Diese Forschung wurde durch die Interne Research Program der NIH, National Institute on Aging und der Baltimore Longitudinal Study on Aging. Ein Teil dieser Unterstützung war durch eine F &amp; E-Vertrag mit MedStar Research Institute. Standardprotokoll und technischen Know-how wurde von ATCOR Verfügung gestellt.

1. Verfahren <ol><li> Öffnen Sie die Software über die Verknüpfung auf dem Windows-Desktop durch einen Doppelklick auf das Symbol. </li><li> Klicken Sie auf Patient, um den Patientenbildschirm aktivieren. </li><li> Um einen neuen Patienten in die Datenbank einzugeben, klicken Sie auf die Schaltfläche Neu in der Patientensuchbereich, und klicken Sie auf die Schaltfläche Ja, um zu bestätigen Sie möchten, um einen neuen Patienten geben. </li><li> Geben Sie die Patientendaten wie Name, Vorname, Geburtsdatum und Geschlecht. Klicken Sie auf die Schaltfläche Speichern, um zum nächsten Schritt zu gelangen. </li><li> Klicken Sie auf die PWA oder PWV-Taste, um die Messung durchzuführen. Wenn nur eine dieser Betriebsarten zur Verfügung steht, gibt es keine Notwendigkeit, auf den Button klicken, wird einfach auf die Studie Bildschirm zu gelangen. </li></ol> 2. Zentrale Blutdruckmessung mit Pulswellenanalyse (PWA) <ol><li> Klicken Sie auf die Schaltfläche, um Studien Studie Parameter eingeben. Geben Sie die Arm-Blutdruckmessgerät von einem kalibrierten und alle anderen Details, die Sie aufnehmen möchten übernommen. </li><li> Click auf dem Capture-Daten-Taste, um mit einem Mess fortzufahren. Bringen Sie die drei EKG-Elektroden und Leitungen zu dem Patienten in eine modifizierte Blei-II-Konfiguration oder mit Gliedmaßen des Patienten, wie auf den Leitungen angezeigt. </li><li> Tasten Sie Radialarterie des Patienten. Dies beruht auf der seitlichen des Handgelenks unmittelbar oberhalb des Handgelenks nahe der Basis des Daumens. Drücken Sie vorsichtig die Schlagader gegen den darunter liegenden Knochen mit dem Mittel-und Zeigefinger. </li><li> Legen Sie das Tonometer über den stärksten Impuls Punkt. Drücken Sie vorsichtig das Tonometer nach unten, bis Sie eine konsistente Druckwellenform auf der Datenerfassung Bildschirm angezeigt werden. </li><li> Wenn Auto Capture aktiviert ist (siehe Hinweis unten), wird das System die Messung automatisch speichern. Um die Messung manuell speichern für Analyse, drücken Sie die Leertaste auf der Tastatur (oder betätigen Sie den Fußschalter, falls verwendet). </li><li> Wenn eine Wiederholungsmessung wird mit den gleichen Studienparameter erforderlich, klicken Sie auf die Schaltfläche Wiederholen, um zum Aufnahme zurückDatenanzeige und Messung wiederholen wie in Schritten von 2,4 bis 2,5 oben beschrieben. </li><li> Um eine Messung an einem neuen Patienten durchzuführen, klicken Sie auf die Schaltfläche Patient, und kehren Sie zum obigen Schritt 1.3. </li></ol> 3. Gefäßsteifigkeit Messung mit Pulswellengeschwindigkeit (PWV) <ol><li> Klicken Sie auf die Schaltfläche, um Studien Studie Parameter eingeben. </li><li> Geben Sie Arm-Blutdruckmessgerät von einem kalibrierten genommen Geben Sie den Abstand für die distale (suprasternalen Kerbe Femoralispuls) gemessen und proximale (suprasternalen Kerbe Carotispuls) Websites. Medikamente, Notizen und Betreiber Felder eingegeben werden können, wenn gewünscht </li><li> Klicken Sie auf die Schaltfläche Capture, um mit der Messung fortfahren. </li><li> Stellen Sie sicher, das EKG-Signal ist von akzeptabler Qualität. </li><li> Tasten Sie den Puls der Halsschlagader. Dieser wird zwischen den Kehlkopf und die Kopfnicker im Hals. Es kann durch Drücken der Muskeln an der Seite und Drücken der Arterie gegen den Kehlkopf zu spüren. </li><li&gt; Legen Sie das Tonometer auf die Halsschlagader und drücken Sie vorsichtig den Tonometer nach unten, bis Sie eine konsistente Druckwellenform auf dem Bildschirm angezeigt Datenerfassung zu erhalten. </li><li> Wenn Sie ein Minimum von 13 Sek. konsequente Wellenformen haben, klicken Sie auf die OK-Taste oder (drücken Sie den Fußschalter, falls verwendet). </li><li> Tasten Sie die Oberschenkelarterie Puls. Dies wird über den ventralen Oberschenkel auf halbem Weg zwischen der Symphyse und Spina iliaca anterior superior befindet. </li><li> Legen Sie das Tonometer auf der Oberschenkelarterie und drücken Sie vorsichtig den Tonometer nach unten, bis Sie eine konsistente Druckwellenform auf dem Aufnahmebildschirm angezeigt bekommen. Wenn Sie ein Minimum von 13 Sek. konsequente Wellenformen haben, klicken Sie auf die OK-Taste (oder drücken Sie die Taste auf dem Fußschalter, falls verwendet). </li><li> Der Bericht (n) kann nun überprüft werden. Diese Messungen werden typischerweise in dreifacher Ausführung durchgeführt. Wenn der Benutzer die PWV zwischen Halsschlagadern und radiale messen möchte, würde diese Schritte nur mit der Ausnahme, dass anstelle der Messung an der f wiederholt werdenemoral Arterie, würde der Benutzer den Tonometer an der radialen Arterie zu platzieren. Um eine Messung an einem neuen Patienten durchzuführen, klicken Sie auf die Schaltfläche Study und wiederholen Sie den Vorgang, oder verwenden Sie die Suchfunktion, um nach einer vorhandenen Patienten suchen. </li></ol> 4. Schließen <ol><li> Die Software speichert automatisch alle Berichte. Um die Software zu schließen, klicken Sie auf die System aus dem Hauptmenü, und klicken Sie auf Beenden. Legen Sie das Tonometer in dem Modul Fach für die Lagerung. </li></ol>

