This works was supported by funding from a Florida Health grant (Brain and spinal cord injury research fund) (KKW).

Tutte le procedure sono state eseguite secondo protocolli # 201.207.692 approvato dal comitato di Cura e uso istituzionale degli animali della University of Florida e secondo il National Institutes of Health Guide per la Cura e l&#39;Utilizzo di animali da laboratorio. 1. Animal Care <ol><li> Utilizzare 3-4 mesi di età maschi 6J / C57BL. Fornire biancheria, materiale di nidificazione, cibo e acqua ad libitum. Mantenere i topi in temperatura ambiente controllata a 20 - 22 ° C con la luce / 12-hr cicli scuri 12 hr costanti. </li></ol> 2. Pre-compressione Preparazione <ol><li> Collegare un silicone gommato punta in metallo su misura per un dispositivo elettromagnetico impatto stereotassico. Assicurarsi che il fondo piatto della punta è parallelo alla superficie della punta della sonda (Figura 1A). </li><li> Anestetizzare il mouse con il 4% isoflurano seguita da anestesia di mantenimento del 2,5% isoflurano. Controllare l&#39;anestesia con flussimetro. Monitor livello anestesia finché l&#39;animale raggiunge un livello chirurgica di anestesia mostrando perdita del pedale recesso reflex. </li><li> Mettere il mouse in posizione prona su una piastra elettrica. Utilizzare un cono a forma di imbuto per mantenere il mouse in anestesia. Completamente radersi la testa con un trimmer. Utilizzare vaselina pomata oftalmica sugli occhi del topo per prevenire la secchezza mentre sotto anestesia. </li></ol> 3. I parametri di impatto Impostazione NOTA: Il sistema di impatto comprende una scatola di controllo per impostare i parametri di impatto, un attuatore per eseguire l&#39;occlusione, e una cornice stereotassico digitale con 3 assi di movimento. <ol><li> Pre-impostare la velocità del dispositivo di impatto a 4 m / sec e tempi a 240 msec sulla scatola di controllo. </li></ol> 4. Posizionamento del Centro Impact <ol><li> Mettere una piastra elettrica morbido sotto il corpo dell&#39;animale per mantenere la temperatura corporea vicino a 39 ° C. Montare il mouse in una cornice stereotassica in una prone posizione con le barre orecchio smussato-end. </li><li> Abbassare la punta impatto vicino alla testa del mouse spostando il Z-driver. Regolare la punta piatta impatto (diametro 9 mm) spostando il X e Y piloti a metà strada per le coordinate di destinazione al di sopra della sutura sagittale. </li><li> Assicurarsi che un bordo della punta impatto verticalmente parallela a una linea orizzontale immaginaria tracciata tra le due orecchie (Figura 1C). Il centro di impatto corrisponde alla metà sutura sagittale centrale tra suture interfrontal e lambdoid (interaurali 9 mm a Interaural 0 millimetri, 4,5 millimetri laterale). </li></ol> 5. Impatto Profondità Impostazione <ol><li> Per impostare correttamente la profondità dell&#39;impatto, utilizzare ulteriore punta della sonda per sostituire la gomma rivestita punta impatto silicone isolamento. </li><li> Per assicurarsi che non vi è alcun spostamento del centro impatto dopo punte di commutazione, impostare il X e il canale Y sul pannello di controllo stereotassico digitale a zero prima di passare le punte. </li><li> Spostare il probe punta al centro della zona di impatto spostando manualmente i-drive Y X-e. </li><li> sonda a contatto clip di coda del mouse. </li><li> Spostare il dispositivo di simulazione (unità Z) verso il basso fino a quando la punta della sonda tocca la superficie del sito di impatto. </li><li> Impostare il canale Z sul pannello di controllo stereotassico a zero. </li><li> Spostare la punta impatto di nuovo alla zona di impatto regolando manualmente X e Y-driver (non il pulsanti a zero sul pannello di controllo stereotassico digitale) fino a quando X e Y driver sono pari a zero (dove la punta impatto è stato posizionato in precedenza). </li><li> Ritrarre l&#39;attuatore spostando l&#39;interruttore di ritrazione sulla scatola di controllo. Spostare