Ce travail a été soutenu par un financement du cordon Indiana épinière et cerveau de subventions de recherche de blessures (200-12) SCBI, Ralph W. et Grace M. bourse de recherche Showalter, Indiana University Research Grant biologique, NIH subventions RR025761 et 1R21NS072631-01A.

Protection des animaux Homme C57 BL / 6 souris ont été logées en groupe et maintenus dans un cycle 12/12 h de lumière / obscurité avec une connexion pour accéder à la nourriture et de l&#39;eau ad libitum. Les animaux utilisés dans ce protocole étaient âgés de 10-12 semaines. Toutes les procédures ont été réalisées selon des protocoles approuvés par le Comité de soins et l&#39;utilisation des animaux de l&#39;Université d&#39;Indiana. 1. Préparation chirurgicale <ol><li> Anesthésier la souris en utilisant un mélange de kétamine / xylazine (87,7 mg / ml de kétamine et de 12,3 mg / ml de xylazine) et à administrer (1 ml / kg) par injection IP. </li><li> Raser la tête de la souris entre les oreilles. </li><li> Appliquer une gelée à base de pétrole pour les yeux de la souris afin d&#39;éviter le dessèchement pendant la chirurgie. </li><li> Nettoyer la zone rasée avec 10% de l&#39;iode. Ensuite, utilisez 70% d&#39;éthanol pour nettoyer l&#39;iode. </li><li> Fixez la tête de la souris dans le cadre stéréotaxique utilisant les barres d&#39;oreilles et la plaque de morsure. S&#39;assurer que le cerveau est stable. </li></ol> 2. Craniectomie </p&gt; <ol><li> Faire une incision longitudinale dans le milieu de la tête avec des ciseaux. Utilisez une pince hémostatique pour maintenir la peau sur le côté gauche. </li><li> Utilisez un coton-tige pour enlever le sang et les tissus de l&#39;os pour exposer le crâne. Laisser crâne exposé à sécher pendant 1 min. </li><li> Utilisez une pince pour appliquer la pression et faire en sorte que le crâne reste immobile. Identifier les repères anatomiques Lambda (caudale aspect) et Bregma (aspect le frontal). Dessiner un cercle au centre du bregma et lambda avec un diamètre de 4 mm et de 0,5 mm de la ligne médiane. </li><li> Utilisez une perceuse pour couper le long du cercle marqué. Soufflez doucement la poussière d&#39;os loin. Ne pas percer complètement à travers l&#39;os pour éviter d&#39;endommager la dure-mère. </li><li> Utilisez une pince pour retirer les os et exposer la dure-mère. </li></ol> 3. Impaction Le système d&#39;impact comprend un boîtier de commande pour définir les paramètres d&#39;impact, un actionneur pour effectuer l&#39;impaction, et un cadre stéréotaxique pour sécuriser l&#39;acteuator et chef de la souris pour l&#39;impact. <ol><li> Pré-régler la vitesse de l&#39;actionneur à 3 m / sec avant l&#39;intervention chirurgicale. </li><li> Prédéfinie différente profondeur de déformation pour induire différents niveaux de gravité des blessures. des profondeurs de déformation de 0.0-0.2 mm, 0,5-1,0 mm et 1,2-2,0 mm entraînerait TCC légers, modérés et sévères, respectivement. Ce protocole a expliqué comment parvenir à une lésion cérébrale modérément sévère avec une profondeur de 1 mm de déformation en utilisant une vitesse de 3 m / sec. </li><li> Fixez l&#39;actionneur au titulaire dans le cadre stéréotaxique et d&#39;utiliser les micro-manipulateurs déplacer pour fixer le, bout plat rond de l&#39;actionneur (de 3 mm de diamètre) dans le centre de la zone ouverte du crâne. Puis ajustez la pointe à un angle parallèle à la surface de lieu de l&#39;impact. </li><li> Établir le point zéro par déplacement vers le bas de l&#39;actionneur dans le modèle s&#39;étendant jusqu&#39;à la pointe touche la surface du site d&#39;impact. Ensuite, réglez le canal de Z sur le panneau de contrôle stéréotaxique à zéro. </li><li> Rétracter la pointe de frappetout en bougeant l&#39;actionneur vers le bas de 1 mm. </li><li> Appuyez sur le bouton de l&#39;impact de grève le site de la lésion et d&#39;atteindre une profondeur de 1 mm de déformation. </li></ol> 4. Blessures fermeture du site <ol><li> Utilisez applicateurs de coton-tige pour enlever tout effet de sang après, mais ne touchez pas la zone de blessure. </li><li> Placez la souris sur un bloc chaud pour maintenir la température du corps. </li><li> Une fois le saignement a cessé, suturer la plaie fermée. Mettre l&#39;animal dans la cage propre et lui permettre de se remettre de la chirurgie la nuit sur le pavé chaud. </li><li> Administrer buprénorphine 0,05-0,10 mg / kg SQ chaque 8-12 heures pendant 2 jours après la chirurgie. </li></ol>

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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=A+controlled+cortical+impact+model+of+traumatic+brain+injury+in+the+rat.">A controlled cortical impact model of traumatic brain injury in the rat.</a> J Neurosci Methods. 39 (3), 253-262 (1991).</li><li>Scheff, S. W., Baldwin, S. 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=Morris+water+maze+deficits+in+rats+following+traumatic+brain+injury:+lateral+controlled+cortical+impact.">Morris water maze deficits in rats following traumatic brain injury: lateral controlled cortical impact.</a> J Neurotrauma. 14 (9), 615-627 (1997).</li><li>Smith, D. H., Soares, H. 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The authors have nothing to disclose.

