Diese Arbeit wurde durch Mittel aus dem Indiana Spinal Cord &amp; Brain Injury Research Grants (SCBI 200-12) unterstützt wird, die Ralph W. and Grace M. Showalter-Forschungspreis, der Indiana University Biological Research Grant, NIH Zuschüsse RR025761 und 1R21NS072631-01A.

Tierpflege Männlich C57 BL / 6 Mäuse wurden in Gruppen untergebracht und in 12/12 Stunden Licht / Dunkel-Zyklus gehalten mit frei, um Nahrung und Wasser ad libitum zugreifen. Die in diesem Protokoll verwendeten Tiere waren 10-12 Wochen alt. Alle Verfahren wurden unter Protokolle, die von Animal Care und Verwenden Ausschuss genehmigt Indiana University durchgeführt. 1. Chirurgische Vorbereitung <ol><li> Betäuben die Maus mit einer Ketamin / Xylazin-Mischung (87,7 mg / ml Ketamin und 12,3 mg / ml Xylazin) und Verwalten (1 ml / kg) über die IP-Injektion. </li><li> Rasieren Sie den Kopf der Maus zwischen den Ohren. </li><li> Anwenden eines Erdölbasis Gelee zu den Augen der Maus Austrocknen während der Operation zu verhindern. </li><li> Reinigen Sie den rasierten Bereich mit 10% Jod. Dann nutzen Sie 70% Ethanol zu reinigen Sie die Jod. </li><li> Befestigen Sie die Maus den Kopf in den stereotaktischen Rahmen mit den Ohr Bars und Bissplatte. Stellen Sie sicher, das Gehirn ist stabil. </li></ol> 2. Craniectomy </p&gt; <ol><li> Machen Sie einen Längsschnitt in der Mitte des Kopfes mit einer Schere. Verwenden Sie eine Gefäßklemme an der Haut weg auf die linke Seite zu halten. </li><li> Verwenden Sie ein Wattestäbchen, um die Blut-und Gewebe auf dem Knochen, den Schädel freizulegen. Lassen ausgesetzt Schädel 1 min trocknen. </li><li> Verwenden einer Pinzette, um Druck auszuüben und sicherzustellen, dass der Schädel unbeweglich bleibt. Identifizieren anatomischen Landmarken Lambda (kaudal) und Bregma (Frontalansicht). Zeichnen Sie einen Kreis in der Mitte des Lambda und Bregma mit einem Durchmesser von 4 mm und 0,5 mm von der Mittellinie. </li><li> Mit einem Bohrer, um entlang der markierten Kreis geschnitten. Blasen Sie sanft Knochenstaub entfernt. Bohren Sie nicht vollständig durch den Knochen schädigen die Dura mater zu verhindern. </li><li> Verwenden einer Pinzette, um Knochen zu entfernen und setzen die Dura mater. </li></ol> 3. Impaktion Die Auswirkungen System umfasst ein Steuerfeld, um Auswirkungen Parameter eingestellt, ein Stellglied, um den Aufprall durchzuführen, und einen stereotaktischen Rahmen, um den Akt zu sichernuator und Mauskopf für Auswirkungen. <ol><li> Voreingestellte die Geschwindigkeit des Antriebs bis 3 m / sec vor der Operation. </li><li> Voreingestellte unterschiedlichen Verformungstiefe, verschiedene Schweregrade Verletzungen verursachen. Deformationstiefen von 0,0-0,2 mm, 0,5-1,0 mm und 1,2-2,0 mm würde, mild, moderat und schwerem SHT führen sind. Dieses Protokoll erläutert, wie man einen mäßig schwerer Hirnverletzung mit einer Verformungstiefe von 1 mm unter Verwendung einer Geschwindigkeit von 3 m / sec zu erreichen. </li><li> Befestigen Sie den Antrieb an den Halter in der stereotaktischen Rahmen und mit den Mikromanipulatoren Verschieben in die runde, flache Spitze des Aktors (Durchmesser 3 mm) in der Mitte der offenen Schädelbereich zu sichern. Dann passen Sie die Spitze in einem Winkel parallel zur Oberfläche des Aufprallstelle. </li><li> Stellen Sie den Nullpunkt, indem Sie den Antrieb in der Verlängerung Modell, bis die Spitze die Oberfläche der Einschlagstelle berührt. Dann stellen Sie den Z-Kanal auf dem stereotaktischen Bedienfeld auf Null. </li><li> Fahren Sie die Schlagspitzewährend gleichzeitig bewegt den Antrieb ab 1 mm. </li><li> Drücken Sie die Taste, um die Auswirkungen Verletzungsstelle zu schlagen und erreichen eine Verformungstiefe von 1 mm. </li></ol> 4. Verletzungsstelle Verschluss <ol><li> Verwenden Sie Wattestäbchen, um das Blut nach dem Aufprall zu entfernen, aber die Verletzung Bereich nicht berühren. </li><li> Legen Sie die Maus auf einer warmen Unterlage, um die Körpertemperatur aufrecht zu erhalten. </li><li> Sobald Blutung aufgehört hat, zu nähen die Wunde geschlossen ist. Setzen Sie das Tier zurück in den Käfig sauber und lassen Sie es von der Operation über Nacht auf dem warmen Unterlage zu erholen. </li><li> Verwalten Buprenorphin 0,05-0,10 mg / kg jeden SQ 8-12 h für 2 Tage nach der Operation. </li></ol>

