Funding Source / Anzahl Molekularbiologie des hämorrhagischen Schocks GM053789

<ol>
	<li>DeCamp, M. M., Demling, R. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Posttraumatic+multisystem+organ+failure.">Posttraumatic multisystem organ failure.</a> JAMA. 260, 530-534 (1988).</li><li>Deitch, E. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multiple+organ+failure.+Pathophysiology+and+potential+future+therapy.">Multiple organ failure. Pathophysiology and potential future therapy.</a> Ann Surg. 216, 117-134 (1992).</li><li>Carrico, C. J., Meakins, J. L., Marshall, J. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multiple+organ+failure+syndrome.">Multiple organ failure syndrome.</a> Arch Surg. 121, 196-208 (1986).</li><li>Hauser, C. J., Joshi, P., Jones, Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Suppression+of+natural+killer+cell+activity+in+patients+with+fracture/soft+tissue+injury.">Suppression of natural killer cell activity in patients with fracture/soft tissue injury.</a> Arch Surg. 132, 1326-1330 (1997).</li><li>Faist, E., Baue, A. E., Dittmer, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multiple+organ+failure+in+polytrauma+patients.">Multiple organ failure in polytrauma patients.</a> J Trauma. 23, 775-787 (1983).</li><li>Baker, C. C., Oppenheimer, L., Stephens, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Epidemiology+of+trauma+deaths.">Epidemiology of trauma deaths.</a> Am J Surg. 140, 144-150 (1980).</li><li>Faist, E., Kupper, T. S., Bakeer, C. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Depression+of+cellular+immunity+after+major+injury+its+association+with+posttraumatic+complications+and+its+reversal+with+immunomodulation.">Depression of cellular immunity after major injury its association with posttraumatic complications and its reversal with immunomodulation.</a> Arch Surg. 121, 1000-1005 (1986).</li><li>Lenz, A., Franklin, G. A., Cheadle, W. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Systemic+inflammation+after+trauma.">Systemic inflammation after trauma.</a> Injury. 38, 1336-1345 (2007).</li><li>Flohe, S., Flohe, S. B., Schade, F. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Immune+response+of+severely+injured+patients--influence+of+surgical+intervention+and+therapeutic+impact.">Immune response of severely injured patients--influence of surgical intervention and therapeutic impact.</a> Lang Arch Surg. 392, 639-648 (2007).</li><li>Ayala, A., Wang, P., Ba, Z. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differential+alterations+in+plasma+IL-6+and+TNF+levels+after+trauma+and+hemorrhage.">Differential alterations in plasma IL-6 and TNF levels after trauma and hemorrhage.</a> Am J Physiol. 260, R167-R171 (1991).</li><li>Kalicke, T., Schlegel, U., Printzen, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Influence+of+a+standardized+closed+soft+tissue+trauma+on+resistance+to+local+infection.+An+experimental+study+in+rats.">Influence of a standardized closed soft tissue trauma on resistance to local infection. An experimental study in rats.</a> J Ortho Res. 21, 373-378 (2003).</li><li>Kobbe, P., Vodovotz, Y., Kaczorowski, D. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+role+of+fracture+associated+soft+tissue+injury+in+the+induction+of+sytemic+inflammation+and+remote+organ+dysfunction+after+bilateral+femur+fracture.">The role of fracture associated soft tissue injury in the induction of sytemic inflammation and remote organ dysfunction after bilateral femur fracture.</a> J Ortho Trauma. 22, 385-390 (2008).</li><li>Kobbe, P., Vodovotz, Y., Kaczorwoski, D. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pattern+of+cytokine+release+and+evolution+of+remote+organ+dysfunction+after+bilateral+femur+fracture.">Pattern of cytokine release and evolution of remote organ dysfunction after bilateral femur fracture.</a> Shock. 30, 43-47 (2008).</li><li>Flohe, S. B., Flohe, S., Schade, F. U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Deterioration+of+the+immune+system+after+trauma:+signals+and+cellular+mechanisms.">Deterioration of the immune system after trauma: signals and cellular mechanisms.</a> Inn. Immun. 14, 333-344 (2008).</li><li>Maier, B., LeFering, R., Lhenert, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Early+versus+late+onset+of+multiple+organ+failure+is+associated+with+differing+patterns+of+plasma+cytokine+biomarker+expression+and+outcome+after+severe+trauma.">Early versus late onset of multiple organ failure is associated with differing patterns of plasma cytokine biomarker expression and outcome after severe trauma.</a> Shock. 28, 668-674 (2007).</li><li>Mestas, J., Hughes, C. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Of+mice+not+men:+differences+between+mouse+and+human+immunology.">Of mice not men: differences between mouse and human immunology.</a> J. Immunol. 172, 2731-2738 (2004).</li><li>Hoth, J. J., Wells, J. D., Brownlee, N. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Toll+like+receptor+4-dependent+responses+to+lung+injury+in+a+murine+model+of+pulmonary+contusion.">Toll like receptor 4-dependent responses to lung injury in a murine model of pulmonary contusion.</a> Shock. 31, 376-381 (2009).</li><li>Matsutani, T., Samy, A. n. a. n. t. h. a., Rue, T. S., W, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transgenic+prolactin-/-+mice:+effect+of+trauma-hemorrhage+on+splenocyte+functions.">Transgenic prolactin-/- mice: effect of trauma-hemorrhage on splenocyte functions.</a> Am J Physiol Cell Physiol. 288, 1109-1116 (2005).</li><li>Matsutani, T., Samy, A. n. a. n. t. h. a., Kang, T. S., S-C, . <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+genetic+background+influences+severity+of+immune+responses+following+trauma-hemorrhage.">Mouse genetic background influences severity of immune responses following trauma-hemorrhage.</a> Cytokine. 30, 168-117 (2005).</li><li>Tsukamoto, T., Pape, H. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+for+trauma+research:+What+are+the+options.">Animal models for trauma research: What are the options.