Les étapes les plus importantes pour générer des succès TCC cohérentes en utilisant un système d&#39;impact magnétique électronique pour provoquer une CCI sont: 1) fixer de façon stable la tête de la souris dans le cadre stéréotaxique; 2) la génération de la même taille de la fenêtre de l&#39;os entre les souris et l&#39;enlèvement de l&#39;os sans endommager la dure-dessous pendant craniectomy; 3) positionner correctement la pointe de percussion dans le centre de la zone ouverte et établir le point z?...

Lésion cérébrale traumatique (TBI) est définie comme une altération de la fonction du cerveau, ou d&#39;autres preuves de la pathologie du cerveau, causée par une force extérieure 1. TCC restent un grave problème de santé à travers le monde, notamment aux États-Unis. Selon les Centers for Disease Control and Prevention, au moins 1,7 million de TCC se produisent chaque année aux Etats-Unis résultant de 30,5% de tous les décès liés à des blessures. En 2000, les coûts médicaux directs et les coûts indirects de la TCC ont totalisé un montant estimé à $ 76,5 milliards aux États-Unis seulement. Bien que les progrès technologiques et thérapeutiques depuis des décennies précédentes ont permis d&#39;améliorer la qualité et la durée de vie des personnes souffrant de TCC, aucune pharmaceutique efficace ou des traitements préventifs existent actuellement. En raison de la complexité et des effets de grande portée de TCC, y compris les lésions tissulaires, la mort cellulaire, et la dégénérescence de l&#39;axone, il n&#39;ya pas deux blessures sont identiques; donc, pas de modèle de TBI courant pour animaux reproduit fidèlementtous les aspects de TBI comme on le voit chez les humains. Cependant, les modèles animaux ne fournissent la capacité de produire des blessures presque identiques nécessaires pour enquêter sur divers effets de TBI avec l&#39;espoir de comprendre davantage les manifestations cliniques de la TCC. Le modèle commandé incidence cortical (CCI) utilise un système d&#39;impact pour fournir un impact physique à la dure-mère d&#39;un animal exposé. Il induit TCC allant de légère à sévère similaires à ceux rencontrés par les humains. Cette blessure a été caractérisée sur le furet 2 et a ensuite été adapté pour une utilisation chez le rat 3,4, souris 5-7, et les moutons 8. Depuis la première caractérisation, le site de la lésion a été placé à la fois au-dessus de la ligne médiane de 2,9 et le cortex latéral 10. CCI fournit une méthode facile et précise d&#39;enquêter sur les effets et les traitements potentiels pour les TCC. En plus du modèle de CCI, la percussion de fluide et la perte de poids sont des modèles de commonly utilisé pour produire les TCC. Cependant, ces modèles présentent des limitations, y compris les moins de contrôle sur les paramètres de blessures, produire des changements histopathalogical pas vu dans les TCC humaine, et une plus grande incidence de décès accidentel chez les souris 3,5,10. Le modèle de l&#39;onde de choc est également utilisé pour produire des TCC. Bien que le modèle de l&#39;onde de choc ne reproduit pas les changements observés histopathalogical suite d&#39;un choc mécanique, ce modèle ne produit précisément TCC rencontrées notamment par des militaires 11. Le modèle d&#39;impact cortical contrôlé est facile à contrôler grâce au contrôle précis de paramètres de déformation tels que le temps, la vitesse et la profondeur de l&#39;impact 5. Une telle précision permet de reproduire les blessures à peu près identiques à travers tout un groupe d&#39;animaux plus réalisables. Plus important encore, la CCI reproduit TCC avec des caractéristiques observées dans les TCC humaine 12. Cependant, il n&#39;existe pas de modèle animal unique qui est tout à fait réussi à reproduire le spectre complet de pathologique changes observés après TBI. D&#39;autres recherches sont nécessaires pour révéler pleinement les changements aigus et chroniques qui se produisent après TBI. Deux types de blessures surviennent après un TCC: blessures primaires et secondaires. La lésion primaire se produit au moment de l&#39;impact et n&#39;est pas sensible à des traitements thérapeutiques; Toutefois, les blessures secondaires qui persistent après la blessure initiale sont soumis à des traitements 13. Le modèle d&#39;impact corticale contrôlée produit la lésion primaire, permettant ainsi aux chercheurs d&#39;étudier les effets de la TCC et traitements thérapeutiques potentiels pour les effets potentiellement durables de blessures secondaires. Les domaines de recherche potentiel en utilisant le modèle de la CCI comprennent la mort neuronale, l&#39;oedème cérébral, la neurogenèse, effets vasculaires, les changements histopathalogical, et les déficits de mémoire et plus 3,13-16.