<ol>
	<li>Menon, D. K., Schwab, 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=Position+statement:+definition+of+traumatic+brain+injury.">Position statement: definition of traumatic brain injury.</a> Arch Phys Med Rehabil. 91 (11), 1637-1640 (2010).</li><li>Lighthall, J. W., Dixon, C. E., 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=Experimental+models+of+brain+injury.">Experimental models of brain injury.</a> J Neurotrauma. 6 (2), 83-97 (1989).</li><li>Dixon, C. E., Clfton, G. 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E., Ahmed, F., 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=Gene+expression+profile+changes+are+commonly+modulated+across+models+and+species+after+traumatic+brain+injury.">Gene expression profile changes are commonly modulated across models and species after traumatic brain injury.</a> J Neurotrauma. 20 (10), 907-927 (2003).</li><li>Anderson, R. W., Brown, C. 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=Impact+mechanics+and+axonal+injury+in+a+sheep+model.">Impact mechanics and axonal injury in a sheep model.</a> J Neurotrauma. 20 (10), 961-974 (2003).</li><li>Lighthall, J. 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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=Neutrophil+accumulation+after+traumatic+brain+injury+in+rats:+comparison+of+weight+drop+and+controlled+cortical+impact+models.">Neutrophil accumulation after traumatic brain injury in rats: comparison of weight drop and controlled cortical impact models.</a> J Neurotrauma. 11 (5), 499-506 (1994).</li><li>Werner, C., Engelhard, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pathophysiology+of+traumatic+brain+injury.">Pathophysiology of traumatic brain injury.</a> Br J Anaesth. 99 (1), 4-9 (2007).</li><li>Colicos, M. A., Dixon, C. 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The authors have nothing to disclose.

Die wichtigsten Schritte für die erfolgreiche Erzeugung konsequente TBIs mit einem elektronischen Magnet Auswirkungen System, um eine CCI verursachen, sind: 1) stabil Fixierung der Maus den Kopf in den stereotaktischen Rahmen; 2) Erzeugen der gleichen Größe des Knochenfensters zwischen Mäusen und Entfernen der Knochen, ohne die Dura unter ihm während craniectomy; 3) die korrekte Positionierung der Schlagspitze in der Mitte der Freifläche und die Gründung der Nullpunkt, bevor er auf. E...

