Name: controlled cortical impact model for traumatic brain injury
Uploaded: 2014-08-05T16:00:00.000+00:00
Duration: 5 min 30 s
Description: Watch this Scientific Journal Video about Controlled Cortical Impact Model for Traumatic Brain Injury at JoVE.com

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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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=A+model+of+parasagittal+controlled+cortical+impact+in+the+mouse:+cognitive+and+histopathologic+effects.">A model of parasagittal controlled cortical impact in the mouse: cognitive and histopathologic effects.</a> J Neurotrauma. 12 (2), 169-178 (1995).</li><li>Hannay, H. J., Feldman, Z., 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=Validation+of+a+controlled+cortical+impact+model+of+head+injury+in+mice.">Validation of a controlled cortical impact model of head injury in mice.</a> J Neurotrauma. 16 (11), 1103-1114 (1999).</li><li>Natale, J. 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. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Controlled+cortical+impact:+a+new+experimental+brain+injury+model.">Controlled cortical impact: a new experimental brain injury model.</a> J Neurotrauma. 5 (1), 1-15 (1988).</li><li>Chen, S., Pickard, J. 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=Time+course+of+cellular+pathology+after+controlled+cortical+impact+injury.">Time course of cellular pathology after controlled cortical impact injury.</a> Exp Neurol. 182 (1), 87-102 (2003).</li><li>Long, J. B., Bentley, T. L., 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=Blast+overpressure+in+rats:+recreating+a+battlefield+injury+in+the+laboratory.">Blast overpressure in rats: recreating a battlefield injury in the laboratory.</a> J Neurotrauma. 26 (6), 827-840 (2009).</li><li>Clark, R. S., Schiding, J. 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. 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=Delayed,+selective+neuronal+death+following+experimental+cortical+impact+injury+in+rats:+possible+role+in+memory+deficits.">Delayed, selective neuronal death following experimental cortical impact injury in rats: possible role in memory deficits.</a> Brain Res. 739 (1-2), 111-119 (1996).</li><li>Raghavendra Rao, V. L., Dogan, 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=Traumatic+brain+injury+leads+to+increased+expression+of+peripheral-type+benzodiazepine+receptors,+neuronal+death,+and+activation+of+astrocytes+and+microglia+in+rat+thalamus.">Traumatic brain injury leads to increased expression of peripheral-type benzodiazepine receptors, neuronal death, and activation of astrocytes and microglia in rat thalamus.</a> Exp Neurol. 161 (1), 102-114 (2000).</li><li>Gao, X., Chen, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Moderate+traumatic+brain+injury+promotes+neural+precursor+proliferation+without+increasing+neurogenesis+in+the+adult+hippocampus.">Moderate traumatic brain injury promotes neural precursor proliferation without increasing neurogenesis in the adult hippocampus.</a> Exp Neurol. 239, 38-48 (2013).</li></ol>

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.

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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

Controlled Cortical Impact Model of Mouse Brain Injury with Therapeutic Transplantation of Human Induced Pluripotent Stem Cell-Derived Neural Cells

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide. Disease pathology due to TBI progresses from the primary mechanical insult to secondary injury processes, including apoptosis and inflammation. Animal modeling has been valuable in the search to unravel injury mechanisms and evaluate potential neuroprotective therapies. This protocol describes the controlled cortical impact (CCI) model of focal, open-head TBI. Specifically, parameters for producing a mild unilateral cortical injury are described. Behavioral consequences of CCI are analyzed using the adhesive tape removal test of bilateral sensorimotor integration. Regarding experimental therapy for TBI pathology, this protocol also illustrates a process for transplanting cultured cells into the brain. Neural cell cultures derived from human induced pluripotent stem cells (hiPSCs) were chosen for their potential to show superior functional restoration in human TBI patients. Chronic survival of hiPSCs in the host mouse brain tissue is detected using a modified DAB immunohistochemical process.

This protocol demonstrates methodologies for a mouse model of open-skull traumatic brain injury and transplantation of cultured human induced pluripotent stem cell-derived cells into the injury site. Behavioral and histologic tests of outcomes from these procedures are also described in brief.