<ol>
	<li>Najjar, S. S., Scuteri, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pulse+wave+velocity+is+an+independent+predictor+of+the+longitudinal+increase+in+systolic+blood+pressure+and+of+incident+hypertension+in+the+Baltimore+Longitudinal+Study+of+Aging.">Pulse wave velocity is an independent predictor of the longitudinal increase in systolic blood pressure and of incident hypertension in the Baltimore Longitudinal Study of Aging.</a> J. Am. Coll. Cardiol. 51 (14), 1377-1383 (2008).</li><li>Doonan, R. J., Scheffler, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Altered+arterial+stiffness+and+subendocardial+viability+ratio+in+young+healthy+light+smokers+after+acute+exercise.">Altered arterial stiffness and subendocardial viability ratio in young healthy light smokers after acute exercise.</a> PloS one. 6 (10), (2011).</li><li>Laurent, S., Cockcroft, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Expert+consensus+document+on+arterial+stiffness:+methodological+issues+and+clinical+applications.">Expert consensus document on arterial stiffness: methodological issues and clinical applications.</a> Eur. Heart J. 27 (21), 2588-2605 (2006).</li><li>Mitchell, G. F., Hwang, S. -. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Arterial+stiffness+and+cardiovascular+events:+the+Framingham+Heart+Study.">Arterial stiffness and cardiovascular events: the Framingham Heart Study.</a> Circulation. 121 (4), 505-511 (2010).</li><li>Abbatecola, A. M., Chiodini, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pulse+wave+velocity+is+associated+with+muscle+mass+decline:+Health+ABC+study.">Pulse wave velocity is associated with muscle mass decline: Health ABC study.</a> Age. , (2011).</li><li>Watson, N. L., Sutton-Tyrrell, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Arterial+stiffness+and+gait+speed+in+older+adults+with+and+without+peripheral+arterial+disease.">Arterial stiffness and gait speed in older adults with and without peripheral arterial disease.</a> Am. J. Hypertens. 24 (1), 90-95 (2011).</li><li>Mackenzie, I. S., Wilkinson, I. B., Cockcroft, J. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessment+of+arterial+stiffness+in+clinical+practice.">Assessment of arterial stiffness in clinical practice.</a> QJM. 95 (2), 67-74 (2002).</li><li>O'Rourke, M. F., Pauca, A., Jiang, X. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pulse+wave+analysis.">Pulse wave analysis.</a> Br. J. Clin. Pharmacol. 51 (6), 507-522 (2001).</li><li>Stoner, L., Young, J. M., Fryer, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessments+of+arterial+stiffness+and+endothelial+function+using+pulse+wave+analysis.">Assessments of arterial stiffness and endothelial function using pulse wave analysis.</a> Int. J. Vasc. Med. 2012, 903107 (2012).</li><li>Farro, I., Bia, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pulse+wave+velocity+as+marker+of+preclinical+arterial+disease:+reference+levels+in+a+uruguayan+population+considering+wave+detection+algorithms,+path+lengths,+aging,+and+blood+pressure.">Pulse wave velocity as marker of preclinical arterial disease: reference levels in a uruguayan population considering wave detection algorithms, path lengths, aging, and blood pressure.</a> Int. J. Hypertens. 2012, (2012).</li><li>Lakatta, E. G., Wang, M., Najjar, 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=Arterial+aging+and+subclinical+arterial+disease+are+fundamentally+intertwined+at+macroscopic+and+molecular+levels.">Arterial aging and subclinical arterial disease are fundamentally intertwined at macroscopic and molecular levels.</a> Med. Clin. N. Am. 93 (3), 583-604 (2009).</li><li>Ambrose, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Clinical Manual (CVMS) Rev. 2, 1-51 (2011).</li><li>. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reference+Values+for+Arterial+Stiffness'+Collaboration+Determinants+of+pulse+wave+velocity+in+healthy+people+and+in+the+presence+of+cardiovascular+risk+factors:+'establishing+normal+and+reference+values.">Reference Values for Arterial Stiffness' Collaboration Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors: 'establishing normal and reference values.</a> Eur. Heart J. 31 (19), 2338-2350 (2010).</li><li>van Bortel, L. M., Laurent, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Expert+consensus+document+on+the+measurement+of+aortic+stiffness+in+daily+practice+using+carotid-femoral+pulse+wave+velocity.">Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity.</a> J. Hypertens. 30 (3), 445-448 (2012).</li><li>Scuteri, A., Brancati, A., Gianni, W., Assisi, A., Volpe, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Arterial+stiffness+is+an+independent+risk+factor+for+cognitive+impairment+in+the+elderly:+a+pilot+study.">Arterial stiffness is an independent risk factor for cognitive impairment in the elderly: a pilot study.</a> J. Hypertens. 23 (6), 1211 (2005).</li><li>Khoshdel, A. R., Carney, S. L., Nair, B. R., Gillies, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Better+management+of+cardiovascular+diseases+by+pulse+wave+velocity:+combining+clinical+practice+with+clinical+research+using+evidence-based+medicine.">Better management of cardiovascular diseases by pulse wave velocity: combining clinical practice with clinical research using evidence-based medicine.</a> Clin. Med. Res. 5 (1), 45-52 (2007).</li></ol>