Schädel-Hirn-Trauma (SHT) wird als eine Veränderung in der Gehirnfunktion, oder andere Anzeichen von Gehirnpathologie, durch eine äußere Kraft 1 verursacht wird. TBIs bleiben ein ernsthaftes Gesundheitsproblem in der ganzen Welt, insbesondere in den Vereinigten Staaten. Nach Angaben der Centers for Disease Control and Prevention, werden mindestens 1,7 Millionen TBIs jährlich in den Vereinigten Staaten, was zu 30,5% aller Verletzungen im Zusammenhang mit Todesfällen. Im Jahr 2000 werden die direkten medizinischen Kosten und indirekten Kosten betrugen TBIs einen geschätzten $ 76500000000 in den Vereinigten Staaten allein. Obwohl technologische und therapeutische Fortschritte in der vergangenen Jahrzehnte haben die Qualität und Länge des Lebens für die Leiden von TBIs verbessert, keine wirksame pharmazeutische oder vorbeugende Behandlungen derzeit existieren. Aufgrund der Komplexität und weitreichenden Auswirkungen der TBIs, einschließlich Gewebeläsionen, Zelltod und Axon-Degeneration sind keine zwei identischen Verletzungen; dann keinen Strom TBI Modell für Tiere reproduziertalle Aspekte der TBI in den Menschen gesehen. Allerdings Tiermodellen nicht bieten die Möglichkeit, nahezu identische Verletzungen notwendig, verschiedene Effekte der TBI mit der Hoffnung auf weitere Verständnis der klinischen Manifestationen der TBIs untersuchen zu produzieren. Die kontrollierte kortikale Auswirkungen (CCI)-Modell verwendet einen Einfluss auf physikalische System Auswirkungen auf die freigelegte Dura eines Tieres liefern. Es induziert TBIs reicht von leichten bis schweren ähnlich denen von Menschen erlebt. Diese Verletzung wurde im Frettchen 2 gekennzeichnet und später zur Verwendung bei der Ratte 3,4, Maus 5-7 und Schafen 8 angepasst. Da die erste Charakterisierung der Verletzungsstelle wurde sowohl über der Mittellinie und 2,9 lateralen Kortex 10 angeordnet. CCI bietet eine einfache und genaue Methode zur Untersuchung der Wirkungen und mögliche Behandlungen für TBIs. Neben der CCI-Modell, der Flüssigkeit Percussion und Gewichtsabfall Modelle sind Commonly zur TBIs zu produzieren. Allerdings sind diese Modelle vorhanden Einschränkungen, einschließlich weniger Kontrolle über Schädigungsparameter, Herstellung histopathalogical Änderungen nicht in der menschlichen TBIs gesehen, und größere Häufigkeit von Unfalltod in Mäusen 3,5,10. Die Druckwelle Modell wird auch verwendet, um TBIs zu produzieren. Obwohl die Druckwelle Modell nicht die histopathalogical Veränderungen erlebt reproduzieren nach einer mechanischen Aufprall, wird dieses Modell genau produzieren TBIs insbesondere von Militärpersonal 11 erlebt. Die kontrollierte kortikale Wirkungsmodell ist einfach, durch die präzise Kontrolle über Verformungsparameter wie Zeit, Geschwindigkeit und Tiefenwirkung 5 zu steuern. Solche Genauigkeit macht fast identisch replizieren Verletzungen über eine ganze Gruppe von Tieren mehr durchführbar ist. Am wichtigsten ist, CCI reproduziert TBIs mit Funktionen im menschlichen TBIs 12 zu sehen. Allerdings gibt es keine einzige Tiermodell, das bei der Wiedergabe das komplette Spektrum der pathologischen chan ganz erfolgreich istges nach SHT beobachtet. Weitere Forschung ist notwendig, um die akuten und chronischen Veränderungen, die nach SHT auftreten vollständig offenbaren. Zwei Arten von Verletzungen auftreten, nach einer TBI: primäre und sekundäre Verletzungen. Die primäre Verletzung tritt im Moment des Aufpralls und nicht empfindlich auf therapeutische Behandlungen; jedoch die sekundäre Verletzungen, die nach der ursprünglichen Verletzung bestehen unterliegen Behandlungen 13. Die kontrollierte kortikale Wirkungsmodell erzeugt die Primärverletzung, so dass die Forscher die Auswirkungen der TBI und potenzielle therapeutische Behandlungen für die potentiell langfristige Auswirkungen von Sekundärschäden zu untersuchen. Potenziale der Forschung mit dem CCI-Modell gehören neuronalen Tod, Hirnödem, Neurogenese, vaskuläre Effekte, histopathalogical Änderungen und Gedächtnisdefizite und mehr 3,13-16.