Kontrolliertes kortikales Wirkungsmodell der Maushirnverletzung mit therapeutischer Transplantation von humaninduzierten Pluripotenten Stammzell-abgeleiteten Neuralzellen

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide. Disease pathology due to TBI progresses from the primary mechanical ...

Forschung

Entwicklungsbiologie

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.

Ein Repetitive erschütternder Head Injury-Modell in Mäusen

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

Medizin

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 ...

Murine Model of Controlled Cortical Impact for the Induction of Traumatic Brain Injury

The Centers for Disease Control and Injury Prevention estimate that almost 2 million people sustain a traumatic brain injury (TBI) every year in the United States. In fact, TBI is a contributing factor to over a third of all injury-related mortality. Nonetheless, the cellular and molecular mechanisms underlying the pathophysiology of TBI are poorly understood. Thus, preclinical models of TBI capable of replicating the injury mechanisms pertinent to TBI in human patients are a critical research need. The controlled cortical impact (CCI) model of TBI utilizes a mechanical device to directly impact the exposed cortex. While no model can full recapitulate the disparate injury patterns and heterogeneous nature of TBI in human patients, CCI is capable of inducing a wide range of clinically applicable TBI. Furthermore, CCI is easily standardized allowing investigators to compare results across experiments as well as across investigative groups. The following protocol is a detailed description of applying a severe CCI with a commercially available impacting device in a murine model of TBI.

Here we describe a protocol for the induction of murine traumatic brain injury via an open-head controlled cortical impact.

Murine Modell der kontrollierten kortikalen Auswirkungen für die Induktion von traumatischen Hirnverletzungen

The Centers for Disease Control and Injury Prevention estimate that almost 2 million people sustain a traumatic brain injury (TBI) every year in the ...

Neurowissenschaften

Low-intensity Blast Wave Model for Preclinical Assessment of Closed-head Mild Traumatic Brain Injury in Rodents

Traumatic brain injury (TBI) is a large-scale public health problem. Mild TBI is the most prevalent form of neurotrauma and accounts for a large number of medical visits in the United States. There are currently no FDA-approved treatments available for TBI. The increased incidence of military-related, blast-induced TBI further accentuates the urgent need for effective TBI treatments. Therefore, new preclinical TBI animal models that recapitulate aspects of human blast-related TBI will greatly advance the research efforts into the neurobiological and pathophysiological processes underlying mild to moderate TBI as well as the development of novel therapeutic strategies for TBI.
Here we present a reliable, reproducible model for the investigation of the molecular, cellular, and behavioral effects of mild to moderate blast-induced TBI. We describe a step-by-step protocol for closed-head, blast-induced mild TBI in rodents using a bench-top setup consisting of a gas-driven shock tube equipped with piezoelectric pressure sensors to ensure consistent test conditions. The benefits of the setup that we have established are its relative low-cost, ease of installation, ease of use and high-throughput capacity. Further advantages of this non-invasive TBI model include the scalability of the blast peak overpressure and the generation of controlled reproducible outcomes. The reproducibility and relevance of this TBI model has been evaluated in a number of downstream applications, including neurobiological, neuropathological, neurophysiological and behavioral analyses, supporting the use of this model for the characterization of processes underlying the etiology of mild to moderate TBI.

We present here a protocol of a blast wave model for rodents to investigate neurobiological and pathophysiological effects of mild to moderate traumatic brain injury. We established a gas-driven, bench-top setup equipped with pressure sensors allowing for reliable and reproducible generation of blast-induced mild to moderate traumatic brain injury.

Low-Intensity Blast Wave Model for Preclinical Assessment of Closed-Head Mild Traumatic Brain Injury bei Nagetieren

Traumatic brain injury (TBI) is a large-scale public health problem. Mild TBI is the most prevalent form of neurotrauma and accounts for a large number of ...