</a> Shock. 31, 3-10 (2008).</li><li>DeMaria, E. J., Pellicane, J. V., Lee, R. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hemorrhagic+shock+in+endotoxin+resistant+mice+:+Improved+survival+unrelated+to+deficient+production+of+tumor+necrosis+factor.">Hemorrhagic shock in endotoxin resistant mice : Improved survival unrelated to deficient production of tumor necrosis factor.</a> J Trauma. 35, 720-724 (1993).</li><li>Jamsa, T., Jalovaara, P., Peng, Z. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+three-point+bending+test+and+peripheral+quantitative+computed+tomography+analysis+in+the+evaluation+of+the+strength+of+mouse+femur.">Comparison of three-point bending test and peripheral quantitative computed tomography analysis in the evaluation of the strength of mouse femur.</a> Bone. 23, 155-161 (1998).</li><li>Bounarens, F., Einhorn, T. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Production+of+a+standard+closed+fracture+in+laboratory+animal+bone.">Production of a standard closed fracture in laboratory animal bone.</a> J Ortho Res. 2, 97-101 (1984).</li><li>Holstein, J. H., Menger, M. D., Culemann, U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+of+a+locking+femur+nail+for+mice.">Development of a locking femur nail for mice.</a> J Biomech. 40, 215-219 (2007).</li><li>Holstein, J. H., Garcia, P., Histing, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Advances+in+the+establishment+of+defined+mouse+models+for+the+study+of+fracture+healing+and+bone+regeneration.">Advances in the establishment of defined mouse models for the study of fracture healing and bone regeneration.</a> J Orthop Trauma. 23, S31-S38 (2009).</li><li>Histing, T., Garcia, P., Matthys, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+internal+locking+plate+to+study+intramembranous+bone+healing+in+a+mouse+femur+fracture+model.">An internal locking plate to study intramembranous bone healing in a mouse femur fracture model.</a> J Orthop Research. 28, 397-402 .</li><li>Manigrasso, M. B., O'Connor, J. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Characterization+of+a+closed+femur+fracture+model+in+mice.">Characterization of a closed femur fracture model in mice.</a> J Ortho Trauma. 18, 687-695 (2004).</li><li>Mark, H., Bergholm, J., Nilsson, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+external+fixation+method+and+device+to+study+fracture+healing+in+rats.">An external fixation method and device to study fracture healing in rats.</a> Acta Orthop Scand. 74, 476-487 (2003).</li><li>Bhandari, M., Shanghnessy, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+minimally+invasive+percutaneous+technique+of+intramedullary+nail+insertion+in+an+animal+model+of+fracture+healing.">A minimally invasive percutaneous technique of intramedullary nail insertion in an animal model of fracture healing.</a> Arch Orthop Trauma Surg. 121, 591-593 (2001).</li><li>Sonanis, S. V., Lampard, A. L., Kamat, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+simple+technique+to+remove+a+bent+femoral+intramedullary+nail+and+broken+interlocking+screw.">A simple technique to remove a bent femoral intramedullary nail and broken interlocking screw.</a> J Trauma. 63, 435-438 (2007).</li><li>Kobbe, P., Kaczorwoski, D. J., Vodovotz, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Local+exposure+of+bone+components+to+injured+soft+tissue+induces+Toll-like+receptor+4-dependent+systemic+inflammation+with+acute+lung+injury.">Local exposure of bone components to injured soft tissue induces Toll-like receptor 4-dependent systemic inflammation with acute lung injury.</a> Shock. 30, 686-691 (2008).</li><li>Bumann, M., Henke, T., Gerngross, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Influence+of+haemorrhagic+shock+on+fracture+healing.">Influence of haemorrhagic shock on fracture healing.</a> Lang Arch Surg. 388, 331-338 (2003).</li><li>Santry, H. P., Alam, H. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fluid+resuscitation:+past,+present,+and+the+future.">Fluid resuscitation: past, present, and the future.</a> Shock. 33, 229-241 (2010).</li><li>Hierholzer, C., Billiar, T. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Molecular+mechanisms+in+the+early+phase+of+hemorrhagic+shock.">Molecular mechanisms in the early phase of hemorrhagic shock.</a> Lang Arch Surg. 386, 302-308 (2001).</li><li>Chaudry, I., Ayala, A., Ertel, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hemorrhage+and+resuscitation:+immunological+aspects.">Hemorrhage and resuscitation: immunological aspects.</a> Am J Physiol. 259, 63-678 (1990).</li><li>Kawasaki, T., Hubbard, W. J., Choudhry, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Trauma-hemorrhage+induces+depressed+splenic+dendritic+cell+functions+in+mice.">Trauma-hemorrhage induces depressed splenic dendritic cell functions in mice.</a> J Immunol. 177, 4514-4520 (2006).</li><li>Kohut, L., Darwiche, S. S., Frank, A. M., Brumfield, J. M., Billiar, T. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fixed+volume+or+Fixed+Pressure:+A+Murine+Model+of+Hemorrhgaic+Shock.">Fixed volume or Fixed Pressure: A Murine Model of Hemorrhgaic Shock.</a> J Vis Exp. , (2010).</li><li>Menzel, C. L., Pfeifer, R., Darwiche, S. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Models+of+lower+extremity+damage+in+mice:+time+course+of+organ+damage+and+immune+response.">Models of lower extremity damage in mice: time course of organ damage and immune response.</a> J Surg Res. 166, e149-e156 (2011).</li><li>Pfeifer, R., Kobbe, P., Darwiche, S. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Role+of+hemorrhage+in+the+induction+of+systemic+inflammation+and+remote+organ+damage:+Analysis+of+combined+pseudo-fracture+and+hemorrhagic+shock.">Role of hemorrhage in the induction of systemic inflammation and remote organ damage: Analysis of combined pseudo-fracture and hemorrhagic shock.</a> J Orthop Res. 29, 270-274 (2011).</li></ol>