Die Autoren erklären, dass sie keine finanziellen Interessen konkurrieren. Die Autoren erhalten Unterstützung bei der Protokollbeschreibung und die Leistung der Studie aus SphygmoCor die diese beschriebene Produkt herstellt.

Die Messung der Pulswellengeschwindigkeit (PWV) ist ein nicht-invasives Verfahren zum Analysieren zentralen arteriellen Steifigkeit in einer relativ einfachen und reproduzierbaren Weise 3. Um zu beurteilen, PWV, die Halsschlagader (als Ersatz für die absteigende Aorta) und Schenkelpulswellenformen werden mit einem High-Fidelity-Tonometer erworben, die Zeitverzögerung bei der Pulswelle der Ankunft in der zwischen den beiden Standorten wird geschätzt, Referenzierung auf eine gleichzeitig aufgezeichneten EKG-...

A correction was made to <a href="http://www.jove.com/video/50817">Pulse Wave Velocity Testing in the Baltimore Longitudinal Study of Aging</a>. There was an error with the author, Majd AlGhatrif's, name. The author's name has been corrected to:
Majd AlGhatrif
instead of:
Majd al Ghatrif

A correction to the author list has been made for article <a href="http://www.jove.com/video/50817">Pulse Wave Velocity Testing in the Baltimore Longitudinal Study of Aging</a>.

Erratum: Pulse Wave Velocity Testing in the Baltimore Longitudinal Study of Aging

