وأيد هذا العمل من قبل CDMRP، USUHS G188LE المنح، G188MG، وG188QC (HL ل)، ومركز USUHS لدراسة باضطراب ما بعد الصدمة.

<ol>
	<li>Adrien, J., Dugovic, C., Martin, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sleep-wakefulness+patterns+in+the+helpless+rat.">Sleep-wakefulness patterns in the helpless rat.</a> Physiol. Behav. 49, 257-262 (1991).</li><li>Bai, X., Wu, J., Zhang, Q., Alesci, S., Manoli, I., Blackman, M. R., Chrousos, G. P., Goldstein, A. L., Rennert, O. M., Su, Y. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Third-generation+human+mitochondria-focused+cDNA+microarray+and+its+bioinformatic+tools+for+analysis+of+gene+expression.">Third-generation human mitochondria-focused cDNA microarray and its bioinformatic tools for analysis of gene expression.</a> Biotechniques. 42, 365-375 (2007).</li><li>Blaszczyk, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Startle+response+to+short+acoustic+stimuli+in+rats.">Startle response to short acoustic stimuli in rats.</a> Acta Neurobiol. Exp. (Wars.). 63, 25-30 (2003).</li><li>Braga, M. F., roniadou-Anderjaska, V., Manion, S. T., Hough, C. J., Li, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stress+impairs+alpha(1A)+adrenoceptor-mediated+noradrenergic+facilitation+of+GABAergic+transmission+in+the+basolateral+amygdala.">Stress impairs alpha(1A) adrenoceptor-mediated noradrenergic facilitation of GABAergic transmission in the basolateral amygdala.</a> Neuropsychopharmacology. 29, 45-58 (2004).</li><li>Bremner, J. D., Vythilingam, M., Vermetten, E., Anderson, G., Newcomer, J. W., Charney, D. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+glucocorticoids+on+declarative+memory+function+in+major+depression.">Effects of glucocorticoids on declarative memory function in major depression.</a> Biol. Psychiatry. 55, 811-815 (2004).</li><li>Garrick, T., Morrow, N., Eth, S., Marciano, D., Shalev, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Psychophysiologic+parameters+of+traumatic+stress+disorder+in+rats.">Psychophysiologic parameters of traumatic stress disorder in rats.</a> Ann. N.Y. Acad. Sci. 821, 533-537 (1997).</li><li>Garrick, T., Morrow, N., Shalev, A. Y., Eth, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stress-induced+enhancement+of+auditory+startle:+an+animal+model+of+posttraumatic+stress+disorder.">Stress-induced enhancement of auditory startle: an animal model of posttraumatic stress disorder.</a> Psychiatry. 64, 346-354 (2001).</li><li>Hsiao, Y. H., Su, Y. A., Tsai, H. D., Mason, J. T., Chou, M. C., Man, Y. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Increased+invasiveness+and+aggressiveness+in+breast+epithelia+with+cytoplasmic+p63+expression.">Increased invasiveness and aggressiveness in breast epithelia with cytoplasmic p63 expression.</a> Int. J. Biol. Sci. 6, 428-442 (2010).</li><li>Jiang, X., Xing, G., Yang, C., Verma, A., Zhang, L., Li, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stress+Impairs+5-HT(2A)+Receptor-Mediated+Serotonergic+Facilitation+of+GABA+Release+in+Juvenile+Rat+Basolateral+Amygdala.">Stress Impairs 5-HT(2A) Receptor-Mediated Serotonergic Facilitation of GABA Release in Juvenile Rat Basolateral Amygdala.</a> Neuropsychopharmacology. , (2008).</li><li>Jiang, X., Zhang, Z. J., Zhang, S., Gamble, E. H., Jia, M., Ursano, R. J., Li, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=5-HT2A+receptor+antagonism+by+MDL+11,939+during+inescapable+stress+prevents+subsequent+exaggeration+of+acoustic+startle+response+and+reduced+body+weight+in+rats.">5-HT2A receptor antagonism by MDL 11,939 during inescapable stress prevents subsequent exaggeration of acoustic startle response and reduced body weight in rats.</a> J. Psychopharmacol. , (2009).</li><li>Maher, H. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sleep+deprivation:+are+you+a+victim.">Sleep deprivation: are you a victim.</a> AAOHN. J. 54, 548 (2006).</li><li>Maier, S. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Exposure+to+the+stressor+environment+prevents+the+temporal+dissipation+of+behavioral+depression/learned+helplessness.">Exposure to the stressor environment prevents the temporal dissipation of behavioral depression/learned helplessness.</a> Biol. Psychiatry. 49, 763-773 (2001).</li><li>North, C. S., Suris, A. M., Davis, M., Smith, R. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Toward+validation+of+the+diagnosis+of+posttraumatic+stress+disorder.">Toward validation of the diagnosis of posttraumatic stress disorder.</a> Am. J. Psychiatry. 166, 34-41 (2009).</li><li>Orr, S. P., Metzger, L. J., Pitman, R. