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

Questo lavoro è stato sostenuto da un finanziamento della Cord Indiana spinale &amp; Brain Injury Research Grants (SCBI 200-12), Ralph W. e Grazia M. Showalter Research Award, Indiana University ricerca biologica Grant, NIH sovvenzioni RR025761 e 1R21NS072631-01A.

Animal Care Maschile C57 BL / 6 topi erano alloggiato in gruppo e conservati in 12/12 ore di luce / buio ciclo con libero di accedere a cibo e acqua ad libitum. Gli animali utilizzati in questo protocollo sono di 10-12 settimane di età. Tutte le procedure sono state eseguite secondo protocolli approvati dalla cura degli animali e uso commissione di Indiana University. 1. Preparazione chirurgica <ol><li> Anestetizzare il mouse usando una miscela di ketamina / xilazina (87,7 mg / ml ketamina e 12,3 mg / ml Xylazina) e somministrare (1 ml / kg) tramite iniezione IP. </li><li> Radersi la testa del topo tra le orecchie. </li><li> Applicare una gelatina a base di petrolio agli occhi del mouse per prevenire l&#39;essiccazione durante la chirurgia. </li><li> Pulire la zona rasata con il 10% di iodio. Quindi utilizzare il 70% di etanolo per pulire lo iodio. </li><li> Fissare la testa del mouse nel frame stereotassico utilizzando le barre di auricolari e piastra morso. Assicurarsi che il cervello è stabile. </li></ol> 2. Craniectomy </p&gt; <ol><li> Effettuare una incisione longitudinale nel mezzo della testa con le forbici. Utilizzare una pinza emostatica per tenere la pelle fuori al lato sinistro. </li><li> Utilizzare un applicatore con punta di cotone per rimuovere il sangue e tessuto sull&#39;osso per esporre il cranio. Lasciare cranio esposto ad asciugare per 1 min. </li><li> Usare pinze per applicare la pressione e far sì che il cranio rimane immobile. Identificare punti di repere anatomici Lambda (aspetto caudale) e Bregma (aspetto frontale). Disegnare un cerchio al centro di Lambda e Bregma con un diametro di 4 mm di distanza dalla linea mediana 0,5 mm. </li><li> Usare un trapano per tagliare lungo il cerchio marcato. Soffiare delicatamente la polvere di osso di distanza. Non forare completamente attraverso l&#39;osso per evitare di danneggiare la dura madre. </li><li> Usare pinze per rimuovere l&#39;osso ed esporre la dura madre. </li></ol> 3. Impaction Il sistema impatto comprende una scatola di controllo per impostare i parametri di impatto, un attuatore per eseguire l&#39;occlusione, e un telaio stereotassico per fissare l&#39;attouator e la testa del mouse per l&#39;impatto. <ol><li> Pre-impostare la velocità dell&#39;attuatore di 3 m / sec prima dell&#39;intervento chirurgico. </li><li> Pre-set profondità della deformazione diverso da indurre diversi livelli di gravità del pregiudizio. Profondità di deformazione di 0,0-0,2 mm, 0,5-1,0 mm, e 1,2-2,0 mm si tradurrebbe in TBIs lieve, moderata e grave, rispettivamente. Questo protocollo spiegato come ottenere una lesione cerebrale moderatamente grave deformazione con una profondità di 1 mm, utilizzando una velocità di 3 m / sec. </li><li> Fissare l&#39;attuatore al titolare nel telaio stereotassico e utilizzare i micromanipolatori spostandolo per fissare il turno, punta piatta dell&#39;attuatore (diametro 3 mm) nel centro dell&#39;area cranio aperto. Quindi regolare la punta con un angolo parallelo alla superficie del sito di impatto. </li><li> Stabilire il punto zero spostando verso il basso l&#39;attuatore nel modello di proroga fino a toccare la superficie del sito di impatto. Quindi impostare il canale Z sul pannello di controllo stereotassica a zero. </li><li> Ritrarre la punta di simulazionementre simultaneamente spostando l&#39;attuatore giù 1 mm. </li><li> Premi il pulsante impatto di colpire il sito di lesione e di raggiungere una profondità di deformazione di 1 mm. </li></ol> 4. Lesioni sito Chiusura <ol><li> Utilizzare applicatori di cotone con punta per eliminare l&#39;eventuale impatto di sangue in seguito, ma non toccare la zona ferita. </li><li> Posizionare il mouse su un tappetino caldo per mantenere la temperatura corporea. </li><li> Una volta emorragia si è fermata, suturare la ferita chiusa. Mettere l&#39;animale nella gabbia pulita e permettono di recuperare da un intervento chirurgico durante la notte sul pad caldo. </li><li> Somministrare Buprenorfina 0,05-0,10 mg / kg SQ ogni 8-12 ore per 2 giorni dopo l&#39;intervento. </li></ol>

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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.