<table border="0" cellpadding="0" cellspacing="0" width="873">
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			<td height="25" style="height:25px;width:247px;">Povidone-iodine 7.5%</td>
			<td style="width:171px;">Purdue product L.P.</td>
			<td style="width:119px;"></td>
			<td style="width:336px;">Surgical scrub</td>
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		<tr height="26">
			<td height="26" style="height:26px;width:247px;">Cotton tipped applicators</td>
			<td style="width:171px;">Henry Schein</td>
			<td style="width:119px;">100-6015</td>
			<td>Remove blood and debris</td>
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		<tr height="26">
			<td height="26" style="height:26px;width:247px;">scissor</td>
			<td style="width:171px;">Fine Science Tools</td>
			<td style="width:119px;">14084-08</td>
			<td>Surgery</td>
		</tr>
		<tr height="27">
			<td height="27" style="height:27px;width:247px;">forcept</td>
			<td style="width:171px;">Fine Science Tools</td>
			<td style="width:119px;">11293-00</td>
			<td>Surgery</td>
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		<tr height="24">
			<td height="24" style="height:24px;width:247px;">hemostat</td>
			<td style="width:171px;">Fine Science Tools</td>
			<td style="width:119px;">13021-12</td>
			<td>Surgery</td>
		</tr>
		<tr height="27">
			<td height="27" style="height:27px;width:247px;">Rechargeable Cordless Micro Drill</td>
			<td style="width:171px;">Stoelting</td>
			<td style="width:119px;">58610</td>
			<td>Combine with Burrs for generating the bone window</td>
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		<tr height="25">
			<td height="25" style="height:25px;width:247px;">Burrs for Micro Drill</td>
			<td style="width:171px;">Fine Science Tools</td>
			<td style="width:119px;">19007-05</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:247px;">Suture monofilament</td>
			<td style="width:171px;">Ethicon</td>
			<td style="width:119px;">G697</td>
			<td>Suture</td>
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		<tr height="21">
			<td height="21" style="height:21px;width:247px;">tert-Amyl alcohol</td>
			<td style="width:171px;">Sigma</td>
			<td style="width:119px;">152463-250ML</td>
			<td>Making 2.5% Avertin</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:247px;">2,2,2-Tribromoethanol</td>
			<td style="width:171px;">Sigma</td>
			<td style="width:119px;">T48402-25G</td>
			<td>Making 2.5% Avertin</td>
		</tr>
	</tbody>
</table>

controlled cortical impact model for traumatic brain injury

Every year over a million Americans suffer a traumatic brain injury (TBI). Combined with the incidence of TBIs worldwide, the physical, emotional, social, and economical effects are staggering. Therefore, further research into the effects of TBI and effective treatments is necessary. The controlled cortical impact (CCI) model induces traumatic brain injuries ranging from mild to severe. This method uses a rigid impactor to deliver mechanical energy to an intact dura exposed following a craniectomy. Impact is made under precise parameters at a set velocity to achieve a pre-determined deformation depth. Although other TBI models, such as weight drop and fluid percussion, exist, CCI is more accurate, easier to control, and most importantly, produces traumatic brain injuries similar to those seen in humans. However, no TBI model is currently able to reproduce pathological changes identical to those seen in human patients. The CCI model allows investigation into the short-term and long-term effects of TBI, such as neuronal death, memory deficits, and cerebral edema, as well as potential therapeutic treatments for TBI.

Die kontrollierte kortikale Wirkungsmodell produziert TBIs reichen im Schweregrad von leicht bis schwer. Post-Einfluss die Höhe der Schädel Schwellungen, Blutungen und Hirn Verzerrung an der Einschlagstelle wird die Schwere der Verletzungen von der Geschwindigkeits-und Verformungstiefe Parameter resultieren, zu offenbaren. Mild TBIs führen Schädel Schwellung an der Einschlagstelle und leichte Blutungen aufgrund der begrenzten Dauer Verletzung. Eine moderate TBI zeigt Hirnschwellung und erhöhte Blutungs wegen Verlet...

Watch this Scientific Journal Video about Controlled Cortical Impact Model for Traumatic Brain Injury at JoVE.com

Controlled Cortical Impact Model for Traumatic Brain Injury

Traumatic brain injuries (TBIs) remain a serious health problem. Using the controlled cortical impact surgery model, research on the effects of TBI and possible treatment methods may be performed.