Tierversuche wurden in Übereinstimmung mit den Richtlinien und Vorschriften her durch die Institutional Animal Care und Verwenden Ausschusses und der Forschung zu betreiben und Compliance Office der University of Pittsburgh, einer AALAS / AAALAC akkreditierte Institution gesetzt durchgeführt. Tierische Quellen gehören Jackson Laboratories und Charles Rivers Laboratories. Alle Tiere werden umfangreichen Gesundheits-sicherung durch die einzelnen Anbieter sowie die University of Pittsburgh internen Tier die Gesundheit Monitoring-Programme. Diese Forschung ist in Übereinstimmung mit der US-Regierung Prinzipien für die Verwendung von Wirbeltieren durchgeführt. Das Programm ist mit dem USDA registriert und hat einen Letter of Assurance mit der Public Health Service Office of Laboratory Animal Welfare.

Pseudofracture, eine reproduzierbare Mausmodell der sterile Muskel-Skelett-Verletzungen, können zur Beurteilung der posttraumatischen Immunantwort. Die pseudofracture Modell immunologisch ahmt einer Extremität Bruch Umwelt durch Nachbildung der Eigenschaften einer langen Knochenbruch: verletzte Muskel-und Weichgewebe, um beschädigte Knochen und Knochenmark, ohne die nativen Knochen freigelegt 38,39 A biphasischen Immunantwort gesehen werden folgende sein. pseudofracture Trauma, das von einem frühen hyperi...