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Psychophysiology+of+post-traumatic+stress+disorder.">Psychophysiology of post-traumatic stress disorder.</a> Psychiatr. Clin. North Am. 25, 271-293 (2002).</li><li>Orr, S. P., Roth, W. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Psychophysiological+assessment:+clinical+applications+for+PTSD.">Psychophysiological assessment: clinical applications for PTSD.</a> J. Affect. Disord. 61, 225-240 (2000).</li><li>Pitman, R. K., Orr, S. P., Shalev, A. Y., Metzger, L. J., Mellman, 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=Psychophysiological+alterations+in+post-traumatic+stress+disorder.">Psychophysiological alterations in post-traumatic stress disorder.</a> Semin. Clin. Neuropsychiatry. 4, 234-241 (1999).</li><li>Servatius, R. J., Ottenweller, J. E., Natelson, B. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Delayed+startle+sensitization+distinguishes+rats+exposed+to+one+or+three+stress+sessions:+Further+evidence+toward+an+animal+model+of+PTSD.">Delayed startle sensitization distinguishes rats exposed to one or three stress sessions: Further evidence toward an animal model of PTSD.</a> Biological Psychiatry. 38, 539-546 (1995).</li><li>Su, Y. A., Zhang, Q., Su, D. M., Tang, M. X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rat+Mitochondrion-Neuron+Focused+Microarray+(rMNChip)+and+Bioinformatics+Tools+for+Rapid+Identification+of+Differential+Pathways+in+Brain+Tissues.">Rat Mitochondrion-Neuron Focused Microarray (rMNChip) and Bioinformatics Tools for Rapid Identification of Differential Pathways in Brain Tissues.</a> Int. J. Biol. Sci. 7, 308-322 (2011).</li><li>Su, D. M., Zhang, Q., Wang, X., He, P., Zhu, Y. J., Zhao, J., Rennert, O. M., Su, Y. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Two+types+of+human+malignant+melanoma+cell+lines+revealed+by+expression+patterns+of+mitochondrial+and+survival-apoptosis+genes:+implications+for+malignant+melanoma+therapy.+Mol.">Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy. Mol.</a> Cancer Ther. , (2009).</li><li>Su, Y. A., Li, H., He, P., Webster, M. J., Zhang, Q., Zhang, L., Wang, X., Su, D. M., Ursano, R. J., Rennert, O. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Identification+of+stress-responsive+genes,+canonical+pathways,+molecular+networks+and+drug+targets+in+brain+tissues+of+human+and+animals+for+systems-biology+study+of+post-traumatic+stress+disorder.">Identification of stress-responsive genes, canonical pathways, molecular networks and drug targets in brain tissues of human and animals for systems-biology study of post-traumatic stress disorder.</a> , (2009).</li><li>Su, Y. A., Wu, J., Zhang, L., Zhang, Q., Su, D. M., He, P., Wang, B. D., Li, H., Webster, M. J., Rennert, O. M., Ursano, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dysregulated+mitochondrial+genes+and+networks+with+drug+targets+in+postmortem+brain+of+patients+with+posttraumatic+stress+disorder+(PTSD)+revealed+by+human+mitochondria-focused+cDNA+microarrays.">Dysregulated mitochondrial genes and networks with drug targets in postmortem brain of patients with posttraumatic stress disorder (PTSD) revealed by human mitochondria-focused cDNA microarrays.</a> Int. J Biol. Sci. 4, 223-235 (2008).</li><li>Su, Y. A., Yang, J., Tao, L., Nguyen, H., He, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Undetectable+and+Decreased+Expression+of+KIAA1949+(Phostensin)+Encoded+on+Chromosome+6p21.33+in+Human+Breast+Cancers+Revealed+by+Transcriptome+Analysis.">Undetectable and Decreased Expression of KIAA1949 (Phostensin) Encoded on Chromosome 6p21.33 in Human Breast Cancers Revealed by Transcriptome Analysis.</a> J. Cancer. 1, 38-50 (2010).</li><li>Yehuda, R., Yang, R. K., Buchsbaum, M. S., Golier, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alterations+in+cortisol+negative+feedback+inhibition+as+examined+using+the+ACTH+response+to+cortisol+administration+in+PTSD.">Alterations in cortisol negative feedback inhibition as examined using the ACTH response to cortisol administration in PTSD.</a> Psychoneuroendocrinology. 31, 447-451 (2006).</li><li>Zhang, Q., Wu, J., Nguyen, A., Wang, B. D., He, P., Laurent, G. S., Rennert, O. M., Su, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Molecular+mechanism+underlying+differential+apoptosis+between+human+melanoma+cell+lines+UACC903+and+UACC903(+6)+revealed+by+mitochondria-focused+cDNA+microarrays.">Molecular mechanism underlying differential apoptosis between human melanoma cell lines UACC903 and UACC903(+6) revealed by mitochondria-focused cDNA microarrays.</a> Apoptosis. 13, 993-1004 (2008).</li></ol>

الإعلان عن أي تضارب في المصالح.