Controlled Cortical Impact-Modell für traumatische Hirnverletzung

Every year over a million Americans suffer a traumatic brain injury (TBI).  Combined with the incidence of TBIs worldwide, the physical, emotional, ...

controlled-cortical-impact-model-for-traumatic-brain-injury

Research

JoVE Journal

Medicine

28.4K Aufrufe.  Indiana University School of Medicine. Traumatic brain injuries (TBIs) remain a serious health problem. Using the controlled cortical impact surgery model, research on the effects of TBI and possible treatment methods may be performed.

Serie: Controlled Cortical Impact Model for Traumatic Brain Injury

Pressure Controlled Ventilation to Induce Acute Lung Injury in Mice

Murine models are extensively used to investigate acute injuries of different organs systems (1-34). Acute lung injury (ALI), which occurs with prolonged mechanical ventilation, contributes to morbidity and mortality of critical illness, and studies on novel genetic or pharmacological targets are areas of intense investigation (1-3, 5, 8, 26, 30, 33-36). ALI is defined by the acute onset of the disease, which leads to non-cardiac pulmonary edema and subsequent impairment of pulmonary gas exchange (36). We have developed a murine model of ALI by using a pressure-controlled ventilation to induce ventilator-induced lung injury (2). For this purpose, C57BL/6 mice are anesthetized and a tracheotomy is performed followed by induction of ALI via mechanical ventilation. Mice are ventilated in a pressure-controlled setting with an inspiratory peak pressure of 45 mbar over 1 - 3 hours. As outcome parameters, pulmonary edema (wet-to-dry ratio), bronchoalveolar fluid albumin content, bronchoalveolar fluid and pulmonary tissue myeloperoxidase content and pulmonary gas exchange are assessed (2). Using this technique we could show that it sufficiently induces acute lung inflammation and can distinguish between different treatment groups or genotypes (1-3, 5). Therefore this technique may be helpful for researchers who pursue molecular mechanisms involved in ALI using a genetic approach in mice with gene-targeted deletion.

A murine model for ventilator induced lung injury is an important tool to study an acute lung injury in vivo. Here, we report an easy applicable in situ model for acute lung injury using high-pressure mechanical ventilation to induce acute failure of the lung.

Pressure Controlled Ventilation zu Acute Lung Injury in Mäusen zu induzieren

Murine models are extensively used to investigate acute injuries of different organs systems (1-34). Acute lung injury (ALI), which occurs with prolonged ...

Forschung

Medizin

Controlled Cervical Laceration Injury in Mice

Use of genetically modified mice enhances our understanding of molecular mechanisms underlying several neurological disorders such as a spinal cord injury (SCI). Freehand manual control used to produce a laceration model of SCI creates inconsistent injuries often associated with a crush or contusion component and, therefore, a novel technique was developed. Our model of cervical laceration SCI has resolved inherent difficulties with the freehand method by incorporating 1) cervical vertebral stabilization by vertebral facet fixation, 2) enhanced spinal cord exposure, and 3) creation of a reproducible laceration of the spinal cord using an oscillating blade with an accuracy of &plusmn;0.01 mm in depth without associated contusion. Compared to the standard methods of creating a SCI laceration such as freehand use of a scalpel or scissors, our method has produced a consistent lesion. This method is useful for studies on axonal regeneration of corticospinal, rubrospinal, and dorsal ascending tracts.

A novel technique to create a reproducible in vivo model of cervical spinal cord laceration injury in the mouse is described. This technique is based on spine stabilization by fixation of the cervical facets and laceration of the spinal cord using an oscillating blade with an accuracy of &plusmn;0.01 mm.

Controlled Cervical Laceration Verletzungen in Mäuse

Use of genetically modified mice enhances our  understanding of molecular mechanisms underlying several neurological disorders  such as a spinal cord ...