<table><tbody><tr><td>Surgical blue pad</td><td>Fisher Scientific</td><td>50-7105</td><td></td></tr><tr><td>Sterile Field dressings</td><td>Fisher Scientific</td><td>NC9517505</td><td></td></tr><tr><td>Circulating heating pad 18&quot;x26&quot;</td><td>Harvard Apparatus</td><td>py872-5272</td><td></td></tr><tr><td>Hot bead instrument sterilizer</td><td>VWR international</td><td>11156-002</td><td></td></tr><tr><td>Stainless steel tray 8&quot; x 11&quot;</td><td>VWR international</td><td>62687-049</td><td></td></tr><tr><td>Plexiglass boards (10x15x0.5cm) </td><td>University of Pittsburgh Machine shop</td><td></td><td></td></tr><tr><td>Tape rolls 1&quot;</td><td>Corporate Express</td><td>MMM26001</td><td></td></tr><tr><td>50cc conical tube</td><td>Any Supplier</td><td></td><td></td></tr><tr><td>Straight side wide mouth jars (used as cap for nose cone)</td><td>VWR international</td><td>159000-058</td><td></td></tr><tr><td>Oster A5 clippers w. size 40 blade</td><td>VWR international</td><td>10749-020</td><td></td></tr><tr><td>Surgical scissors (straight &amp;#8211; 12cm)</td><td>Fine Science Tools</td><td>14068-12</td><td></td></tr><tr><td>Hemostats curved -18cm</td><td>Harvard Apparatus</td><td>81331718</td><td></td></tr><tr><td>Forceps (0.8mm-tip, curved-10cm)</td><td>Fine Science Tools</td><td>11050-10</td><td></td></tr><tr><td>Gauze 4&quot;x4&quot;</td><td>Any Supplier</td><td></td><td></td></tr><tr><td>1.5cc microfuge tube</td><td>Any Supplier</td><td></td><td></td></tr><tr><td>Ice bucket</td><td>Any Supplier</td><td></td><td></td></tr><tr><td>Mortar and Pestle </td><td>Fisher Scientific</td><td>12-961AA</td><td></td></tr><tr><td>1cc syringe w/ 25G needle</td><td>Fisher Scientific</td><td>14-826-88</td><td></td></tr><tr><td>20G needle</td><td>Any Supplier</td><td></td><td></td></tr><tr><td>1mL pipetteman</td><td>Any Supplier</td><td></td><td></td></tr><tr><td>1mL pipette tips</td><td>Any Supplier</td><td></td><td></td></tr><tr><td>Falcon polystyrene 8ml tubes </td><td>VWR international</td><td>60819-331</td><td></td></tr><tr><td>Sterilization pouch 3&quot;x8&quot;</td><td>VWR international</td><td>24008</td><td></td></tr><tr><td>Sterilization pouch 5&quot;x10&quot;</td><td>VWR international</td><td>24010</td><td></td></tr><tr><td>MacConkey II Agar plate</td><td>BD Biosciences</td><td>221172</td><td></td></tr><tr><td>Ethyl Alcohol - 200 proof </td><td>Pharmco-AAPER</td><td></td><td>[70%]</td></tr><tr><td>Pentobarbital Sodium (Nembutol Sodium Solution)</td><td>OVATION Pharmaceuticals</td><td></td><td>70mg/kg</td></tr><tr><td>Aerrane (Isoflurane)</td><td>Baxter Internationl Inc.</td><td></td><td>99.9%</td></tr><tr><td>Triadine Povidone Iodine (Betadine)</td><td>Triad disposables</td><td></td><td></td></tr><tr><td>Phosphate Buffered Saline (PBS)</td><td></td><td></td><td></td></tr><tr><td>Buprenorphine HCl</td><td>Bedford Laboratories</td><td></td><td>0.1mg/kg</td></tr></tbody></table>

pseudofracture: an acute peripheral tissue trauma model

Nach Trauma gibt es eine frühe hyper-reaktive entzündliche Reaktion, die zu Multiorganversagen und hoher Sterblichkeit in Trauma-Patienten führen können; diese Reaktion wird häufig durch eine verzögerte Immunsuppression, dass die klinischen Komplikationen der Infektion fügt begleitet und auch die Sterblichkeit erhöhen 1-9. Viele Studien haben begonnen, diese Veränderungen in der Reaktivität des Immunsystems zu bewerten nach einem Trauma. 10-15 Immunologische Studien sind stark durch die Vielzahl von transgenen und Knockout-Mäusen für in vivo Modelle unterstützt;. Diese Stämme Hilfe in detaillierte Untersuchungen zu den molekularen Mechanismen bei der immunologischen Reaktionen beteiligt bewerten 16-21 Die Herausforderung in der experimentellen murinen Trauma Modellierung ist langfristig Untersuchung, wie Frakturfixation Techniken in Mäusen, kann komplex und nicht leicht reproduzierbar. 22-30 Diese pseudofracture Modell, eine leicht reproduziert Trauma-Modell, überwindet diese Schwierigkeiten durch immunologisch imitieren einer Extremität Bruch Umgebung, während gleichzeitig die Bewegungsfreiheit der Tiere und das langfristige Überleben ohne die kontinuierliche, lang anhaltende Anwendung von Betäubungsmitteln. Die Absicht ist es, die Merkmale des Röhrenknochenfrakturen neu; verletzten Muskel-und Weichgewebe, um beschädigte Knochen und Knochenmark, ohne die nativen Knochen freigelegt. Die pseudofracture Modell besteht aus zwei Teilen: einem bilateralen Muskel Quetschverletzung auf die Hinterbeine, durch Injektion eines Knochens Lösung in dieser verletzte Muskeln gefolgt. Der Knochen-Lösung wird von der Ernte der langen Röhrenknochen von beiden Hinterbeine eines alters-und Gewichts-abgestimmt syngenen Spenders vorbereitet. Diese Knochen sind dann zerkleinert und suspendiert in Phosphat-gepufferter Kochsalzlösung bis auf die Knochen-Lösung zu schaffen. Bilaterale Femurfraktur ist eine häufig verwendete und bewährte Modell der Extremitäten Trauma, und war die vergleichende Modell bei der Entwicklung des pseudofracture Modell. Unter der Vielzahl der zur Verfügung stehenden Bruch Modelle, entschieden wir uns zu einer geschlossenen Methode der Fraktur mit Weichteilschaden wie unser Vergleich zu den pseudofracture verwenden, da wir eine sterile noch verhältnismäßig schweren peripheren Gewebe Trauma-Modell wollte. 31 Hämorrhagischen Schock ist ein häufiger Befund bei der Festlegung von schweren Traumata, und die globale Hypoperfusion fügt ein sehr relevantes Element auf ein Trauma-Modell. 32-36 Die pseudofracture Modell leicht mit einem hämorrhagischen Schock-Modell für ein Polytrauma-Modell mit hohem Schweregrad kombiniert werden . 37