manualmente il dispositivo di simulazione verso il basso (driver Z) da 4 mm. </li></ol> 6. Impatto <ol><li> Innescare l&#39;impatto cliccando l&#39;interruttore impatto sulla scatola di controllo e di raggiungere una profondità di deformazione di 4 mm. </li></ol> 7. Post-occlusione <ol><li> Misurare il tempo per l&#39;impatto fino primo respiro del mouse utilizzando un timer. </li><li&gt; Rimuovere l&#39;animale dallo strumento e metterli su un pad caldo per mantenere la loro temperatura corporea. Non lasciare l&#39;animale incustodito fino a quando non ha ripreso conoscenza sufficiente a mantenere decubito sternale. </li><li> Consentire il recupero prima di tornare l&#39;animale di nuovo in una gabbia pulita. Non restituire un animale alla compagnia di altri animali fino alla completa guarigione. </li><li> Osservare e pesare i topi quotidiano. Se i topi mostrano segni di dolore, per via intraperitoneale li iniettare con Meloxicam a 1-2 mg / kg ogni 12 - 24 ore. </li></ol> 8. Impaction ripetitivo <ol><li> Dare i topi lesioni aggiuntive nei giorni 4, 7, e 10 dopo la lesione iniziale (intervallo di 72 ore tra impatti). </li></ol> 9. immunoistochimica (IHC) <ol><li> perfusione transcardial <ol><li> Anestetizzare i topi tramite iniezione intraperitoneale con 200 m / pentobarbital kg. </li><li> Valutare e garantire chirurgica piano anestesia da un pizzico dito del piede. secondoure il mouse in posizione supina con nastro adesivo delicatamente le zampe anteriori e le zampe posteriori per una superficie di lavoro di polistirolo all&#39;interno di una cappa. </li><li> Fare un&#39;incisione attraverso la pelle lungo la linea mediana del torace da appena sotto il processo xifoideo alla clavicola. Fare due incisioni cutanee aggiuntivi al processo xifoideo e procedere lungo la base della gabbia toracica ventrale laterale. </li><li> Aprire la cavità toracica e esporre il cuore tagliando attraverso la muscolatura del torace e costole. </li><li> Fissare il cuore pulsante con una pinza smussato e fare un 1 - mm incisione 2 nel ventricolo sinistro. </li><li> Inserire immediatamente un ago a farfalla nell&#39;atrio destro. Iniziare l&#39;infusione di 20 ml di soluzione salina spingendo la siringa lentamente. </li><li> Passare dalla soluzione salina al 4% paraformaldeide. Continuare perfusione con 20 ml di paraformaldeide. </li><li> Decapitare il mouse e togliere la pelle con le forbici. Isolare il cervello dal cranio con un cutter osso. </li></ol></li><li> Cryostat sezionamento <ol><li> tessuti cerebrali Incorpora in temperatura di taglio (OCT) formulazione e congelamento ottimale a -80 ° C. Posizionare il cervello nel criostato in un orientamento sagittale. sezioni di cervello Cut 5 micron di spessore. </li></ol></li><li> colorazione <ol><li> Asciugare le sezioni congelate a temperatura ambiente per 1 ora. </li><li> Incubare i vetrini con 100 ml di 2% siero di capra e 0,1% Triton X-100 in tampone fosfato salino (PBS) per 1 ora a temperatura ambiente. </li><li> Lavare i vetrini 3 volte con 300 ml di PBS. Poi incubare i vetrini con anti-GFAP (1: 200) o anticorpo anti-ferritina (1: 200) separatamente per una notte a 4 ° C. </li><li> Lavare i vetrini 3 volte con 300 ml di PBS. Poi incubare i vetrini per 2 ore a temperatura ambiente con anticorpo secondario biotina-coniugato. </li><li> Lavare i vetrini 3 volte con 300 ml di PBS. Poi incubare i vetrini con soluzione avidina-biotina complesso (ABC) (1:50) a temperatura ambiente per 30 min. </li><li>Lavare i vetrini 3 volte con 300 ml di PBS. Poi incubare in 3,3&#39;-diaminobenzidina soluzione (DAB) substrato (50 ml PBS, 10 microlitri H 2 O 2, 10 mg DAB pillola, filtro prima dell&#39;uso) per 5 - 8 min. Osservare i vetrini al microscopio fino a quando compaiono le cellule positive. </li><li> Sciacquare i vetrini in acqua di rubinetto corsa lenta per 5 min. diapositive pulite con un laboratorio-wipe. Quindi montare le sezioni con mezzo di montaggio e vetrino. </li></ol></li></ol>