Stretch in Brain Microvascular Endothelial Cells (cEND) as an In Vitro Traumatic Brain Injury Model of the Blood Brain Barrier

Due to the high mortality incident brought about by traumatic brain injury (TBI), methods that would enable one to better understand the underlying mechanisms involved in it are useful for treatment. There are both in vivo and in vitro methods available for this purpose. In vivo models can mimic actual head injury as it occurs during TBI. However, in vivo techniques may not be exploited for studies at the cell physiology level. Hence, in vitro methods are more advantageous for this purpose since they provide easier access to the cells and the extracellular environment for manipulation.
Our protocol presents an in vitro model of TBI using stretch injury in brain microvascular endothelial cells. It utilizes pressure applied to the cells cultured in flexible-bottomed wells. The pressure applied may easily be controlled and can produce injury that ranges from low to severe. The murine brain microvascular endothelial cells (cEND) generated in our laboratory is a well-suited model for the blood brain barrier (BBB) thus providing an advantage to other systems that employ a similar technique. In addition, due to the simplicity of the method, experimental set-ups are easily duplicated. Thus, this model can be used in studying the cellular and molecular mechanisms involved in TBI at the BBB.

Stretch in Brain Microvascular Endothelial Cells cEND as an In Vitro Traumatic Brain Injury Model of the Blood Brain Barrier

In vitro traumatic brain injury models are being developed to reproduce in vivo brain deformation. Stretch-induced injury has been employed for astrocytes, neurons, glial cells, aortic, and brain endothelial cells. However, our system uses a blood brain barrier (BBB) model that possesses properties constituting a legitimate model of the BBB to establish an in vitro&#160;TBI model.

Stretchlimousine in Gehirn mikrovaskulären Endothelzellen (CEND) als<em&gt; In Vitro</em&gt; Traumatische Hirnverletzung Modell der Blut-Hirn-Schranke

Due to the high mortality incident brought about by traumatic brain injury (TBI), methods that would enable one to better understand the underlying ...

Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration

Renal ischaemia reperfusion injury (IRI) is a common cause of acute kidney injury (AKI) in patients and occlusion of renal blood flow is unavoidable during renal transplantation. Experimental models that accurately and reproducibly recapitulate renal IRI are crucial in dissecting the pathophysiology of AKI and the development of novel therapeutic agents. Presented here is a mouse model of renal IRI that results in reproducible AKI. This is achieved by a midline laparotomy approach for the surgery with one incision allowing both a right nephrectomy that provides control tissue and clamping of the left renal pedicle to induce ischaemia of the left kidney. By careful monitoring of the clamp position and body temperature during the period of ischaemia this model achieves reproducible functional and structural injury. Mice sacrificed 24 hr&#160;following surgery demonstrate loss of renal function with elevation of the serum or plasma creatinine level as well as structural kidney damage with acute tubular necrosis evident. Renal function improves and the acute tissue injury resolves during the course of 7 days following renal IRI such that this model may be used to study renal regeneration. This model of renal IRI has been utilized to study the molecular and cellular pathophysiology of AKI as well as analysis of the subsequent renal regeneration.

The mouse model of renal ischaemia reperfusion injury described here comprises of a right nephrectomy that provides control tissue and clamping of the left renal pedicle to induce ischaemia that results in acute kidney injury. This model uses a midline laparotomy approach with all steps performed via one incision.

Renale Ischämie Reperfusionsschaden: Ein Maus-Modell der Schädigung und Regeneration

Renal ischaemia reperfusion injury (IRI) is a common cause of acute kidney injury (AKI) in patients and occlusion of renal blood flow is unavoidable ...

A Novel Model of Mild Traumatic Brain Injury for Juvenile Rats

Despite growing evidence that childhood represents a major risk period for mild traumatic brain injury (mTBI) from sports-related concussions, motor vehicle accidents, and falls, a reliable animal model of mTBI had previously not been developed for this important aspect of development. The modified weight-drop technique employs a glancing impact to the head of a freely moving rodent transmitting acceleration, deceleration, and rotational forces upon the brain. When applied to juvenile rats, this modified weight-drop technique induced clinically relevant behavioural outcomes that were representative of post-concussion symptomology. The technique is a rapidly applied procedure with an extremely low mortality rate, rendering it ideal for high-throughput studies of therapeutics. In addition, because the procedure involves a mild injury to a closed head, it can easily be used for studies of repetitive brain injury. Owing to the simplistic nature of this technique, and the clinically relevant biomechanics of the injury pathophysiology, the modified weight-drop technique provides researchers with a reliable model of mTBI that can be used in a wide variety of behavioural, molecular, and genetic studies.