ويستند التشخيص على الأعراض من اضطراب ما بعد الصدمة النفسية وذكرت النفس (DSM IV) حسب الموضوع المحتملة. لا العلامات البيولوجية واضحة المعالم هو متاح حاليا للوصول إلى حالة المرضية في جسم المريض من المرضى PTSD محتملة. PTSD هو اضطراب تهدد الحياة التي أثارتها الأحداث المؤلمة والأعراض الرئيسية نفسية لا تزال موجودة في الحياة الناجي منذ شهور وحتى سنوات بعد أحداث الأولي. أكثر الأعراض بارزة ومستمرة في كشف المرضى الذين يعانون من اضطرابات ما بعد الصدمة هي hypervigilance، تأخر ردود الفعل المفاجئة المبالغ فيها 14 و 15 و 16 و حلا وسطا واضح في محور HPA. في البشر تظل هذه الأعراض، أو تظهر مع تأخير لمدة ثلاثة أشهر، بعد وقف الضغوطات صدمة 24. نموذجنا الحالي للدراسات العلامات البيولوجية لاضطراب ما بعد الصدمة توظف ضبط النفس والصدمات المتكررة الذيل لمدة ثلاثة أيام متواصلة (2-HR دورات 40، tailshocks مللي أمبير 2) - والذي لا مفر منه ذيل للصدمة نموذج (ITS) في الفئران وزنها 150 غرام. هذا النموذج لديه ITSثبت لتقليد إلى حد كبير في الفيزيولوجيا المرضية من اضطراب ما بعد الصدمة 17، 7، 4، 10. لقد التحقق مختبرنا ومختبرات أخرى أن نموذجها من التوتر في الفئران يدفع التعديلات السلوكية والعصبية الحيوية التي تشبه تلك التي وجدت في مواضيع PTSD 17، 7، 10، 9. على وجه التحديد، فإن هذه الفئران المتوترة يحمل (1) لتأخر الاستجابة ومبالغ فيها جفل تظهر بعد عدة أيام من وقف الضغوطات التي نظرا لحجم الوقت مضغوط من حياة الفئران مقارنة مع البشر، يتوافق مع تأخير شهر واحد إلى ثلاثة من أعراض في المرضى الذين يعانون اضطرابات ما بعد الصدمة (DSM-IV-TR PTSD Criterian D / E 13)، (2) تعزيز البلازما كورتيزون (CORT) لعدة أيام (10) عدة، مشيرا إلى حل وسط من محور hypothalamopituitary (HPA)، و (3) زيادة وزن الجسم المتخلفين بعد الضغوطات وقف، المقابلة لخلل في تنظيم الأيض من اضطرابات ما بعد الصدمة. ليس هناك أي دليل في الأدب أن الثعلب رائحة، والتعرض المفترس، أو يخشى ردود الفعل المفاجئة potentiated، exhiبت هذه الظواهر السلوكية الثابتة وneuroendocrinologic المرتبطة PTSD. وقد أظهرت الفئران التي عرضت لدورة واحدة الإجهاد (1DS) عابرة، ولكن ليس شذوذ الثابتة المعروضة من قبل الفئران 3DS (17) التجربة الحالية مقارنة ردود الفعل المفاجئة من الفئران و3DS 1DS 4 و 7 و 10 أيام بعد وقف الضغوطات. وشدد تتفق مع الأعمال السابقة، أظهرت الفئران مرتفعة القاعدية البلازما مستويات CORT في اول يوم عمل بعد الإجهاد 17. وكانت هذه المستويات CORT حساسة لعدد من الضغوطات التعرض مع مستويات أعلى في الفئران CORT 3DS من 1DS في الفئران. أما بالنسبة لردود الفعل المفاجئة، والفئران 1DS يحمل ردود الفعل المفاجئة المبالغ فيها 7 أيام الضغوطات آخر، في حين جفل التوعية فقط يصبح واضح 10 أيام آخر الضغوطات في الفئران 3DS. وهكذا، فإن ظهور استجابة المفاجئة المبالغ فيها بعد وقف الضغوطات ويبدو أن المتصل بعدد من التعرض الدورة الإجهاد. نموذج 3DS شدد يبدوتكون مفيدة لاكتساب نظرة ثاقبة في التعبير غيرت من المؤشرات الحيوية المرتبطة أعراض اضطراب ما بعد الصدمة والظواهر السلوكية مفتاح قياس المرتبطة توقيت بعد توقف التوتر. النتائج الجيني يقدم دليلا على قدم مبدأ لتطبيق rMNChip والمعلوماتية الحيوية لتحديد مسارات أدوات التفاضلية، والمؤشرات الحيوية الجينات والبروتينات، مما يسهل إلى حد كبير النظم البيولوجية دراسة وفهم الآليات الجزيئية الكامنة اضطرابات عصبية معقدة ومتعددة العوامل، بما في ذلك PTSD. بينما لدينا نموذج لا الخوض في الجوانب المعرفية والسلوكية أكثر تعقيدا من اضطرابات ما بعد الصدمة، نلاحظ أن تغيير أنماط النوم في نموذجها 1 تتوافق مع صعوبة في البقاء نائما والكوابيس واضطرابات ما بعد الصدمة من المرضى 11 PTSD DSM-IV-TR ( معايير D 13)، وأوجه القصور في الهروب / تجنب التعلم والتعلم من مهمة مشهي في نموذجها <sup&gt; 12 يتوافق مع تركيزات الفقراء والعجز ذكرى PTSD 5 (DSM-IV-TR PTSD معايير C 13). النموذج الحالي يرتبط بشكل جيد مع أعراض PTSD الرئيسية المميزة لويقدم نموذجا جيدا لربط المؤشرات الحيوية الطرفية من اضطرابات ما بعد الصدمة، والتي يمكن جمعها من المرضى، مع المؤشرات الحيوية، وسط الآلي، والتي لا 6.