Watch this Scientific Journal Video about Pseudofracture: An Acute Peripheral Tissue Trauma Model at JoVE.com

Pseudofracture: An Acute Peripheral Tissue Trauma Model

Pseudofracture, eine reproduzierbare Mausmodell der sterile Muskel-Skelett-Verletzungen, können zur Beurteilung der späten Begriff posttraumatische Immunantwort. Dieser Artikel beschreibt die verfahrensrechtlichen Ausführung des Modells Schritt für Schritt, einschließlich des Potenzials für experimentelles Modell Kombinationen Studie Polytrauma ermöglichen.

Pseudofracture: eine akute periphere Gewebe Trauma-Modell

Following trauma there is an early hyper-reactive inflammatory response that can lead to multiple organ dysfunction and high mortality in trauma patients; ...

pseudofracture-an-acute-peripheral-tissue-trauma-model

Universidad de Cartagena UDEC

Research

JoVE Journal

Medicine

14.7K Aufrufe.  University of Pittsburgh. Pseudofracture, eine reproduzierbare Mausmodell der sterile Muskel-Skelett-Verletzungen, können zur Beurteilung der späten Begriff posttraumatische Immunantwort. Dieser Artikel beschreibt die verfahrensrechtlichen Ausführung des Modells Schritt für Schritt, einschließlich des Potenzials für experimentelles Modell Kombinationen Studie Polytrauma ermöglichen.

Serie: Pseudofracture: An Acute Peripheral Tissue Trauma Model

Creating Rigidly Stabilized Fractures for Assessing Intramembranous Ossification, Distraction Osteogenesis, or Healing of Critical Sized Defects

Assessing modes of skeletal repair is essential for developing therapies to be used clinically to treat fractures. Mechanical stability plays a large role in healing of bone injuries. In the worst-case scenario mechanical instability can lead to delayed or non-union in humans. However, motion can also stimulate the healing process. In fractures that have motion cartilage forms to stabilize the fracture bone ends, and this cartilage is gradually replaced by bone through recapitulation of the developmental process of endochondral ossification. In contrast, if a bone fracture is rigidly stabilized bone forms directly via intramembranous ossification. Clinically, both endochondral and intramembranous ossification occur simultaneously. To effectively replicate this process investigators insert a pin into the medullary canal of the fractured bone as described by Bonnarens4. This experimental method provides excellent lateral stability while allowing rotational instability to persist. However, our understanding of the mechanisms that regulate these two distinct processes can also be enhanced by experimentally isolating each of these processes. We have developed a stabilization protocol that provides rotational and lateral stabilization. In this model, intramembranous ossification is the only mode of healing that is observed, and healing parameters can be compared among different strains of genetically modified mice 5-7, after application of bioactive molecules 8,9, after altering physiological parameters of healing 10, after modifying the amount or time of stabilization 11, after distraction osteogenesis 12, after creation of a non-union 13, or after creation of a critical sized defect. Here, we illustrate how to apply the modified Ilizarov fixators for studying tibial fracture healing and distraction osteogenesis in mice.

This article describes a method for stabilizing long bone fractures that is based on the application of modified Ilizarov external fixators 1-3. After application of the fixators and creation of the bone injury, healing can be assessed, distraction osteogenesis can be performed, or non-union or critical sized defect can be created and used to study therapeutic interventions.

Erstellen Starr stabilisierte Frakturen zur Beurteilung intramembranöse Ossifikation, Distraktionsosteogenese, oder Heilung von kritischer Größe Mängel

Assessing modes of skeletal repair is essential for developing therapies to be used clinically to treat fractures. Mechanical stability plays a large role ...