Pulswellengeschwindigkeit (PWV) wird als der Goldstandard in der Beurteilung der arteriellen Steifigkeit 2 angesehen. Während klinisch nicht in den Vereinigten Staaten verwendet wurde validiert und in Europa 3 in der klinischen Einstellungen verwendet. Änderungen in der PWV haben mit kardiovaskulären Risikofaktoren wie Bluthochdruck, Übergewicht, gestörter Glukosetoleranz, Dyslipidämie und korreliert. Höhere Steifigkeit der Aorta wurde mit einem erhöhten Risiko für ein erstes kardiovaskuläres Ereignis 4, Muskelmasse Rückgang 5, und langsamer Gehgeschwindigkeit bei Patienten mit peripheren arteriellen Verschlusskrankheit 6 in Verbindung gebracht. Beurteilung der PWV durch Analysieren der Geschwindigkeit, mit der ein Impuls mit Blut fließt von der Halsschlagader zu der Femoralarterie 7 erreicht. Es ist ein relativ einfaches Verfahren mit hoch reproduzierbare Ergebnisse. Fortschritte in der Technologie weiter, um das Verfahren zu vereinfachen, wodurch Betreiber Abhängigkeit und die Verringerung der Menge an Zeit für die erforderlichePrüfung. Die in unserem Labor verwendete System erzeugt durch SphygmoCorand verwendet ein EKG und einen High-Fidelity-Tonometer-Wellenformen aus der Carotis und Femoralispulse erwerben. Die Software analysiert dann diese Variablen, um die Geschwindigkeit zu bestimmen, um 1) die Schätzung der Zeit, die die Pulswelle braucht, um zwischen der femoralen und Halsschlagstellen durch Bezugnahme auf den Zeitpunkt der Ankunft der Druckwelle an jedem Arterienstelle relativ zu den elektrokardiographischen Wellenformen 2 Reise) Aufteilen der gemessene Abstand zwischen den beiden Stellen durch die geschätzte Zeit. Je näher die Messstellen zusammen, desto ungenauer die PWV, wodurch die Anwendung dieses Verfahrens in größere Gefäße wie den femoralen und Halsschlagadern. Zusätzlich zur Bestimmung PWV kann das System den Druck in der Aorta ascendens durch Anwenden einer Übertragungsfunktion auf das durch die radiale Impuls 8, der dem &quot;zentralen Druck&quot; und der Druck erzeugte Wellenform zu berechnen, die am unmittelbarsten Auswirkungen das Herz bei der Ausstoß. Diese Informationen können bei der Beurteilung der Auswirkungen des arteriellen Systems auf der linken Herzkammer in einer zuverlässigen und nicht-invasive Weise 9 unterstützen. Alternative Techniken für die Untersuchung von Gefäßsteifigkeit verwendet werden, wie Halsschlag Dehnbarkeit über Echoverfolgung, erfordern ein hohes Maß an technischem Know-how und sind zeitaufwendiger als der PWV. Echofolger auch allgemein verwendet Video-Bildanalyse und daher die Genauigkeit dieser Messungen sind 3 begrenzt. Andere Techniken zum Untersuchen Gefäßveränderungen eine Bewertung der Karotis-Intima-Media-Dicke (IMT), die Ergebnisse genauer Progression atherosklerotischer bezogen, obwohl die Querschnitt-und Quer Bilder erhalten kann eine grobe Annäherung der Carotis Elastanz bereitzustellen bietet. Diese Methode wird jedoch von einigen der gleichen Einschränkungen wie die oben beschriebenen Studien Dehnbarkeit geplagt. Als Forscher weiterhin auf die Rolle, die arterielle Steifheit spielt in verschiedenen Krankheitsstadien betrachten,PWV-Messung wird wahrscheinlich weiterhin eine quantitative und reproduzierbare Surrogatendpunkt ist.

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pulse wave velocity testing in the baltimore longitudinal study of aging

Karotis-Oberschenkel-Pulswellengeschwindigkeit gilt als der Goldstandard für die Messung der zentralen arteriellen Steifigkeit durch nicht-invasive Methoden 1 erhalten. Themen werden in Rückenlage gebracht und man ließ sie leise und für mindestens 10 min vor dem Beginn der Prüfung ruhen. Die richtige Manschettengröße ausgewählt ist, und eine Blutdruck wird mittels eines oszillometrischen Vorrichtung erhalten. Sobald ein Ruheblutdruck erhalten worden ist, sind Druckwellenformen von den rechten Femur und rechte Arteria carotis communis erworben. Das System berechnet dann automatisch die Impulslaufzeit zwischen diesen beiden Stellen (mit der Halsschlagader als Surrogat für die absteigende Aorta). Körperoberflächenmessungen werden verwendet, um den Abstand von der Pulswelle zwischen den beiden Messstellen Paar zu bestimmen. Dieser Abstand wird dann durch die Pulswellenlaufzeit, was zur Pulswellengeschwindigkeit geteilt. Die Messungen werden dreifach durchgeführt und der Mittelwert für den Analbereich verwendetlyse.

<html><img alt="Tabelle 1" fo:content-width="5in" fo:src="/files/ftp_upload/50817/50817table1highres.jpg" src="/files/ftp_upload/50817/50817table1.jpg" /> Tabelle 1. PWV Ergebnisse werden in Meter pro Sekunde produziert. Bei gesunden Probanden können diese Geschwindigkeiten von durchschnittlich 6,2 m / s (bei ​​Personen unter 30) auf 10,9 m / s liegen (in den Fächern 70 und älter). Diese Werte wurden in dem Artikel &quot;Determinanten der Pulswellengesch...

Watch this Scientific Journal Video about Pulse Wave Velocity Testing in the Baltimore Longitudinal Study of Aging at JoVE.com

Pulse Wave Velocity Testing in the Baltimore Longitudinal Study of Aging

Die Pulswellengeschwindigkeit (PWV) Messung beurteilt arteriellen Steifigkeit durch eine Tonometrie-basierte System, das die Geschwindigkeit, mit der arteriellen Druckwelle entlang der arteriellen Baum, in der Regel in etwa der Zeit, die es dauert, diese Welle von der absteigenden Aorta (mit der Halsschlag reisen misst Arterie als Surrogat) an der Oberschenkelarterie. Karotis-Oberschenkel PWV erhöht zwei-bis über die dreifache Lebensdauer Erwachsenen.