biomarkers in an animal model for revealing neural, hematologic, and behavioral correlates of ptsd

تحديد المؤشرات الحيوية التي تمثل تطور الفيزيولوجيا المرضية من اضطراب ما بعد الصدمة (PTSD) أمر في غاية الاهمية، ليس فقط من أجل تشخيص موضوعي ولكن أيضا لتقييم الكفاءة العلاجية والقدرة على مواجهة الصدمات. يتم توجيه البحوث الجارية إلى تحديد المؤشرات الحيوية الجزيئية لاضطرابات ما بعد الصدمة، بما في ذلك البروتينات الصدمة الناجمة، transcriptomes، الفروق الجينية والوراثية جهري، وذلك باستخدام عينات بيولوجية من الدم الموضوعات &#39;، اللعاب، البول، وأنسجة المخ بعد الوفاة. ومع ذلك، فإن العلاقة بين هذه الجزيئات العلامات البيولوجية في عينات الطرفية أو بعد الوفاة لتغيير وظائف المخ المرتبطة الأعراض النفسية في اضطرابات ما بعد الصدمة لا تزال دون حل. هنا، نقدم نموذج حيواني من اضطرابات ما بعد الصدمة التي على حد سواء الدم المحيطي والمؤشرات الحيوية الدماغ الوسطى، فضلا عن النمط الظاهري السلوكية، يمكن جمعها وقياسها، وبالتالي توفير الارتباط اللازمة من المؤشرات الحيوية المركزي PTSD، وهي الآلية وpathognoولكن لا يمكن أن تجمع مونيك من الناس، مع المؤشرات الحيوية الظواهر السلوكية والطرفية، والتي يمكن. نموذجنا الحيوانية من PTSD توظف ضبط النفس والصدمات المتكررة الذيل لمدة ثلاثة أيام متواصلة - والذي لا مفر منه ذيل للصدمة نموذج (ITS) في الفئران. هذا النموذج ITS يحاكي الفيزيولوجيا المرضية من اضطراب ما بعد الصدمة 17، 7، 4، 10. تحققنا وغيرها أن يدفع نموذجها التعديلات السلوكية والعصبية الحيوية مشابهة لتلك الموجودة في مواضيع PTSD 17، 7، 10، 9. على وجه التحديد، فإن هذه الفئران المتوترة يحمل (1) لتأخر الاستجابة ومبالغ فيها جفل تظهر بعد عدة أيام من وقف الضغوطات التي نظرا لحجم الوقت مضغوط من حياة الفئران مقارنة مع البشر، يتوافق مع تأخير شهر واحد إلى ثلاثة من أعراض في المرضى الذين يعانون اضطرابات ما بعد الصدمة (DSM-IV-TR PTSD Criterian D / E 13)، (2) تعزيز البلازما كورتيزون (CORT) لعدة أيام، مشيرا إلى حل وسط من محور hypothalamopituitary (HPA)، و (3) بو المتخلفيندى زيادة الوزن بعد الإقلاع عن الضغوطات، مشيرا إلى خلل في تنظيم الأيض. والنماذج التجريبية المستخدمة لهذا النموذج هي: (1) نموذج العجز المكتسب في الفئران يعاير بواسطة قياس ردود الفعل المفاجئة الصوتية (ASR)، ورسم من كتلة الجسم، (2) تسليخ مجهري من الدماغ الفئران في المناطق ونوى، ( 3) انزيم مرتبط المناعي فحص (ELISA) لمستويات الدم من CORT، (4) التعبير الجيني لميكروأري بالإضافة إلى الأدوات المعلوماتية الحيوية ذات الصلة 18. هذا ميكروأري، يطلق عليها اسم rMNChip، يركز على جينات الميتوكوندريا النووي والميتوكوندريا ذات الصلة في الفئران وذلك لتتناول على وجه التحديد الطاقة الحيوية العصبية افترض أن تشارك في PTSD.