<ol><li>Baugh, C. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Chronic+traumatic+encephalopathy%3A+neurodegeneration+following+repetitive+concussive+and+subconcussive+brain+trauma%5BTitle%5D)+AND+%22Brain+Imaging+Behav%22%5BJournal%5D)">Chronic traumatic encephalopathy: neurodegeneration following repetitive concussive and subconcussive brain trauma.</a> Brain Imaging Behav. 6 (2), 244-254 (2012).</li>
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<li>Petraglia, A. L., Dashnaw, M. L., Turner, R. C., Bailes, J. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Models+of+mild+traumatic+brain+injury%3A+translation+of+physiological+and+anatomic+injury%5BTitle%5D)+AND+%22Neurosurgery%22%5BJournal%5D)">Models of mild traumatic brain injury: translation of physiological and anatomic injury.</a> Neurosurgery. 75 Suppl (4), S34-S49 (2014).</li>
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<li>Gold, E. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Functional+assessment+of+long-term+deficits+in+rodent+models+of+traumatic+brain+injury%5BTitle%5D)+AND+%22RegenMed%22%5BJournal%5D)">Functional assessment of long-term deficits in rodent models of traumatic brain injury.</a> RegenMed. 8 (4), 483-516 (2013).</li>
<li>Xiong, Y., Mahmood, A., Chopp, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Animal+models+of+traumatic+brain+injury%5BTitle%5D)+AND+%22Nat+Rev+Neurosci%22%5BJournal%5D)">Animal models of traumatic brain injury.</a> Nat Rev Neurosci. 14 (2), 128-142 (2013).</li>
<li>Luo, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Long-term+cognitive+impairments+and+pathological+alterations+in+a+mouse+model+of+repetitive+mild+traumatic+brain+injury%5BTitle%5D)+AND+%22Front+Neurol%22%5BJournal%5D)">Long-term cognitive impairments and pathological alterations in a mouse model of repetitive mild traumatic brain injury.</a> Front Neurol. , 5-12 (2014).</li>
<li>Yang, Z., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Temporal+MRI+characterization%2C+neurobiochemical+and+neurobehavioral+changes+in+a+mouse+repetitive+concussive+head+injury+model%5BTitle%5D)+AND+%22Sci+Rep%22%5BJournal%5D)">Temporal MRI characterization, neurobiochemical and neurobehavioral changes in a mouse repetitive concussive head injury model.</a> Sci Rep. 10 (5), 11178(2015).</li>
<li>Zhang, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Inhibition+of+monoacylglycerol+lipase+prevents+chronic+traumatic+encephalopathy-like+neuropathology+in+a+mouse+model+of+repetitive+mild+closed+head+injury%5BTitle%5D)+AND+%22J+Cereb+Blood+Flow+Metab%22%5BJournal%5D)">Inhibition of monoacylglycerol lipase prevents chronic traumatic encephalopathy-like neuropathology in a mouse model of repetitive mild closed head injury.</a> J Cereb Blood Flow Metab. 35 (3), 443-453 (2015).</li>
<li>Petraglia, A. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((The+spectrum+of+neurobehavioral+sequelae+after+repetitive+mild+traumatic+brain+injury%3A+a+novel+mouse+model+of+chronic+traumatic+encephalopathy%5BTitle%5D)+AND+%22J+Neurotrauma%22%5BJournal%5D)">The spectrum of neurobehavioral sequelae after repetitive mild traumatic brain injury: a novel mouse model of chronic traumatic encephalopathy.</a> J Neurotrauma. 31 (13), 1211-1224 (2014).</li>
<li>Lumpkins, K. M., Bochicchio, G. V., Keledjian, K., Simard, J. M., McCunn, M., Scalea, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Glial+fibrillary+acidic+protein+is+highly+correlated+with+brain+injury%5BTitle%5D)+AND+%22J+Trauma%22%5BJournal%5D)">Glial fibrillary acidic protein is highly correlated with brain injury.</a> J Trauma. 65 (4), 778-782 (2008).</li>
<li>Yang, Z., Wang, K. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Glial+fibrillary+acidic+protein%3A+from+intermediate+filament+assembly+and+gliosis+to+neurobiomarker%5BTitle%5D)+AND+%22Trends+Neurosci%22%5BJournal%5D)">Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker.</a> Trends Neurosci. 38 (6), 364-374 (2015).</li>
<li>Liu, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Increased+expression+of+ferritin+in+cerebral+cortex+after+human+traumatic+brain+injury%5BTitle%5D)+AND+%22Neurol+Sci%22%5BJournal%5D)">Increased expression of ferritin in cerebral cortex after human traumatic brain injury.</a> Neurol Sci. 34 (7), 1173-1180 (2013).</li>
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</ol>