A Preclinical Controlled Cortical Impact Model for Traumatic Hemorrhage Contusion and Neuroinflammation

Cerebral contusion is a severe medical problem affecting millions of people worldwide each year. There is an urgent need to understand the pathophysiological mechanism and to develop effective therapeutic strategy for this devastating neurological disorder. Intraparenchymal hemorrhage and post-traumatic inflammatory response induced by initial physical impact can aggravate microglia/macrophage activation and neuroinflammation which subsequently worsen brain pathology. We provide here a controlled cortical impact (CCI) protocol that can reproduce experimental cortical contusion in mice by using a pneumatic impactor system to deliver mechanical force with controllable magnitude and velocity onto the dural surface. This preclinical model allows researchers to induce moderately severe focal cerebral contusion in mice and to investigate a wide range of post-traumatic pathological progressions including hemorrhage contusion, microglia/macrophage activation, iron toxicity, axonal injury, as well as short-term and long-term neurobehavioral deficits. The present protocol can be useful for exploring the long-term effects of and potential interventions for cerebral contusion.

<meta charset="utf8"></head><body>Ein präklinisches Modell für kontrollierte kortikale Auswirkungen bei traumatischen Blutungen, Prellungen und Neuroinflammation

Intraparenchymal hemorrhage and neuroinflammation accompanied by cerebral contusion can trigger severe secondary brain injury. This protocol details a mouse controlled cortical impact (CCI) model allowing researchers to study hemorrhage contusion and post-traumatic immune responses and explore potential therapeutics.

Ein präklinisches Modell für kontrollierte kortikale Auswirkungen bei traumatischen Blutungen, Prellungen und Neuroinflammation

Cerebral contusion is a severe medical problem affecting millions of people worldwide each year. There is an urgent need to understand the ...

Electromagnetic Controlled Closed-Head Model of Mild Traumatic Brain Injury in Mice

Highly reproducible animal models of traumatic brain injury (TBI), with well-defined pathologies, are needed for testing therapeutic interventions and understanding the mechanisms of how a TBI alters brain function. The availability of multiple animal models of TBI is necessary to model the different aspects and severities of TBI seen in people. This manuscript describes the use of a midline closed head injury (CHI) to develop a mouse model of mild TBI. The model is considered mild because it does not produce structural brain lesions based on neuroimaging or gross neuronal loss. However, a single impact creates enough pathology that cognitive impairment is measurable at least 1 month after injury. A step-by-step protocol to induce a CHI in mice using a stereotaxically guided electromagnetic impactor is defined in the paper. The benefits of the mild midline CHI model include the reproducibility of the injury-induced changes with low mortality. The model has been temporally characterized up to 1 year after the injury for neuroimaging, neurochemical, neuropathological, and behavioral changes. The model is complementary to open skull models of controlled cortical impact using the same impactor device. Thus, labs can model both mild diffuse TBI and focal moderate-to-severe TBI with the same impactor.

The protocol describes mild traumatic brain injury in a mouse model. In particular, a step-by-step protocol to induce a mild midline closed head injury and the characterization of the animal model is fully explained.

Elektromagnetisch gesteuertes Closed-Head-Modell für leichtes Schädel-Hirn-Trauma bei Mäusen

Highly reproducible animal models of traumatic brain injury (TBI), with well-defined pathologies, are needed for testing therapeutic interventions and ...

Assessing Changes in Synaptic Plasticity Using an Awake Closed-Head Injury Model of Mild Traumatic Brain Injury