Pulswellengeschwindigkeit Testing in der Baltimore Longitudinal Study of Aging

Carotid-femoral pulse wave velocity is considered the gold standard for measurements of central arterial stiffness obtained through noninvasive ...

pulse-wave-velocity-testing-baltimore-longitudinal-study

Research

Education

JoVE Core

JoVE Journal

Nursing

Medicine

Unit 1

Vital Signs: Pulse

SCIENTISTS IN ACTION

17.0K Aufrufe.  National Institute of Aging.  Die Pulswellengeschwindigkeit (PWV) Messung beurteilt arteriellen Steifigkeit durch eine Tonometrie-basierte System, das die Geschwindigkeit, mit der arteriellen Druckwelle entlang der arteriellen Baum, in der Regel in etwa der Zeit, die es dauert, diese Welle von der absteigenden Aorta (mit der Halsschlag reisen misst Arterie als Surrogat) an der Oberschenkelarterie. Karotis-Oberschenkel PWV erhöht zwei-bis über die dreifache Lebensdauer Erwachsenen. 

Serie: Pulse Wave Velocity Testing in the Baltimore Longitudinal Study of Aging

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

Identification of biomarkers representing the evolution of the pathophysiology of Post Traumatic Stress Disorder (PTSD) is vitally important, not only for objective diagnosis but also for the evaluation of therapeutic efficacy and resilience to trauma. Ongoing research is directed at identifying molecular biomarkers for PTSD, including traumatic stress induced proteins, transcriptomes, genomic variances and genetic modulators, using biologic samples from subjects' blood, saliva, urine, and postmortem brain tissues. However, the correlation of these biomarker molecules in peripheral or postmortem samples to altered brain functions associated with psychiatric symptoms in PTSD remains unresolved. Here, we present an animal model of PTSD in which both peripheral blood and central brain biomarkers, as well as behavioral phenotype, can be collected and measured, thus providing the needed correlation of the central biomarkers of PTSD, which are mechanistic and pathognomonic but cannot be collected from people, with the peripheral biomarkers and behavioral phenotypes, which can.
Our animal model of PTSD employs restraint and tail shocks repeated for three continuous days - the inescapable tail-shock model (ITS) in rats. This ITS model mimics the pathophysiology of PTSD 17, 7, 4, 10. We and others have verified that the ITS model induces behavioral and neurobiological alterations similar to those found in PTSD subjects 17, 7, 10, 9. Specifically, these stressed rats exhibit (1) a delayed and exaggerated startle response appearing several days after stressor cessation, which given the compressed time scale of the rat's life compared to a humans, corresponds to the one to three months delay of symptoms in PTSD patients (DSM-IV-TR PTSD Criterian D/E 13), (2) enhanced plasma corticosterone (CORT) for several days, indicating compromise of the hypothalamopituitary axis (HPA), and (3) retarded body weight gain after stressor cessation, indicating dysfunction of metabolic regulation.
The experimental paradigms employed for this model are: (1) a learned helplessness paradigm in the rat assayed by measurement of acoustic startle response (ASR) and a charting of body mass; (2) microdissection of the rat brain into regions and nuclei; (3) enzyme-linked immunosorbent assay (ELISA) for blood levels of CORT; (4) a gene expression microarray plus related bioinformatics tools 18. This microarray, dubbed rMNChip, focuses on mitochondrial and mitochondria-related nuclear genes in the rat so as to specifically address the neuronal bioenergetics hypothesized to be involved in PTSD.

We describe a rat model of post traumatic stress disorder (PTSD) that reveals the persistent alterations in neuroendocrine function and the delayed long-term, exaggerated fear response, characteristic of PTSD patients. The animal model and methods described here are useful for correlating biomarkers in brain nuclei, which are mechanistic but cannot be measured in patients, with biomarkers in peripheral white blood cells, which can.

Biomarker in einem Tiermodell für die Aufdeckung Neural, hämatologischen und Behavioral Korrelate der PTSD

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

Forschung

Medizin

Orthotopic Aortic Transplantation in Mice for the Study of Vascular Disease

Vascular procedures involving anastomoses in the mouse are generally thought to be difficult and highly dependent on the skill of the individual surgeon. This is largely true, but there are a number of important principles that can reduce the difficulty of these procedures and enhance reproducibility. Orthotopic aortic transplantation is an excellent procedure in which to learn these principles because it involves only two end-to-end anastomoses, but requires good suturing technique and handling of the vessels for consistent success. This procedure begins with the procurement of a length of abdominal aorta from a donor animal, followed by division of the native aorta in the recipient. The procured aorta is then placed between the divided ends of the recipient aorta and sutured into place using end-to-end anastomoses. To accomplish this objective successfully requires a high degree of concentration, good tools, a steady hand, and an appreciation of how easily the vasculature of a mouse can be damaged, resulting in thrombosis. Learning these important principles is what occupies most of the beginner's time when learning microsurgery in small rodents. Throughout this protocol, we refer to these important points. This model can be used to study vascular disease in a variety of different experimental systems1-8. In the context shown here, it is most often used for the study of post-transplant vascular disease, a common long-term complication of solid organ transplantation in which intimal hyperplasia occurs within the allograft. The primary advantage of the model is that it facilitates quantitative morphometric analyses and the transplanted vessel lies contiguous to the endogenous vessel, which can serve as an additional control9. The technique shown here is most often used for mice weighing 18-25 grams. We have accumulated most of our experience using the C57BL/6J, BALB/cJ, and C3H/HeJ strains.