Forschung

Medizin

A Simple Critical-sized Femoral Defect Model in Mice

While bone has a remarkable capacity for regeneration, serious bone trauma often results in damage that does not properly heal. In fact, one tenth of all limb bone fractures fail to heal completely due to the extent of the trauma, disease, or age of the patient. Our ability to improve bone regenerative strategies is critically dependent on the ability to mimic serious bone trauma in test animals, but the generation and stabilization of large bone lesions is technically challenging. In most cases, serious long bone trauma is mimicked experimentally by establishing a defect that will not naturally heal. This is achieved by complete removal of a bone segment that is larger than 1.5 times the diameter of the bone cross-section. The bone is then stabilized with a metal implant to maintain proper orientation of the fracture edges and allow for mobility. 
Due to their small size and the fragility of their long bones, establishment of such lesions in mice are beyond the capabilities of most research groups. As such, long bone defect models are confined to rats and larger animals. Nevertheless, mice afford significant research advantages in that they can be genetically modified and bred as immune-compromised strains that do not reject human cells and tissue.
Herein, we demonstrate a technique that facilitates the generation of a segmental defect in mouse femora using standard laboratory and veterinary equipment. With practice, fabrication of the fixation device and surgical implantation is feasible for the majority of trained veterinarians and animal research personnel. Using example data, we also provide methodologies for the quantitative analysis of bone healing for the model.

Animal models are frequently employed to mimic serious bone injury in biomedical research. Due to their small size, establishment of stabilized bone lesions in mice are beyond the capabilities of most research groups. Herein, we describe a simple method for establishing and analyzing experimental femoral defects in mice.

Eine einfache Kritische große Femoral Defect Modell an der Maus

While bone has a remarkable capacity for regeneration, serious bone trauma often results in damage that does not properly heal. In fact, one tenth of all ...

A Mouse Model of Orthopedic Surgery to Study Postoperative Cognitive Dysfunction and Tissue Regeneration

Surgery is commonly used to improve and maintain quality of life. Unfortunately, in vulnerable patients such as the elderly, complications may occur and significantly diminish the outcome. Indeed, after routine orthopedic surgery to repair a fracture, as many as 50% of elderly patients suffer from neurologic complications like delirium. Also, the capacity to heal and regenerate tissue after surgery decreases with age, and can impact the quality of fracture repair and even osseous integration of implants. Thus, a better understanding of mechanisms that drive these age-dependent changes could provide strategic targets to minimize risk for such complications and optimize outcomes. Here, we introduce a clinically relevant mouse model of tibial fracture. The postoperative changes in these mice mimic some of the cognitive impairments commonly observed after routine orthopedic surgery in humans. Briefly, an incision is performed in the right hind limb under strictly aseptic conditions. Muscles are disassociated, and a 0.38-mm stainless steel pin is inserted into the upper crest of the tibia, inside the intramedullary canal. Osteotomy is then performed, and the wound is stapled. We have used this model to investigate the effects of surgical trauma on postoperative neuroinflammation and behavioral changes. By applying this fracture model in combination with parabiosis, a surgical model in which 2 mice are anastomosed, we have studied cells and secreted factors that systemically rejuvenate organ function and tissue regeneration after injury. By following our step-by-step protocol, these models can be reproduced with high fidelity, and can be adapted to interrogate many biologic pathways that are altered by surgical trauma.

This protocol describes a mouse model of orthopedic surgery that has been used to study mechanisms of postoperative neuroinflammation and behavioral changes, and when combined with parabiosis, to study tissue regeneration during aging.

Ein Maus-Modell der orthopädischen Chirurgie, Postoperative kognitive Dysfunktion und Geweberegeneration zu studieren

Surgery is commonly used to improve and maintain quality of life. Unfortunately, in vulnerable patients such as the elderly, complications may occur and ...

A Minimally Invasive Model to Analyze Endochondral Fracture Healing in Mice Under Standardized Biomechanical Conditions

Bone healing models are necessary to analyze the complex mechanisms of fracture healing to improve clinical fracture treatment. During the last decade, an increased use of mouse models in orthopedic research was noted, most probably because mouse models offer a large number of genetically-modified strains and special antibodies for the analysis of molecular mechanisms of fracture healing. To control the biomechanical conditions, well-characterized osteosynthesis techniques are mandatory, also in mice. Here, we report on the design and use of a closed bone healing model to stabilize femur fractures in mice. The intramedullary screw, made of medical-grade stainless steel, provides through fracture compression an axial and rotational stability compared to the mostly used simple intramedullary pins, which show a complete lack of axial and rotational stability. The stability achieved by the intramedullary screw allows the analysis of endochondral healing. A large amount of callus tissue, received after stabilization with the screw, offers ideal conditions to harvest tissue for biochemical and molecular analyses. A further advantage of the use of the screw is the fact that the screw can be inserted into the femur with a minimally invasive technique without inducing damage to the soft tissue. In conclusion, the screw is a unique implant that can ideally be used in closed fracture healing models offering standardized biomechanical conditions.