Mild traumatic brain injuries (mTBIs) are a prevalent health issue in North America. There is increasing pressure to utilize ecologically valid models of closed-head mTBI in the preclinical setting to increase translatability to the clinical population. The awake closed-headed injury (ACHI) model uses a modified controlled cortical impactor to deliver closed-headed injury, inducing clinically relevant behavioral deficits without the need for a craniotomy or the use of an anesthetic.
This technique does not normally induce fatalities, skull fractures, or brain bleeds, and is more consistent with being a mild injury. Indeed, the mild nature of the ACHI procedure makes it ideal for studies investigating repetitive mTBI (r-mTBI). Growing evidence indicates that r-mTBI can result in a cumulative injury that produces behavioral symptoms, neuropathological changes, and neurodegeneration. r-mTBI is common in youths playing sports, and these injuries occur during a period of robust synaptic reorganization and myelination, making the younger population particularly vulnerable to the long-term influences of r-mTBI.
Further, r-mTBI occurs in cases of intimate partner violence, a condition for which there are few objective screening measures. In these experiments, synaptic function was assessed in the hippocampus in juvenile rats that had experienced r-mTBI using the ACHI model. Following the injuries, a tissue slicer was utilized to make hippocampal slices to evaluate bidirectional synaptic plasticity in the hippocampus at either 1 or 7 days following the r-mTBI. Overall, the ACHI model provides researchers with an ecologically valid model to study changes in synaptic plasticity following mTBI and r-mTBI.

Here, it is demonstrated how an awake closed-head injury model can be used for examining the effects of repeated mild traumatic brain injury (r-mTBI) on synaptic plasticity in the hippocampus. The model replicates important features of r-mTBI in patients and is used in conjunction with in vitro electrophysiology.

Beurteilung von Veränderungen in der synaptischen Plastizität unter Verwendung eines wachen geschlossenen Kopfverletzungsmodells für ein leichtes Schädel-Hirn-Trauma

Mild traumatic brain injuries (mTBIs) are a prevalent health issue in North America. There is increasing pressure to utilize ecologically valid models of ...

rmTBI-Induktion bei Mäusen über eine geschlossene Kopfverletzungsmethode

Modified Mouse Model of Repetitive Mild Traumatic Brain Injury Incorporating Thinned-Skull Window and Fluid Percussion

Mild traumatic brain injury is a clinically highly heterogeneous neurological disorder. Highly reproducible traumatic brain injury (TBI) animal models with well-defined pathologies are urgently needed for studying the mechanisms of neuropathology after mild TBI and testing therapeutics. Replicating the entire sequelae of TBI in animal models has proven to be a challenge. Therefore, the availability of multiple animal models of TBI is necessary to account for the diverse aspects and severities seen in TBI patients. CHI is one of the most common methods for fabricating rodent models of rmTBI. However, this method is susceptible to many factors, including the impact method used, the thickness and shape of the skull bone, animal apnea, and the type of head support and immobilization utilized. The aim of this protocol is to demonstrate a combination of the thinned-skull window and fluid percussion injury (FPI) methods to produce a precise mouse model of CHI-associated rmTBI. The primary objective of this protocol is to minimize factors that could impact the accuracy and consistency of CHI and FPI modeling, including skull bone thickness, shape, and head support. By utilizing a thinned-skull window method, potential inflammation due to craniotomy and FPI is minimized, resulting in an improved mouse model that replicates the clinical features observed in patients with mild TBI. Results from behavior and histological analysis using hematoxylin and eosin (HE) staining suggest that rmTBI can lead to a cumulative injury that produces changes in both behavior and gross morphology of the brain. Overall, the modified CHI-associated rmTBI presents a useful tool for researchers to explore the underlying mechanisms that contribute to focal and diffuse pathophysiological changes in rmTBI.

Autor im Rampenlicht: Optimierung von Nagetiermodellen zur Untersuchung der Mechanismen und der Rehabilitation bei wiederholten leichten traumatischen Hirnverletzungen

This protocol presents a modified mouse model of repetitive mild traumatic brain injury (rmTBI) induced via a closed-head injury (CHI) method. The approach features a thinned-skull window and fluid percussion to reduce the inflammation commonly caused by meninges exposure, along with improved reproducibility and accuracy in modeling rmTBI in rodents.

Modifiziertes Mausmodell für repetitives leichtes Schädel-Hirn-Trauma mit verdünntem Schädelfenster und flüssiger Perkussion

Mild traumatic brain injury is a clinically highly heterogeneous neurological disorder. Highly reproducible traumatic brain injury (TBI) animal models ...

Controlled Cortical Impact-Modell für traumatische Hirnverletzung

Zusammenfassung

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