We describe a technique in which a section of the abdominal aorta from a mouse is transplanted orthotopically to just below the renal arteries in an allogeneic or syngeneic recipient. This technique can be useful in studies in which transplantation of large arteries of uniform size is deemed advantageous.

Orthotopen Aortic Transplantation in Mäuse für das Studium der Vascular Disease

Vascular procedures involving anastomoses in the mouse are generally thought to be difficult and highly dependent on the skill of the individual surgeon. ...

Testing the Efficacy of Pharmacological Agents in a Pericardial Target Delivery Model in the Swine

To date, many pharmacological agents used to treat or prevent arrhythmias in open-heart cases create undesired systemic side effects. For example, antiarrhythmic drugs administered intravenously can produce drops in systemic pressure in the already compromised cardiac patient. While performing open-heart procedures, surgeons will often either create a small port or form a pericardial cradle to create suitable fields for operation. This access yields opportunities for target pharmacological delivery (antiarrhythmic or ischemic preconditioning agents) directly to the myocardial tissue without undesired side effects.
We have developed a swine model for testing pharmacological agents for target delivery within the pericardial fluid. While fully anesthetized, each animal was instrumented with a Swan-Ganz catheter as well as left and right ventricle pressure catheters, and pacing leads were placed in the right atrial appendage and the right ventricle. A medial sternotomy was then performed and a pericardial access cradle was created; a plunge pacing lead was placed in the left atrial appendage and a bipolar pacing lead was placed in the left ventricle. Utilizing a programmer and a cardiac mapping system, the refractory period of the atrioventricular node (AVN), atria and ventricles was determined. In addition, atrial fibrillation (AF) induction was produced utilizing a Grass stimulator and time in AF was observed. These measurements were performed prior to treatment, as well as 30 min&#160;and 60 min&#160;after pericardial treatment. Additional time points were added for selected studies. The heart was then cardiopleged and reanimated in a four chamber working mode. Pressure measurements and function were recorded for 1 hr after reanimation. This treatment strategy model allowed us to observe the effects of pharmacological agents that may decrease the incidence of cardiac arrhythmias and/or ischemic damage, during and after open-heart surgery.

We have developed a swine model for the target delivery of pharmacological agents within the pericardial space/fluid. Using this approach, the relative benefits of administered agents on induced atrial fibrillation, relative refractory periods and/or ischemic protection can be investigated.

Prüfung der Wirksamkeit von pharmakologischen Wirkstoffen in einem Pericardial Ziel Delivery Model in der Schweine

To date, many pharmacological agents used to treat or prevent arrhythmias in open-heart cases create undesired systemic side effects. For example, ...

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

The response of single cells to anti-cancer drugs contributes significantly in determining the population response, and therefore is a major contributing factor in the overall outcome. Immunoblotting, flow cytometry and fixed cell experiments are often used to study how cells respond to anti-cancer drugs. These methods are important, but they have several shortcomings. Variability in drug responses between cancer and normal cells, and between cells of different cancer origin, and transient and rare responses are difficult to understand using population averaging assays and without being able to directly track and analyze them longitudinally. The microscope is particularly well suited to image live cells. Advancements in technology enable us to routinely image cells at a resolution that enables not only cell tracking, but also the observation of a variety of cellular responses. We describe an approach in detail that allows for the continuous time-lapse imaging of cells during the drug response for essentially as long as desired, typically up to 96 hr. Using variations of the approach, cells can be monitored for weeks. With the employment of genetically encoded fluorescent biosensors numerous processes, pathways and responses can be followed. We show examples that include tracking and quantification of cell growth and cell cycle progression, chromosome dynamics, DNA damage, and cell death. We also discuss variations of the technique and its flexibility, and highlight some common pitfalls.

Here, we describe a method of long-term time-lapse microscopy to longitudinally track single cells in response to anti-cancer therapeutics.

Durch den Spiegel: Zeitraffer-Mikroskopie und Longitudinal-Tracking von Einzelzellen Anti-Krebs-Therapeutika zu studieren

The response of single cells to anti-cancer drugs contributes significantly in determining the population response, and therefore is a major contributing ...