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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>
		</tr>
		<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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			<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>
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			<td height="27" style="height:27px;width:247px;">forcept</td>
			<td style="width:171px;">Fine Science Tools</td>
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			<td>Surgery</td>
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			<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>
		</tr>
		<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>
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		<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.

Le modèle d&#39;impact corticale contrôlée produit TCC allant de sévérité légère à sévère. Après l&#39;impact de la quantité de gonflement crânien, hémorragie, et la distorsion du crâne sur le site de l&#39;impact, révéler la gravité des blessures résultant des paramètres de vitesse et de profondeur de déformation. TCC légers se traduisent par un gonflement crânien sur le site d&#39;impact et un léger saignement en raison de la violation de la durée limitée. Un TCC modéré présente gonflemen...

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.

Contrôlée corticale modèle d&#39;impact pour 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, ...

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

Research

JoVE Journal

Medicine

28.4K vues.  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.

Vidéo: 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.

La ventilation à pression contrôlée pour induire lésion pulmonaire aiguë chez la souris

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

Recherche

Médecine

Intraspinal Cell Transplantation for Targeting Cervical Ventral Horn in Amyotrophic Lateral Sclerosis and Traumatic Spinal Cord Injury

Respiratory compromise due to phrenic motor neuron loss is a debilitating consequence of a large proportion of human traumatic spinal cord injury (SCI) cases 1 and is the ultimate cause of death in patients with the motor neuron disorder, amyotrophic laterals sclerosis (ALS) 2.
ALS is a devastating neurological disorder that is characterized by relatively rapid degeneration of upper and lower motor neurons. Patients ultimately succumb to the disease on average 2-5 years following diagnosis because of respiratory paralysis due to loss of phrenic motor neuron innnervation of the diaphragm 3. The vast majority of cases are sporadic, while 10% are of the familial form. Approximately twenty percent of familial cases are linked to various point mutations in the Cu/Zn superoxide dismutase 1 (SOD1) gene on chromosome 21 4. Transgenic mice 4,5 and rats 6 carrying mutant human SOD1 genes (G93A, G37R, G86R, G85R) have been generated, and, despite the existence of other animal models of motor neuron loss, are currently the most highly used models of the disease.
Spinal cord injury (SCI) is a heterogeneous set of conditions resulting from physical trauma to the spinal cord, with functional outcome varying according to the type, location and severity of the injury 7. Nevertheless, approximately half of human SCI cases affect cervical regions, resulting in debilitating respiratory dysfunction due to phrenic motor neuron loss and injury to descending bulbospinal respiratory axons 1. A number of animal models of SCI have been developed, with the most commonly used and clinically-relevant being the contusion 8.
Transplantation of various classes of neural precursor cells (NPCs) is a promising therapeutic strategy for treatment of traumatic CNS injuries and neurodegeneration, including ALS and SCI, because of the ability to replace lost or dysfunctional CNS cell types, provide neuroprotection, and deliver gene factors of interest 9.
Animal models of both ALS and SCI can model many clinically-relevant aspects of these diseases, including phrenic motor neuron loss and consequent respiratory compromise 10,11. In order to evaluate the efficacy of NPC-based strategies on respiratory function in these animal models of ALS and SCI, cellular interventions must be specifically directed to regions containing therapeutically relevant targets such as phrenic motor neurons. We provide a detailed protocol for multi-segmental, intraspinal transplantation of NPCs into the cervical spinal cord ventral gray matter of neurodegenerative models such as SOD1G93A mice and rats, as well as spinal cord injured rats and mice 11.

Neural precursor transplantation is a promising strategy for protecting and/or replacing lost/dysfunctional cervical phrenic motor neurons in spinal cord injury (SCI) and the motor neuron disorder, amyotrophic laterals sclerosis (ALS). We provide a protocol for cell delivery to cervical spinal cord ventral horn in rodent models of ALS and SCI.

Cell Transplantation intraspinale pour le ciblage du col corne ventrale de la sclérose latérale amyotrophique et les lésions de la moelle épinière

Respiratory compromise due to phrenic motor neuron loss is a debilitating consequence of a large proportion of human traumatic spinal cord injury (SCI) ...

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.

Contrôlé blessures de lacération du col chez la souris

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.

Étirer dans le cerveau cellules endothéliales microvasculaires (CEND) comme<em&gt; In Vitro</em&gt; Traumatisme modèle du cerveau de la barrière hémato-encéphalique

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.

Rénale ischémie reperfusion: un modèle de souris de la blessure et de la régénération

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.

Un modèle Roman de lésions cérébrales traumatiques légères pour les jeunes rats

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.

Calibré Forceps modèle de compression de la moelle épinière des blessures

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.

Un modèle de lésion de la moelle épinière à base de déplacement tissulaire à base de tissus chez les souris

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.

Un modèle de souris de blessures cérébrales traumatiques légères et répétitives légères

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.

Évaluation semi-quantitative à l’aide de traceurs FDG [18F] chez les Patients atteints de lésions cérébrales graves

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