This protocol describes a minimally invasive osteosynthesis technique using an intramedullary screw for standardized stabilization of femur fractures, which can be used to analyze endochondral bone healing in mice.

Eine Minimal-Invasive Modell Endochondral Frakturheilung bei Mäusen unter standardisierten Bedingungen biomechanische Analyse

Bone healing models are necessary to analyze the complex mechanisms of fracture healing to improve clinical fracture treatment. During the last decade, an ...

The Generation of Closed Femoral Fractures in Mice: A Model to Study Bone Healing

Bone fractures impose a tremendous socio-economic burden on patients, in addition to significantly affecting their quality of life. Therapeutic strategies that promote efficient bone healing are non-existent and in high demand. Effective and reproducible animal models of fractures healing are needed to understand the complex biological processes associated with bone regeneration. Many animal models of fracture healing have been generated over the years; however, murine fracture models have recently emerged as powerful tools to study bone healing. A variety of open and closed models have been developed, but the closed femoral fracture model stands out as a simple method for generating rapid and reproducible results in a physiologically relevant manner. The goal of this surgical protocol is to generate unilateral closed femoral fractures in mice and facilitate a post-fracture stabilization of the femur by inserting an intramedullary steel rod. Although devices such as a nail or a screw offer greater axial and rotational stability, the use of an intramedullary rod provides a sufficient stabilization for consistent healing outcomes without producing new defects in the bone tissue or damaging nearby soft tissue. Radiographic imaging is used to monitor the progression of callus formation, bony union, and subsequent remodeling of the bony callus. Bone healing outcomes are typically associated with the strength of the healed bone and measured with torsional testing. Still, understanding the early cellular and molecular events associated with fracture repair is critical in the study of bone tissue regeneration. The closed femoral fracture model in mice with intramedullary fixation serves as an attractive platform to study bone fracture healing and evaluate therapeutic strategies to accelerate healing.

The murine closed femoral fracture model is a powerful platform to study fracture healing and novel therapeutic strategies to accelerate bone regeneration. The goal of this surgical protocol is to generate unilateral closed femoral fractures in mice using an intramedullary steel rod to stabilize the femur.

Die Generation der geschlossenen femoralen Frakturen bei Mäusen: ein Modell zur Knochenheilung

Bone fractures impose a tremendous socio-economic burden on patients, in addition to significantly affecting their quality of life. Therapeutic strategies ...

Fracture Apparatus Design and Protocol Optimization for Closed-stabilized Fractures in Rodents

The reliable generation of consistent stabilized fractures in animal models is essential for understanding the biology of bone regeneration and developing therapeutics and devices. However, available injury models are plagued by inconsistency resulting in wasted animals and resources and imperfect data. To address this problem of fracture heterogeneity, the purpose of the method described herein is to optimize fracture generation parameters specific to each animal and yield a consistent fracture location and pattern. This protocol accounts for variations in bone size and morphology that may exist between mouse strains and can be adapted to generate consistent fractures in other species, such as rat. Additionally, a cost-effective, adjustable fracture apparatus is described. Compared to current stabilized fracture techniques, the optimization protocol and new fracture apparatus demonstrate increased consistency in stabilized fracture patterns and locations. Using optimized parameters specific to the sample type, the described protocol increases the precision of induced traumas, minimizing the fracture heterogeneity typically observed in closed-fracture generation procedures.

The goal of the protocol is to optimize the fracture generation parameters to yield consistent fractures. This protocol accounts for the variations in bone size and morphology that may exist between animals. Additionally, a cost-effective, adjustable fracture apparatus is described.

Fraktur Apparat Design und Protokoll-Optimierung für geschlossen-stabilisierten Frakturen bei Nagern

The reliable generation of consistent stabilized fractures in animal models is essential for understanding the biology of bone regeneration and developing ...

Traumatic Peripheral Nerve Injury in Mice

Traumatic peripheral nerve injury (TPNI) is a common cause of morbidity following orthopedic trauma. Reproducible and precise methods of injuring nerve and denervating muscle have long been a goal in musculoskeletal research. Many traumatically injured limbs have nerve trauma that defines the long-term patient outcome. Over several years, precise methods of producing microsurgical nerve injuries have been developed, including crush, lacerations, and nerve-gap grafting, allowing for reproducible outcome assessments. Moreover, newer methods are created for calibrated crush injuries that offer clinically relevant correlations with outcomes used to assess human patients. The principles of minimal manipulation to ensure low variability in nerve injury allow for adding still more associated tissue injuries into these models. This includes direct muscle crush and other components of limb injury. Finally, atrophy assessment and precise analysis of behavioral outcomes make these methods a complete package for studying musculoskeletal trauma that realistically incorporates all the elements of human traumatic limb injury.