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Biomarkers in an Animal Model for Revealing Neural, Hematologic, and Behavioral Correlates of PTSD

نحن وصفا لنموذج الفئران من اضطراب ما بعد الصدمة (PTSD) أن يكشف عن التعديلات المستمرة في وظيفة الغدد الصم العصبية وتأخر طويل الأجل، استجابة الخوف المبالغ فيه، سمة من المرضى PTSD. النموذج الحيواني والأساليب المذكورة هنا هي مفيدة لربط المؤشرات الحيوية في الدماغ نوى، وهي الآلية ولكن لا يمكن أن يقاس في المرضى، مع المؤشرات الحيوية في خلايا الدم البيضاء الطرفية، والتي يمكن.

المؤشرات الحيوية في نموذج حيواني لكشف الاقتران العصبية، الدموية، والسلوكية للPTSD

Identification of biomarkers representing the evolution of the pathophysiology of Post Traumatic Stress Disorder (PTSD) is vitally important, not only for ...

biomarkers-an-animal-model-for-revealing-neural-hematologic

Research

JoVE Journal

Medicine

15.9K Views.  Uniformed Services University of the Health Sciences, Bethesda, Maryland. نحن وصفا لنموذج الفئران من اضطراب ما بعد الصدمة (PTSD) أن يكشف عن التعديلات المستمرة في وظيفة الغدد الصم العصبية وتأخر طويل الأجل، استجابة الخوف المبالغ فيه، سمة من المرضى PTSD. النموذج الحيواني والأساليب المذكورة هنا هي مفيدة لربط المؤشرات الحيوية في الدماغ نوى، و?...

Video: Biomarkers in an Animal Model for Revealing Neural, Hematologic, and Behavioral Correlates of PTSD

Use of Animal Model of Sepsis to Evaluate Novel Herbal Therapies

Sepsis refers to a systemic inflammatory response syndrome resulting from a microbial infection. It has been routinely simulated in animals by several techniques, including infusion of exogenous bacterial toxin (endotoxemia) or bacteria (bacteremia), as well as surgical perforation of the cecum by cecal ligation and puncture (CLP)1-3. CLP allows bacteria spillage and fecal contamination of the peritoneal cavity, mimicking the human clinical disease of perforated appendicitis or diverticulitis. The severity of sepsis, as reflected by the eventual mortality rates, can be controlled surgically by varying the size of the needle used for cecal puncture2. In animals, CLP induces similar, biphasic hemodynamic cardiovascular, metabolic, and immunological responses as observed during the clinical course of human sepsis3. Thus, the CLP model is considered as one of the most clinically relevant models for experimental sepsis1-3.
Various animal models have been used to elucidate the intricate mechanisms underlying the pathogenesis of experimental sepsis. The lethal consequence of sepsis is attributable partly to an excessive accumulation of early cytokines (such as TNF, IL-1 and IFN-&gamma;)4-6 and late proinflammatory mediators (e.g., HMGB1)7. Compared with early proinflammatory cytokines, late-acting mediators have a wider therapeutic window for clinical applications. For instance, delayed administration of HMGB1-neutralizing antibodies beginning 24 hours after CLP, still rescued mice from lethality8,9, establishing HMGB1 as a late mediator of lethal sepsis. The discovery of HMGB1 as a late-acting mediator has initiated a new field of investigation for the development of sepsis therapies using Traditional Chinese Herbal Medicine. In this paper, we describe a procedure of CLP-induced sepsis, and its usage in screening herbal medicine for HMGB1-targeting therapies.

Sepsis refers to a systemic inflammatory response syndrome resulting from a microbial infection, and can be simulated by a surgical technique termed cecal ligation and puncture (CLP). Here we describe a method to use CLP-induced animal model to screen medicinal herbs for therapeutic agents.