Le fasi più critiche per la generazione di successo TBIs coerenti con un sistema elettronico di impatto magnete di causare una CCI sono: 1) stabilmente fissa la testa del mouse nel frame stereotassico; 2) generare la stessa dimensione della finestra ossea tra topi e rimuovendo l&#39;osso senza danneggiare la dura sotto in caso craniectomy; 3) posizionare correttamente la punta impatto nel centro della zona aperta e fissazione del punto zero prima di colpire. Una testa mouse deve essere fiss...

Lesione cerebrale traumatica (TBI) è definita come una alterazione nella funzione del cervello, o altro titolo di patologia cerebrale, causata da una forza esterna 1. TBIs rimangono un grave problema di salute in tutto il mondo, in particolare negli Stati Uniti. Secondo i Centers for Disease Control and Prevention, almeno 1,7 milioni di TBI si verificano ogni anno negli Stati Uniti con conseguente 30,5% di tutti i decessi lesioni correlate. Nel 2000, i costi medici diretti e costi indiretti di TBI ammontano a una cifra stimata 76,5 miliardi dollari nei soli Stati Uniti. Nonostante i progressi tecnologici e terapeutici in decenni precedenti hanno migliorato la qualità e la durata della vita per chi soffre di TBI, non farmaceutica efficace o trattamenti preventivi esistono attualmente. A causa della complessità e effetti di vasta portata di TBI, comprese lesioni tessutali, morte cellulare e degenerazione dell&#39;assone, non esistono due ferite sono identici; quindi, nessun modello TBI corrente per gli animali riproduce fedelmentetutti gli aspetti della TBI come si è visto negli esseri umani. Tuttavia, i modelli animali forniscono la capacità di produrre danni quasi identici necessari per indagare i vari effetti di TBI con la speranza di comprendere ulteriormente le manifestazioni cliniche della TBI. L&#39;impatto corticale (CCI) modello controllato utilizza un sistema di impatto per fornire impatto fisico a dura esposta di un animale. Induce TBI che vanno da lievi a gravi simili a quelle sperimentate dagli esseri umani. Questa lesione è stato caratterizzato nella furetto 2 ed è stato successivamente adattato per l&#39;uso nel ratto 3,4, mouse 5-7, pecore e 8. Poiché la prima caratterizzazione, il sito della lesione è stato posto sia sulla linea mediana 2,9 e la corteccia laterale 10. CCI fornisce un metodo semplice e preciso di indagare gli effetti e trattamenti potenziali per TBI. Oltre al modello CCI, la percussione fluido e peso goccia modelli sono commonly utilizzato per produrre TBI. Tuttavia, questi modelli limitazioni presenti, tra cui un minore controllo sui parametri di pregiudizio, producendo cambiamenti histopathalogical non si vedono in TBIs umano e una maggiore incidenza di morte accidentale nei topi 3,5,10. Il modello di onda d&#39;urto è utilizzato anche per la produzione di TBI. Anche se il modello di onda d&#39;urto non riproduce le modifiche histopathalogical osservati a seguito di un impatto meccanico, questo modello non produce esattamente TBIs vissute in particolare da personale militare 11. Il modello controllato impatto corticale è facile da controllare a causa del controllo preciso su parametri di deformazione come il tempo, la velocità e la profondità di impatto 5. Tale precisione consente di replicare le lesioni quasi identici in un intero gruppo di animali più fattibile. Soprattutto, CCI riproduce TBIs con le caratteristiche viste in TBIs umano 12. Tuttavia, non esiste un modello unico animale che è del tutto riuscito a riprodurre la gamma completa di patologico chanGES si osservano dopo il trauma cranico. Ulteriori ricerche sono necessarie per rivelare pienamente le modifiche acute e croniche che si verificano dopo TBI. Due tipi di lesioni si verificano in seguito a un trauma cranico: le lesioni primarie e secondarie. La lesione primaria si verifica al momento dell&#39;impatto e non è sensibile ai trattamenti terapeutici; tuttavia, le lesioni secondarie che persistono dopo la lesione iniziale vengono sottoposti a trattamenti 13. Il modello controllato impatto corticale produce la lesione primaria, permettendo così ai ricercatori di indagare gli effetti del trauma cranico e potenziali trattamenti terapeutici per i potenziali effetti di lunga durata di lesioni secondarie. Aree di potenziale di ricerca utilizzando il modello di CCI sono morte neuronale, edema cerebrale, neurogenesi, effetti vascolari, i cambiamenti histopathalogical e deficit di memoria e più 3,13-16.