The present protocol describes traumatic peripheral nerve injuries (TPNIs), including precisely calibrated crush, strictly aligned and misaligned laceration, as well as grafted and non-grafted gaps of the sciatic nerve in mice. Custom-designed sensors are developed to gauge nerve trauma, induced with commonly available tools to ensure reproducible post-TPNI outcomes.

Traumatic peripheral nerve injury (TPNI) is a common cause of morbidity following orthopedic trauma. Reproducible and precise methods of injuring nerve ...

Neurowissenschaften

The Tibial Fracture-Pin Model: A Clinically Relevant Mouse Model of Orthopedic Injury

The tibial fracture-pin model is a mouse model of orthopedic trauma and surgery that recapitulates the complex muscle, bone, nerve, and connective tissue damage that manifests with this type of injury in humans. This model was developed because previous models of orthopedic trauma did not include simultaneous injury to multiple tissue types (bone, muscle, nerves) and were not truly representative of human complex orthopedic trauma. The authors therefore modified previous models of orthopedic trauma and developed the tibial fracture-pin model. This modified fracture model consists of a unilateral open tibial fracture with intramedullary nail (IMN) internal fixation and simultaneous tibialis anterior (TA) muscle injury, resulting in mechanical allodynia that lasts up to 5 weeks post injury. This series of protocols outlines the detailed steps to perform the clinically relevant orthopedic trauma tibial fracture-pin model, followed by a modified hot plate assay to examine nociceptive changes after orthopedic injury. Taken together, these detailed, reproducible protocols will allow pain researchers to expand their toolkit for studying orthopedic trauma-induced pain.

The tibial fracture-pin model is a clinically relevant model of orthopedic trauma comprising a unilateral open tibial fracture with intramedullary nail internal fixation and simultaneous injury to the tibialis anterior muscle. Thermal sensitivity in this model can be measured using a 45 s hot plate paradigm.

The tibial fracture-pin model is a mouse model of orthopedic trauma and surgery that recapitulates the complex muscle, bone, nerve, and connective tissue ...

Transverse Fracture of the Mouse Femur with Stabilizing Pin

Fracture repair is an essential function of the skeleton that cannot be reliably modeled in vitro. A mouse injury model is an efficient approach to test whether a gene, gene product or drug influences bone repair because murine bones recapitulate the stages observed during human fracture healing. When a mouse or human breaks a bone, an inflammatory response is initiated, and the periosteum, a stem cell niche surrounding the bone itself, is activated and expands. Cells residing in the periosteum then differentiate to form a vascularized soft callus. The transition from the soft callus to a hard callus occurs as the recruited skeletal progenitor cells differentiate into mineralizing cells, and the bridging of the fractured ends results in the bone union. The mineralized callus then undergoes remodeling to restore the original shape and structure of the healed bone. Fracture healing has been studied in mice using various injury models. Still, the best way to recapitulate this entire biological process is to break through the cross-section of a long bone that encompasses both cortices. This protocol describes how a stabilized, transverse femur fracture can be safely performed to assess healing in adult mice. A surgical protocol including detailed harvesting and imaging techniques to characterize the different stages of fracture healing is also provided.

This protocol describes a method to perform fractures on adult mice and monitor the healing process.

Querbruch des Mausfemurs mit stabilisierendem Stift

Fracture repair is an essential function of the skeleton that cannot be reliably modeled in vitro. A mouse injury model is an efficient approach to test ...

Biologie

Establishing a Diaphyseal Femur Fracture Model in Mice

Bones have a significant regenerative capacity. However, fracture healing is a complex process, and depending on the severity of the lesions and the age and overall health status of the patient, failures can occur, leading to delayed union or nonunion. Due to the increasing number of fractures resulting from high-energy trauma and aging, the development of innovative therapeutic strategies to improve bone repair based on the combination of skeletal/mesenchymal stem/stromal cells and biomimetic biomaterials is urgently needed. To this end, the use of reliable animal models is fundamental to better understanding the key cellular and molecular mechanisms that determine the healing outcomes. Of all the models, the mouse is the preferred research model because it offers a wide variety of transgenic strains and reagents for experimental analysis. However, the establishment of fractures in mice may be technically challenging due to their small size. Therefore, this article aims to demonstrate the procedures for the surgical establishment of a diaphyseal femur fracture in mice, which is stabilized with an intramedullary wire and resembles the most common bone repair process, through cartilaginous callus formation.

This protocol describes a surgical procedure for the establishment of a diaphyseal fracture in the femur of mice, which is stabilized with an intramedullary wire, for fracture healing studies.

Etablierung eines diaphysären Femurfrakturmodells bei Mäusen

Bones have a significant regenerative capacity. However, fracture healing is a complex process, and depending on the severity of the lesions and the age ...