The modified weight-drop technique is an easy, cost-effective procedure used for the induction of mild traumatic brain injury in juvenile rats. This novel technique produces clinically relevant symptomology that will advance the study of mild traumatic brain injury (mTBI) and concussion.

Roman Modell Mild traumatische Hirnverletzung für jungen Ratten

Despite growing evidence that childhood represents a major risk period for mild traumatic brain injury (mTBI) from sports-related concussions, motor ...

Calibrated Forceps Model of Spinal Cord Compression Injury

Compression injuries of the murine spinal cord are valuable animal models for the study of spinal cord injury (SCI) and spinal regenerative therapy. The calibrated forceps model of compression injury is a convenient, low cost, and very reproducible animal model for SCI. We used a pair of modified forceps in accordance with the method published by Plemel et al. (2008) to laterally compress the spinal cord to a distance of 0.35 mm. In this video, we will demonstrate a dorsal laminectomy to expose the spinal cord, followed by compression of the spinal cord with the modified forceps. In the video, we will also address issues related to the care of paraplegic laboratory animals. This injury model produces mice that exhibit impairment in sensation, as well as impaired hindlimb locomotor function. Furthermore, this method of injury produces consistent aberrations in the pathology of the SCI, as determined by immunohistochemical methods. After watching this video, viewers should be able to determine the necessary supplies and methods for producing SCI of various severities in the mouse for studies on SCI and/or treatments designed to mitigate impairment after injury.

Spinal cord injury models should be highly reproducible. We demonstrate that the calibrated forceps compression model of spinal cord injury is an easy to use surgical method for generating reproducible injuries to the murine spinal cord.

Calibrated Zange Modell Spinal Cord Injury Compression

Compression injuries of the murine spinal cord are valuable animal models for the study of spinal cord injury (SCI) and spinal regenerative therapy. The ...

A Tissue Displacement-based Contusive Spinal Cord Injury Model in Mice

Producing a consistent and reproducible contusive spinal cord injury (SCI) is critical to minimizing behavioral and histological variabilities between experimental animals. Several contusive SCI models have been developed to produce injuries using different mechanisms. The severity of the SCI is based on the height that a given weight is dropped, the injury force, or the spinal cord displacement. In the current study, we introduce a novel mouse contusive SCI device, the Louisville Injury System Apparatus (LISA) impactor, which can create a displacement-based SCI with high injury velocity and accuracy. This system utilizes laser distance sensors combined with advanced software to produce graded and highly-reproducible injuries. We performed a contusive SCI at the 10th thoracic vertebral (T10) level in mice to demonstrate the step-by-step procedure. The model can also be applied to the cervical and lumbar spinal levels.

We introduce a tissue displacement-based contusive spinal cord injury model that can produce a consistent contusive spinal cord injury in adult mice.

Ein Tissue Displacement-basierte Contusive Spinal Cord Verletzung Modell in Mäusen

Producing a consistent and reproducible contusive spinal cord injury (SCI) is critical to minimizing behavioral and histological variabilities between ...

A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury

Mild Traumatic Brain Injury (mTBI) can result in the acute loss of brain function, including a period of confusion, a loss of consciousness (LOC), focal neurological deficits and even amnesia. Athletes participating in contact sports are at high risk of exposure to large number of mTBIs. In terms of the level of injury in a sporting athlete, a mTBI is defined as a mild injury that does not cause gross pathological changes, but does cause short-term neurological deficits that are spontaneously resolved. Despite previous attempts to model mTBI in mice and rats, many have reported gross adverse effects including skull fractures, intracerebral bleeding, axonal injury and neuronal cell death. Herein, we describe our highly reproducible animal model of mTBI that reproduces clinically relevant symptoms. This model uses a custom made pneumatic impactor device to deliver a closed-head trauma. This impact is made under precise velocity and deformation parameters, creating a reliable and reproducible model to examine the mechanisms that contribute to effects of single or repetitive concussive mTBI.