استخدام نموذج حيواني للتسمم لتقييم العلاجات العشبية رواية

Sepsis refers to a systemic inflammatory response syndrome resulting from a microbial infection. It has been routinely simulated in animals by several ...

An Isolated Working Heart System for Large Animal Models

Since its introduction in the late 19th century, the Langendorff isolated heart perfusion apparatus, and the subsequent development of the working heart model, have been invaluable tools for studying cardiovascular function and disease1-15. Although the Langendorff heart preparation can be used for any mammalian heart, most studies involving this apparatus use small animal models (e.g., mouse, rat, and rabbit) due to the increased complexity of systems for larger mammals1,3,11. One major difficulty is ensuring a constant coronary perfusion pressure over a range of different heart sizes &#8211; a key component of any experiment utilizing this device1,11. By replacing the classic hydrostatic afterload column with a centrifugal pump, the Langendorff working heart apparatus described below allows for easy adjustment and tight regulation of perfusion pressures, meaning the same set-up can be used for various species or heart sizes. Furthermore, this configuration can also seamlessly switch between constant pressure or constant flow during reperfusion, depending on the user&#8217;s preferences. The open nature of this setup, despite making temperature regulation more difficult than other designs, allows for easy collection of effluent and ventricular pressure-volume data.

Most studies involving the Langendorff apparatus use small animal models due to the increased complexity of systems for larger mammals. We describe a Langendorff system for large animal models that allows for use across a range of species, including humans, and relatively easy data acquisition.

نظام القلب العامل المعزولة لنماذج حيوانية كبيرة

Since its introduction in the late 19th century, the Langendorff isolated heart perfusion apparatus, and the subsequent development of the working heart ...

Bioluminescence Imaging of an Immunocompetent Animal Model for Glioblastoma

In contrast to commonly reported human glioma xenograft animal models, GL261 murine glioma xenografts recapitulate nearly all relevant clinical and histopathologic features of the human disease. When GL261 cells are implanted intracranially in syngeneic C57BL/6 mice, the model has the added advantage of maintaining an intact immune microenvironment. Stable expression of luciferase in GL261 cells allows non-invasive cost effective bioluminescence monitoring of intracranial tumor growth. We have recently demonstrated that luciferase expression in GL261 cells does not affect the tumor growth properties, tumor cell immunomodulatory cytokine expression, infiltration of immune cells into the tumor, or overall survival of animals bearing the intracranial tumor. Therefore, it appears that the GL261 luciferase glioma model can be useful in the study of novel chemotherapeutic and immunotherapeutic modalities. Here we report the technique for generating stable luciferase expression in GL261 cells and how to study the in vitro and in vivo growth of the tumor cells by bioluminescence imaging.

GL261 glioma cells provide a useful immunocompetent animal model of glioblastoma. The goals of this protocol are to demonstrate proper techniques for monitoring intracranial tumor growth using in vivo bioluminescence imaging, and to verify the utility of luciferase-modified GL261 cells for studying tumor immunology and immunotherapeutic approaches for treating glioblastoma.

التصوير تلألؤ بيولوجي لنموذج مناعيا الحيوان ورم أرومي دبقي

In contrast to commonly reported human glioma xenograft animal models, GL261 murine glioma xenografts recapitulate nearly all relevant clinical and ...

A Repetitive Concussive Head Injury Model in Mice

Despite the concussion/ mild traumatic brain injury (mTBI) being the most frequent occurrence of traumatic brain injury, there is still a lack of knowledge on the injury and its effects. To develop a better understanding of concussions, animals are often used because they provide a controlled, rigorous, and efficient model. Studies have adapted traditional animal models to perform mTBI to stimulate mild injury severity by changing the injury parameters. These models have been used because they can produce morphologically similar brain injuries to the clinical condition and provide a spectrum of injury severities. However, they are limited in their ability to present the identical features of injuries in patients. Using a traditional impact system, a repetitive concussive injury (rCHI) model can induce mild to moderate human-like concussion. The injury degree can be determined by measuring the period of loss of consciousness (LOC) with a sign of a transient termination of breathing. The rCHI model is beneficial to use for its accuracy and simplicity in determining mTBI effects and potential treatments.

Concussion presents the most common type of traumatic brain injury. Therefore, a repetitive concussive animal model, which replicates the important features of an injury in patients, may provide a means to study concussion in a rigorous, controlled, and efficient manner.

والمتكرر الارتجاج إصابات الرأس النموذجي في الفئران

Despite the concussion/ mild traumatic brain injury (mTBI) being the most frequent occurrence of traumatic brain injury, there is still a lack of ...