A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging

Age-related diseases are becoming increasingly prevalent and the burden continues to grow as our population ages. Effective treatments are necessary to lessen the impact of debilitating conditions but remain elusive in many cases. Only by understanding the causes and pathology of diseases associated with aging, can scientists begin to identify potential therapeutic targets and develop strategies for intervention. The most common age-related conditions are neurodegenerative disorders such as Parkinson's disease and blindness. Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Genome wide association studies have previously identified loci that are associated with increased susceptibility to this disease and identified two regions of interest: complement factor H (CFH) and the 10q26 locus, where the age-related maculopathy susceptibility 2 (ARMS2) and high-temperature requirement factor A1 (HtrA1) genes are located. CFH acts as a negative regulator of the alternative pathway (AP) of the complement system while HtrA1 is an extracellular serine protease. ARMS2 is located upstream of HtrA1 in the primate genome, although the gene is absent in mice. To study the effects of these genes, humanized knock-in mouse lines of Cfh and ARMS2, knockouts of Cfh, HtrA1, HtrA2, HtrA3 and HtrA4 as well as a conditional neural deletion of HtrA2 were generated. Of all the genetically engineered mice produced only mice lacking HtrA2, either systemically or in neural tissues, displayed clear phenotypes. In order to examine these mice thoroughly and systematically, an initial phenotyping schedule was established, consisting of a series of tests related to two main diseases of interest: AMD and Parkinson's. Genetically modified mice can be subjected to appropriate experiments to identify phenotypes that may be related to the associated diseases in humans. A phenotyping regimen with a mitochondrial focus is presented here alongside representative results from the tests of interest.

A reverse-genetics approach to understanding gene families associated with human disease is presented, using mouse as a model system, and the subsequent mouse phenotyping schedule is described. Because mice defective in a gene of interest, HtrA2, manifested Parkinsonian symptoms, the phenotyping regimen is focused on identifying neurological defects.

Eine Phänotypisierung Regimen für genetisch modifizierte Mäuse verwendet, um Gene in menschlichen Krankheiten des Alterns Beteiligt Study

Age-related diseases are becoming increasingly prevalent and the burden continues to grow as our population ages. Effective treatments are necessary to ...

Ultrasound-based Pulse Wave Velocity Evaluation in Mice

Arterial stiffness can be evaluated by calculating pulse wave velocity (PWV), i.e., the speed with which the pulse wave travels in a conduit vessel. This parameter is being increasingly investigated in small rodent models in which it is used for assessing alterations in vascular function related to particular genotypes/treatments or for characterizing cardiovascular disease progression. This protocol describes an image processing algorithm which leads to non-invasive arterial PWV measurement in mice using ultrasound (US) images only. The proposed technique has been used to assess abdominal aorta PWV in mice and evaluate its age-associated changes.
Abdominal aorta US scans are obtained from mice under gaseous anesthesia using a specific US device equipped with high-frequency US probes. B-mode and Pulse-Wave Doppler (PW-Doppler) images are analyzed in order to obtain diameter and mean velocity instantaneous values, respectively. For this purpose, edge detection and contour tracking techniques are employed. The single-beat mean diameter and velocity waveforms are time aligned and combined in order to achieve the diameter-velocity (lnD-V) loop. PWV values are obtained from the slope of the linear part of the loop, which corresponds to the early systolic phase.
With the present approach, anatomical and functional information about the mouse abdominal aorta can be non-invasively achieved. Requiring the processing of US images only, it may represent a useful tool for the non-invasive characterization of different arterial sites in the mouse in terms of elastic properties. The application of the present technique can be easily extended to other vascular districts, such as the carotid artery, thus providing the possibility to obtain a multi-site arterial stiffness assessment.

Arterial stiffness represents a key factor in cardiovascular disease and pulse wave velocity (PWV) can be considered as a surrogate index for arterial stiffness. This protocol describes an image processing algorithm for calculating PWV in mice based on ultrasound image processing that is applicable at different arterial sites.

Ultraschall-basierte Pulswellengeschwindigkeit Auswertung bei Mäusen

Arterial stiffness can be evaluated by calculating pulse wave velocity (PWV), i.e., the speed with which the pulse wave travels in a conduit vessel. This ...

The Rodent Model of Nonarteritic Anterior Ischemic Optic Neuropathy (rNAION)

Nonarteritic anterior ischemic optic neuropathy (NAION) is a focal ischemic lesion of the optic nerve that affects 1/700 individuals throughout their lifetime. NAION results in optic nerve edema, selective loss of the retinal ganglion cell neurons (RGCs) and atrophy of the optic nerve. A rodent model of NAION that expresses most NAION features and sequelae has been developed, which is applicable to both rats and mice. This model utilizes a focal laser application of 532 nm wavelength to illuminate a photoactive dye, Rose Bengal (RB), to cause capillary damage and leakage at the targeted anterior optic nerve (the laminar region). After rNAION induction, there is an early optic nerve ischemia, optic nerve edema, and intraneural inflammation, followed by selective RGC and axonal loss. Since the optic nerve is a CNS white matter tract, the rNAION model is applicable to mechanistic studies of selective white matter ischemia, as well as neuroprotective analyses and short and long-term mechanisms of glial and neuronal response to ischemia.

The Rodent Model of Nonarteritic Anterior Ischemic Optic Neuropathy rNAION

The following report describes how to replicate the rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION), using the appropriate dye, contact lens and laser parameters. We also reveal the appropriate steps for evaluating the rNAION lesion in vivo.

Das Nagetier-Modell der nonarteritic anteriore ischämische Optikusneuropathie (rNAION)

Nonarteritic anterior ischemic optic neuropathy (NAION) is a focal ischemic lesion of the optic nerve that affects 1/700 individuals throughout their ...