Athletes absorb several hundred mild traumatic brain injuries (mTBI)/concussions every year; however, the consequence of these on the brain is poorly understood. Therefore, an animal model of single and repetitive mTBI that consistently replicates clinically relevant symptoms provides the means to advance the study of mTBI and concussion.

Ein Mausmodell der einzelnen und repetitiven milden traumatischen Gehirnverletzung

Mild Traumatic Brain Injury (mTBI) can result in the acute loss of brain function, including a period of confusion, a loss of consciousness (LOC), focal ...

Semi-quantitative Assessment Using [18F]FDG Tracer in Patients with Severe Brain Injury

Patients with severe traumatic brain injury (sTBI) have difficulty knowing whether they are accurately expressing their thoughts and emotions because of disorders of consciousness, disrupted higher brain function, and verbal disturbances. As a consequence of an insufficient ability to communicate, objective evaluations are needed from family members, medical staff, and caregivers. One such evaluation is the assessment of functioning brain areas. Recently, multimodal brain imaging has been used to explore the function of damaged brain areas. [18F]-fluorodeoxyglucose positron emission tomography-computed tomography ([18F]FDG-PET/CT) is a successful tool for examining brain function. However, the assessment of brain glucose metabolism based on [18F]FDG-PET/CT is not standardized and depends on several varying parameters, as well as the patient&#39;s condition. Here, we describe a series of semiquantitative assessment protocols for a region-of-interest (ROI) image analysis using self-produced [18F]FDG tracers in patients with sTBI. The protocol focuses on screening the participants, preparing the [18F]FDG tracer in the hot lab, scheduling the acquisition of [18F]FDG-PET/CT brain images, and measuring glucose metabolism using the ROI analysis from a targeted brain area.

Semi-quantitative Assessment Using [18F]FDG Tracer in Patients with Severe Brain Injury

[18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography is useful for studying glucose metabolism related to brain function. Here, we present a protocol for an [18F]FDG tracer set-up and semiquantitative assessment of the region-of-interest analysis for targeted brain areas associated with clinical manifestations in patients with severe traumatic brain injury.

Semi-quantitative Bewertung mit [18F] FDG Tracer bei Patienten mit schweren Hirnverletzungen

Patients with severe traumatic brain injury (sTBI) have difficulty knowing whether they are accurately expressing their thoughts and emotions because of ...

Tracking Superparamagnetic Iron Oxide-labeled Mesenchymal Stem Cells using MRI after Intranasal Delivery in a Traumatic Brain Injury Murine Model

Stem cell-based therapies for brain injuries, such as traumatic brain injury (TBI), are a promising approach for clinical trials. However, technical hurdles such as invasive cell delivery and tracking with low transplantation efficiency remain challenges in translational stem-based therapy. This article describes an emerging technique for stem cell labeling and tracking based on the labeling of the mesenchymal stem cells (MSCs) with superparamagnetic iron oxide (SPIO)&#160;nanoparticles, as well as intranasal delivery of the labeled MSCs. These nanoparticles are fluorescein isothiocyanate (FITC)-embedded and safe to label the MSCs, which are subsequently delivered to the brains of TBI-induced mice by the intranasal route. They are then tracked non-invasively in vivo by real-time magnetic resonance imaging (MRI). Important advantages of this technique that combines SPIO for cell labeling and intranasal delivery include (1) non-invasive, in vivo MSC tracking after delivery for long tracking periods, (2) the possibility of multiple dosing regimens due to the non-invasive route of MSC delivery, and (3) possible applications to humans, owing to the safety of SPIO, non-invasive nature of the cell-tracking method by MRI, and route of administration.

Presented here is a protocol for non-invasive mesenchymal stem cell (MSC) delivery and tracking in a mouse model of traumatic brain injury. Superparamagnetic iron oxide&#160;nanoparticles are employed as a magnetic resonance imaging (MRI) probe for MSC labeling and non-invasive in vivo tracking following intranasal delivery using real-time MRI.

Verfolgung von superparamagnetischen Eisenoxid-beschrifteten mesenchymalen Stammzellen mit MRT nach intranasaler Lieferung in einem traumatischen Hirnverletzungs-Murine-Modell

Stem cell-based therapies for brain injuries, such as traumatic brain injury (TBI), are a promising approach for clinical trials. However, technical ...