An Anesthesia, Surgery, and Harvest Method for the Evaluation of Transpedicular Screws Using an In Vivo Porcine Lumbar Spine Model

Pedicle screw fixation is the gold standard for the treatment of spinal diseases. However, many studies have reported the issue of loosening pedicle screws after spinal surgery, which is a serious concern. To address this problem, diverse types of pedicle screws have been examined to identify those with good fixation strength and osseointegration in spine bone. The porcine spine is a good alternative for the human spine in the evaluation of pedicle screws due to the anatomical size, mechanical characteristics, and cost. Although several studies have reported that pedicle screws are efficient in the porcine model, no study has described detailed protocols for the evaluation of a pedicle screw using the porcine model. Here, we describe a detailed method for evaluating transpedicular screws using an in vivo porcine lumbar spine model. The technical details for anesthesia, spine surgery, and harvest provided here will facilitate with the evaluation of the transpedicular screw fixation model.

An Anesthesia, Surgery, and Harvest Method for the Evaluation of Transpedicular Screws Using an In Vivo Porcine Lumbar Spine Model

Here, we introduce a method to evaluate transpedicular screws by using an in vivo porcine lumbar spine model.

التخدير، والجراحة، وطريقة الحصاد لتقييم مسامير ترانسبديكولار باستخدام<em&gt; في فيفو</em&gt; الخنزير القطني العمود الفقري نموذج

Pedicle screw fixation is the gold standard for the treatment of spinal diseases. However, many studies have reported the issue of loosening pedicle ...

A Chronic Cardiac Ischemia Model in Swine Using an Ameroid Constrictor

Cardiovascular disease remains the number one cause of mortality in the United States. There are numerous approaches to treating these diseases, but regardless of the approach, an in vivo model is needed to test each treatment. The pig is one of the most used large animal models for cardiovascular disease. Its heart is very similar in anatomy and function to that of a human. The ameroid placement technique creates an ischemic area of the heart, which has many useful applications in studying myocardial infarction. This model has been used for surgical research, pharmaceutical studies, imaging techniques, and cell therapies.
There are several ways of inducing an ischemic area in the heart. Each has its advantages and disadvantages, but the placement of an ameroid constrictor remains the most widely used technique. The main advantages to using the ameroid are its prevalence in existing research, its availability in various sizes to accommodate the anatomy and size of the vessel to be constricted, the surgery is a relatively simple procedure, and the post-operative monitoring is minimal, since there are no external devices to maintain. This paper provides a detailed overview of the proper technique for the placement of the ameroid constrictor.

The purpose of this protocol is to demonstrate the placement of a delayed constricting device (an ameroid constrictor) around a coronary artery in a swine model. This device creates an ischemic area of the heart that is useful for studying new diagnostic imaging techniques and new methods of treatment.

نموذج الاسكيمية القلب مزمنة في الخنازير باستخدام العاصرة أميرويد

Cardiovascular disease remains the number one cause of mortality in the United States. There are numerous approaches to treating these diseases, but ...

Assessment of Plasma Coagulation on Liver Tissue in a Large Animal Model In Vivo

Plasma coagulation as a form of electrocautery is used in liver surgery for decades to seal the large liver cut surface after major hepatectomy to prevent hemorrhages at a later stage. The exact effects of plasma coagulation on liver tissue are only poorly examined. In our porcine model, the coagulation effects can be examined close to the clinical application. A combined laser Doppler flowmeter and spectrophotometer documents microcirculation changes during coagulation at 8 mm tissue depth noninvasively, providing quantifiable information about hemostasis beyond the subjective clinical impression. The temperature at coagulation site is assessed with an infrared thermometer prior and post coagulation and with a thermographic camera during coagulation, a measurement of the gas beam temperature is not possible due to the upper threshold of the devices. The depth of coagulation is measured microscopically on hematoxylin/eosin stained sections after calibration with an object micrometer and gives an exact information about the power setting-coagulation depth-relation. The sealing effect is examined on the bile ducts as it is not possible for a plasma coagulator to seal larger blood vessels. Burst pressure experiments are carried out on explanted organs to rule out blood pressure related effects.

Assessment of Plasma Coagulation on Liver Tissue in a Large Animal Model In Vivo

Here we present a protocol to experimentally assess plasma coagulation in liver tissue in vivo. In a porcine model, microcirculation is examined by laser Doppler, coagulation depth is measured histologically, temperature at coagulation site by infrared thermometer and thermographic camera, and duct sealing effect is documented by burst pressure experiments.

تقييم تخثر البلازما في أنسجة الكبد في نموذج حيوانات كبيرة في فيفو

Plasma coagulation as a form of electrocautery is used in liver surgery for decades to seal the large liver cut surface after major hepatectomy to prevent ...