<table><tbody><tr><td>Povidone-iodine 7.5%</td><td>Purdue product L.P.</td><td></td><td>Surgical scrub</td></tr><tr><td>Cotton tipped applicators</td><td>Henry Schein</td><td>100-6015</td><td>Remove blood and debris</td></tr><tr><td>Scissor</td><td>Fine Science Tools</td><td>14084-08</td><td>Surgery</td></tr><tr><td>Forcept</td><td>Fine Science Tools</td><td>11293-00</td><td>Surgery</td></tr><tr><td>Hemostat</td><td>Fine Science Tools</td><td>13021-12</td><td>Surgery</td></tr><tr><td>Rechargeable Cordless Micro Drill</td><td>Stoelting</td><td>58610</td><td>Combine with Burrs for generating the bone window</td></tr><tr><td>Burrs for Micro Drill</td><td>Fine Science Tools</td><td>19007-05</td><td></td></tr><tr><td>Suture monofilament</td><td>Ethicon</td><td>G697</td><td>Suture</td></tr><tr><td>tert-Amyl alcohol</td><td>Sigma</td><td>152463-250ML</td><td>Making 2.5% Avertin</td></tr><tr><td>2,2,2-Tribromoethanol</td><td>Sigma</td><td>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.

Il modello di impatto corticale controllata produce TBI variano in gravità da lieve a grave. Post-impatto la quantità di gonfiore cranico, emorragia, e la distorsione cranica nel sito di impatto riveleranno la gravità del pregiudizio derivante dai parametri di velocità e profondità di deformazione. TBI Lieve producono gonfiore cranica presso il sito di impatto e leggero sanguinamento dovuto alla violazione durata limitata. Un trauma cranico moderato presenta gonfiore cranica e aumentato sanguinamento dovuto alla du...

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.

Controllata corticale modello Impact per trauma cranico

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

28.5K Views.  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.

Video: 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.

Modello di impatto corticale controllato di lesioni cerebrali del topo con trapianto terapeutico di cellule neurali derivate da cellule staminali indotte dall'uomo

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

Ricerca

Biologia dello sviluppo

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.

Un ripetitivo Concussive trauma cranico Modello nei topi

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

Medicina

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 modello di mouse del singolo e ripetitivo dolore cerebrale traumatico lieve

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.

Modello Murine di impatto corticale controllato per l'induzione di lesioni cerebrali traumatiche

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

Neuroscienze

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.

Modello di onda d'esplosione a bassa intensità per la valutazione preclinica della lesione cerebrale traumatica lieve a testa chiusa nei roditori

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>Un modello preclinico di impatto corticale controllato per emorragia traumatica, contusione e neuroinfiammazione

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.

Un modello preclinico di impatto corticale controllato per emorragia traumatica, contusione e neuroinfiammazione

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.

Modello elettromagnetico controllato a testa chiusa di lieve lesione cerebrale traumatica nei topi

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.

Valutazione dei cambiamenti nella plasticità sinaptica utilizzando un modello di trauma cranico chiuso sveglio di lieve lesione cerebrale traumatica

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

Induzione di rmTBI nei topi tramite un metodo di lesione a testa chiusa

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.

Autore in primo piano: Ottimizzazione dei modelli di roditori per lo studio dei meccanismi e della riabilitazione nelle lesioni cerebrali traumatiche lievi ripetute

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.

Modello murino modificato di lesione cerebrale traumatica lieve ripetitiva che incorpora finestra cranica assottigliata e percussione fluida

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

Controllata corticale modello Impact per trauma cranico

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