The authors have no financial interest to disclose.

Per simulare le lesioni cerebrali morfologicamente simili alle condizioni cliniche, sono attesi i sintomi post-commozione cerebrale. sintomi post-commozione cerebrale generalmente includono mal di testa, capogiri, vertigini, stanchezza, problemi di memoria e di sonno, difficoltà di concentrazione così come ansia e umore depresso. Dal momento che i sintomi somatici non possono ancora essere misurabile in modelli animali, i cambiamenti del motore e la funzione cognitiva e il comportamento emotivo sono utilizzati come cr...

Commozione cerebrale, chiamata anche lievi lesioni cerebrali traumatiche (mTBI), è la presenza più frequente di lesione cerebrale traumatica (TBI) e colpisce milioni di persone in Stati Uniti. Commozioni può essere difficile da diagnosticare e non esiste una cura specifica per commozione cerebrale. Vi è un crescente riconoscimento e alcune prove che lievi traumi meccanici derivanti da infortuni sportivi, combattimento militare, e altre attività fisicamente coinvolgenti può avere conseguenze cumulativi e croniche neurologiche 1,2. Tuttavia, vi è ancora una mancanza di conoscenza per quanto riguarda traumi e dei loro effetti. metodologia attuale limita gli studi di patologia e trattamento negli esseri umani dal momento che solo la valutazione neurologica e la valutazione di imaging sono disponibili per la diagnosi clinica. Modelli animali forniscono un mezzo per studiare traumi in modo efficiente, rigorosa e controllata con la speranza di ulteriori diagnosi e il trattamento di mTBI. Gli studi hanno adattato tradizionale TBImodelli come impatto corticale controllata (CCI), l&#39;impatto del fluido-percussioni (FPI), lesioni calo di peso, e lesioni colpo di vento per eseguire mTBI e stimolare gravità bassi lesioni cambiando i parametri di lesioni. Questi modelli sono utili da usare grazie alla loro capacità di replicare trauma cerebrale morfologicamente simile alla condizione clinica; tuttavia, hanno anche i propri limiti. La gravità del danno indotto da un infortunio di accelerazione (calo di peso) è spesso molto variabile. I due risultati della CCI mite - emorragia subaracnoidea e contusione focale - non sono confrontabili con traumi tipici umani. ICC e FPI richiedono una craniotomia, che non è clinicamente rilevante, mentre la ferita esplosione è un modello più controverso per quanto riguarda i differenti misure di posizione di esposizione e di pressione di picco, così come danno secondario variabile durante l&#39;esposizione 3-6. Un modello animale concussive aggiornato in grado di tradurre la ricerca pre-clinica in Setti clinicang è necessario nella ricerca. La questione chiave nel modellare lieve trauma cranico è quello di definire la gravità delle lesioni sperimentale, che replica più strettamente l&#39;infortunio in un ambiente clinico. Recentemente, diversi gruppi di ricerca hanno sviluppato il trauma cranico chiuso o trauma cranico concussive (CHI) Modello 7-10. CHI è una modifica di CCI senza craniotomia, ma utilizza ancora un urto magnetico elettronico tradizionale per generare un impatto della testa. Un CHI può indurre un trauma cranico che vanno da lieve a moderata, regolando i parametri di impatto. Perdita di coscienza (LOC) può essere osservato immediatamente dopo un impatto rilevando una diminuzione del tasso di respirazione o la cessazione transitoria della respirazione. Il periodo di LOC è utilizzato per determinare la gravità delle lesioni. Questo documento comprende una versione leggermente migliorata e aggiornata di un modello ripetitivo CHI (rCHI) nei topi, insieme ad una dettagliata protocollo passo-passo e risultati rappresentativi. Il rCHI strategie di ricerca del modello dire utile nel determinare effetti mTBI e potenziali trattamenti, soprattutto dal momento che non esiste un modello singolo animale in grado di imitare tutti i concussione indotta cambiamenti patologici.