Intra-Operative Neural Monitoring of Thyroid Surgery in a Porcine Model

Intraoperative injury to the recurrent laryngeal nerve (RLN) can cause vocal cord paralysis, which interferes with speech and can potentially interfere with breathing. In recent years, intraoperative neural monitoring (IONM) has been widely adapted as an adjunct technique to localize the RLN, detect RLN injury, and predict vocal cord function during the operations. Many studies have also used animal models to investigate new applications of IONM technology and to develop reliable strategies for preventing intraoperative RLN injury. The aim of this article is to introduce a standard protocol for using a porcine model in IONM research. The article demonstrates the procedures for inducing general anesthesia, performing tracheal intubation, and experimental design to investigate the electrophysiological characteristics of RLN injuries. Applications of this protocol can improve overall efficacy in implementing the 3R principle (replacement, reduction and refinement) in porcine IONM studies.

This study aims to develop a standard protocol of intra-operative neural monitoring of thyroid surgery in a porcine model. Here, we present a protocol to demonstrate general anesthesia, to compare different types of electrodes, and to investigate the electrophysiological characteristics of the normal and injured recurrent laryngeal nerves.

رصد العصبية داخل منطوق جراحة الغدة الدرقية في نموذج الخنزير

Intraoperative injury to the recurrent laryngeal nerve (RLN) can cause vocal cord paralysis, which interferes with speech and can potentially interfere ...

Isometric Contractility Measurement of the Mouse Mesenteric Artery Using Wire Myography

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and drugs. It is widely used in many studies on the physiological functions of vascular smooth muscle, the pathogenesis of vascular diseases such as hypertension, and the development of smooth muscle relaxant drugs. The mouse is a widely used model animal with a large pool of disease models and genetically modified strains. We introduced this method to measure the isometric contraction of mouse mesenteric artery in detail. A 1.4-mm segment of mouse mesenteric resistance artery was isolated and mounted on a myograph chamber by passing two steel wires through its lumen. After equilibration and normalization steps, the vessel segment was potentiated by a high-K+ solution twice prior to the contraction assay. As an example of the application of this method in drug development, we measured the relaxant effect of a novel natural substance, neoliensinine, isolated from a Chinese herb, embryos of the lotus seed (Nelumbo nucifera Gaertn.) on mouse mesenteric arteries. The vessel segments mounted on the myograph chamber were stimulated with a high-K+ solution. When the force tension reached a stable sustained phase, cumulative doses of neoliensinine were added to the chamber. We found that neoliensinine had a dose-dependent relaxant effect on smooth muscle contraction, thus suggesting that it bears potential activity against hypertension. In addition, as the vessel segment can survive at least 4 hours after mounting and maintain contractility induced by the high-K+ solution for many times, we suggest that the wire myograph system may be used for the time-consuming process of drug screening.

The wire myograph technique is used to investigate vascular smooth muscle functions and screen new drugs. We report a detailed protocol for measuring the isometric contractility of the mouse mesenteric artery and for screening new relaxants of vascular smooth muscle.

متساوي القياس كونتراكتيليتي القياس الشريان المساريقي العلوي الماوس باستخدام أسلاك ميوجرافي

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and ...

Manufacture of a Multi-Purpose Low-Cost Animal Bench-Model for Teaching Tracheostomy

Tracheostomy is one of the most frequent procedures, performed through various techniques in the intensive care unit and emergency situations. Despite this, there is a lack of training on this procedure that affects its outcome, which is also dependent on operator's dexterity. Here, we take the specific training and simulation into consideration. This article aims to describe every step of the manufacture of a new multi-purpose low-cost animal bench-model, with the support of video and images, and to obtain an opinion about the quality of this model by administering a questionnaire to professionals with experience in the procedures. 
Ten experts in the technique were enrolled. The model scored an average of 3.45/5 for its anatomical realism; 4.75/5 for its usefulness as a training tool for simulation courses and assessments. The time necessary to build the model was 15 minutes, and the cost amounted to 10&#8364;. The animal bench-model was considered a very useful simulator for tracheostomy training and assessments. Therefore, it could be used as a tool for medical courses and residencies.

This article illustrates every step of the manufacture of a new multi-purpose low-cost animal bench-model for subglottic airway access management. All the procedures are shown in the video. The model's realism and its suitability for training the given clinical maneuvers were assessed by independent senior otolaryngologists and anesthesiologists.

تصنيع متعددة الأغراض الحيوانية منخفضه التكلفة مقاعد البدلاء-نموذج لتعليم فغر الرغامي

Tracheostomy is one of the most frequent procedures, performed through various techniques in the intensive care unit and emergency situations. Despite ...