Longitudinal In Vivo Imaging of the Cerebrovasculature: Relevance to CNS Diseases

Remodeling of the brain vasculature is a common trait of brain pathologies. In vivo imaging techniques are fundamental to detect cerebrovascular plasticity or damage occurring overtime and in relation to neuronal activity or blood flow. In vivo two-photon microscopy allows the study of the structural and functional plasticity of large cellular units in the living brain. In particular, the thinned-skull window preparation allows the visualization of cortical regions of interest (ROI) without inducing significant brain inflammation. Repetitive imaging sessions of cortical ROI are feasible, providing the characterization of disease hallmarks over time during the progression of numerous CNS diseases. This technique accessing the pial structures within 250 &#956;m of the brain relies on the detection of fluorescent probes encoded by genetic cellular markers and/or vital dyes. The latter (e.g., fluorescent dextrans) are used to map the luminal compartment of cerebrovascular structures. Germane to the protocol described herein is the use of an in vivo marker of amyloid deposits, Methoxy-O4, to assess Alzheimer&#39;s disease (AD) progression. We also describe the post-acquisition image processing used to track vascular changes and amyloid depositions. While focusing presently on a model of AD, the described protocol is relevant to other CNS disorders where pathological cerebrovascular changes occur.

Longitudinal In Vivo Imaging of the Cerebrovasculature: Relevance to CNS Diseases

This manuscript describes a procedure to track the remodeling of the cerebrovasculature during amyloid plaque accumulation in vivo using longitudinal two-photon microscopy. A thinned-skull preparation enables the visualization of fluorescent dyes to assess the progression of cerebrovascular damage in a mouse model of Alzheimer&#39;s disease.

in Längsrichtung<em&gt; In Vivo</em&gt; Imaging des Cerebrovasculature: Bedeutung für ZNS-Erkrankungen

Remodeling of the brain vasculature is a common trait of brain pathologies. In vivo imaging techniques are fundamental to detect cerebrovascular ...

Development of a Direct Pulp-capping Model for the Evaluation of Pulpal Wound Healing and Reparative Dentin Formation in Mice

Dental pulp is a vital organ of a tooth fully protected by enamel and dentin. When the pulp is exposed due to cariogenic or iatrogenic injuries, it is often capped with biocompatible materials in order to expedite pulpal wound healing. The ultimate goal is to regenerate reparative dentin, a physical barrier that functions as a "biological seal" and protects the underlying pulp tissue. Although this direct pulp-capping procedure has long been used in dentistry, the underlying molecular mechanism of pulpal wound healing and reparative dentin formation is still poorly understood. To induce reparative dentin, pulp capping has been performed experimentally in large animals, but less so in mice, presumably due to their small sizes and the ensuing technical difficulties. Here, we present a detailed, step-by-step method of performing a pulp-capping procedure in mice, including the preparation of a Class-I-like cavity, the placement of pulp-capping materials, and the restoration procedure using dental composite. Our pulp-capping mouse model will be instrumental in investigating the fundamental molecular mechanisms of pulpal wound healing in the context of reparative dentin in vivo by enabling the use of transgenic or knockout mice that are widely available in the research community.

We describe a step-by-step method of performing direct pulp capping on mice teeth for the evaluation of pulpal wound healing and reparative dentin formation in vivo.

Entwicklung eines Direkt Pulp-Kappungsmodell für die Beurteilung von Pulpal Wundheilung und Reparative Dentinbildung bei Mäusen

Dental pulp is a vital organ of a tooth fully protected by enamel and dentin. When the pulp is exposed due to cariogenic or iatrogenic injuries, it is ...

Using Retinal Imaging to Study Dementia

The retina offers a unique &#8220;window&#8221; to study pathophysiological processes of dementia in the brain, as it is an extension of the central nervous system (CNS) and shares prominent similarities with the brain in terms of embryological origin, anatomical features and physiological properties.&#160; The vascular and neuronal structure in the retina can now be visualized easily and non-invasively using retinal imaging techniques, including fundus photography and optical coherence tomography (OCT), and quantified semi-automatically using computer-assisted analysis programs. Studying the associations between vascular and neuronal changes in the retina and dementia could improve our understanding of dementia and, potentially, aid in diagnosis and risk assessment.&#160; This protocol aims to describe a method of quantifying and analyzing retinal vasculature and neuronal structure, which are potentially associated with dementia. This protocol also provides examples of retinal changes in subjects with dementia, and discusses technical issues and current limitations of retinal imaging.

The retina shares prominent similarities with the brain and thus represents a unique window to study vasculature and neuronal structure in the brain non-invasively. This protocol describes a method to study dementia using retinal imaging techniques. This method can potentially aid in diagnosis and risk assessment of dementia.

Retinale Bildgebung bei der Demenz zu studieren

The retina offers a unique &#8220;window&#8221; to study pathophysiological processes of dementia in the brain, as it is an extension of the central ...