fed2ea83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3517426/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3517426/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23236468$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Van Landeghem, Laurianne</creatorcontrib><creatorcontrib>Blue, Randall Eric</creatorcontrib><creatorcontrib>Dehmer, Jeffrey J</creatorcontrib><creatorcontrib>Henning, Susan J</creatorcontrib><creatorcontrib>Helmrath, Michael A</creatorcontrib><creatorcontrib>Lund, Pauline Kay</creatorcontrib><title>Localized intestinal radiation and liquid diet enhance survival and permit evaluation of long-term intestinal responses to high dose radiation in mice</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>In vivo studies of high dose radiation-induced crypt and intestinal stem cell (ISC) loss and subsequent regeneration are typically restricted to 5-8 days after radiation due to high mortality and immune failure. This study aimed to develop murine radiation models of complete crypt loss that permit longer-term studies of ISC and crypt regeneration, repair and normalization of the intestinal epithelium.
In C57Bl/6J mice, a predetermined small intestinal segment was exteriorized and exposed to 14 Gy-radiation, while a lead shield protected the rest of the body from radiation. Sham controls had segment exteriorization but no radiation. Results were compared to C57Bl/6J mice given 14 Gy-abdominal radiation. Effects of elemental liquid diet feeding from the day prior to radiation until day 7 post-radiation were assessed in both models. Body weight and a custom-developed health score was assessed every day until day 21 post-radiation. Intestine was assessed histologically.
At day 3 after segment radiation, complete loss of crypts occurred in the targeted segment, while adjacent and remaining intestine in segment-radiated mice, and entire intestine of sham controls, showed no detectable epithelial damage. Liquid diet feeding was required for survival of mice after segment radiation. Liquid diet significantly improved survival, body weight recovery and normalization of intestinal epithelium after abdominal radiation. Mice given segment radiation combined with liquid diet feeding showed minimal body weight loss, increased food intake and enhanced health score.
The segment radiation method provides a useful model to study ISC/crypt loss and long-term crypt regeneration and epithelial repair, and may be valuable for future application to ISC transplantation or to genetic mutants that would not otherwise survive radiation doses that lead to complete crypt loss. Liquid diet is a simple intervention that improves survival and facilitates long-term studies of intestine in mice after high dose abdominal or segment radiation.</description><subject>Abdomen</subject><subject>Analysis of Variance</subject><subject>Animal models</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Background radiation</subject><subject>Biology</subject><subject>Body weight</subject><subject>Body weight loss</subject><subject>Comparative analysis</subject><subject>Crypts</subject><subject>Damage detection</subject><subject>Diet</subject><subject>Drug dosages</subject><subject>Epithelium</subject><subject>Feeding</subject><subject>Food intake</subject><subject>Food, Formulated</subject><subject>Gastroenterology</subject><subject>Growth factors</subject><subject>Health aspects</subject><subject>House mouse</subject><subject>In vivo methods and tests</subject><subject>Inflammation</subject><subject>Intestinal Mucosa - radiation 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intestinal radiation and liquid diet enhance survival and permit evaluation of long-term intestinal responses to high dose radiation in mice</title><author>Van Landeghem, Laurianne ; Blue, Randall Eric ; Dehmer, Jeffrey J ; Henning, Susan J ; Helmrath, Michael A ; Lund, Pauline Kay</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-7a569fdeaed84fdf553f8868d2ea60a192913587b02bc06b14bd75553fed2ea83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Abdomen</topic><topic>Analysis of Variance</topic><topic>Animal models</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Background radiation</topic><topic>Biology</topic><topic>Body weight</topic><topic>Body weight loss</topic><topic>Comparative analysis</topic><topic>Crypts</topic><topic>Damage detection</topic><topic>Diet</topic><topic>Drug dosages</topic><topic>Epithelium</topic><topic>Feeding</topic><topic>Food 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evaluation of long-term intestinal responses to high dose radiation in mice</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-12-07</date><risdate>2012</risdate><volume>7</volume><issue>12</issue><spage>e51310</spage><pages>e51310-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>In vivo studies of high dose radiation-induced crypt and intestinal stem cell (ISC) loss and subsequent regeneration are typically restricted to 5-8 days after radiation due to high mortality and immune failure. This study aimed to develop murine radiation models of complete crypt loss that permit longer-term studies of ISC and crypt regeneration, repair and normalization of the intestinal epithelium.
In C57Bl/6J mice, a predetermined small intestinal segment was exteriorized and exposed to 14 Gy-radiation, while a lead shield protected the rest of the body from radiation. Sham controls had segment exteriorization but no radiation. Results were compared to C57Bl/6J mice given 14 Gy-abdominal radiation. Effects of elemental liquid diet feeding from the day prior to radiation until day 7 post-radiation were assessed in both models. Body weight and a custom-developed health score was assessed every day until day 21 post-radiation. Intestine was assessed histologically.
At day 3 after segment radiation, complete loss of crypts occurred in the targeted segment, while adjacent and remaining intestine in segment-radiated mice, and entire intestine of sham controls, showed no detectable epithelial damage. Liquid diet feeding was required for survival of mice after segment radiation. Liquid diet significantly improved survival, body weight recovery and normalization of intestinal epithelium after abdominal radiation. Mice given segment radiation combined with liquid diet feeding showed minimal body weight loss, increased food intake and enhanced health score.
The segment radiation method provides a useful model to study ISC/crypt loss and long-term crypt regeneration and epithelial repair, and may be valuable for future application to ISC transplantation or to genetic mutants that would not otherwise survive radiation doses that lead to complete crypt loss. Liquid diet is a simple intervention that improves survival and facilitates long-term studies of intestine in mice after high dose abdominal or segment radiation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23236468</pmid><doi>10.1371/journal.pone.0051310</doi><tpages>e51310</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-12, Vol.7 (12), p.e51310 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1339065004 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Abdomen Analysis of Variance Animal models Animals Apoptosis Background radiation Biology Body weight Body weight loss Comparative analysis Crypts Damage detection Diet Drug dosages Epithelium Feeding Food intake Food, Formulated Gastroenterology Growth factors Health aspects House mouse In vivo methods and tests Inflammation Intestinal Mucosa - radiation effects Intestine Intestine, Small - cytology Intestine, Small - physiology Intestine, Small - radiation effects Laboratory animals Medicine Mice Mice, Inbred C57BL Models, Animal Motility Mutants Physiology Post-radiation Radiation Radiation (Physics) Radiation dosage Radiation effects Radiation models Regeneration Regeneration - physiology Repair Rodents Small intestine Statistics, Nonparametric Stem cells Stem Cells - radiation effects Studies Surgery Survival Transplantation |
| title | Localized intestinal radiation and liquid diet enhance survival and permit evaluation of long-term intestinal responses to high dose radiation in mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T00%3A32%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Localized%20intestinal%20radiation%20and%20liquid%20diet%20enhance%20survival%20and%20permit%20evaluation%20of%20long-term%20intestinal%20responses%20to%20high%20dose%20radiation%20in%20mice&rft.jtitle=PloS%20one&rft.au=Van%20Landeghem,%20Laurianne&rft.date=2012-12-07&rft.volume=7&rft.issue=12&rft.spage=e51310&rft.pages=e51310-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0051310&rft_dat=%3Cgale_plos_%3EA477084205%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1339065004&rft_id=info:pmid/23236468&rft_galeid=A477084205&rft_doaj_id=oai_doaj_org_article_5e6548c6577e473d8c8f47a9bf4ff86a&rfr_iscdi=true |