<table><tbody><tr><td>anesthesia machine</td><td>Eagle Eye Anesthesia, Inc</td><td>Model 150&amp;nbsp;</td><td>anesthesia</td></tr><tr><td>Electromagnetic Impactor</td><td>LeicaBiosystems</td><td>Impact One Stereotaxic Impactor</td><td>perform impaction</td></tr><tr><td>Digital Stereotaxic instrument</td><td>LeicaBiosystems</td><td>39462501</td><td>mount mouse and positioning tips</td></tr><tr><td>Sicilone rubber-coated metal tip</td><td>Precision Tool &amp;amp; Engineering, Gainesvill FL</td><td>custom-made</td><td>impact tip</td></tr><tr><td>Lithium Ion All-in-One Trimmer</td><td>WAHL Home Products</td><td>9854-600</td><td>shave mouse hair</td></tr><tr><td>paper clips</td><td>custom-made</td><td></td><td>probe tip</td></tr><tr><td>Cotton tipped applicators</td><td>MEDLINE</td><td>MDS202055</td><td>scrub head with saline</td></tr><tr><td>Tissue Tek O.C.T.</td><td>ASKURA FINETEK USA INC</td><td>4583</td><td>tissue embedding</td></tr><tr><td>anti-GFAP</td><td>Dako</td><td>CA93013</td><td>antibody for IHC</td></tr><tr><td>anti Ferritin</td><td>Sigma</td><td>F6136</td><td>antibody for IHC</td></tr><tr><td>VECTASTAIN Elite ABC&amp;nbsp; kit</td><td>Vector laboratories</td><td>PK-6100</td><td>IHC detection system</td></tr><tr><td>Permount Mounting Medium</td><td>Fisher Scientific</td><td>SP15-100</td><td></td></tr><tr><td>Aperio XT ScanScope scanner</td><td>Leica Microsystems Inc,</td><td></td><td>slides scanning</td></tr><tr><td>Leica AutoStainer XL</td><td>Leica the pathology Company</td><td>ST2010</td><td>H&amp;amp;E staining</td></tr><tr><td>DAB&amp;nbsp;</td><td>sigma</td><td>D3939</td><td>IHC detection system</td></tr></tbody></table>

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.

In questo modello (Figura 1 AC), ci sono stati brevi periodi di boccheggiare e respirazioni profonde. Una perdita di coscienza (inconscia) è definita come una diminuzione del tasso di respirazione o la cessazione della respirazione transitoria prima di riprendere una normale respirazione. Un impatto sul centro della testa ha causato perdita di coscienza di breve durata (7.5 ± 4.7, 7.8 ± 5.5, 10.2 ± 8.8, 9.5 ± 8.0 sec a ogni impatto separatamente, Figura 1D)....

Watch this Scientific Journal Video about A Repetitive Concussive Head Injury Model in Mice at JoVE.com

A Repetitive Concussive Head Injury Model in Mice

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 ...

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JoVE Journal

Medicine

11.9K Views.  University of Florida. 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.

Video: A Repetitive Concussive Head Injury Model in Mice

The Spared Nerve Injury (SNI) Model of Induced Mechanical Allodynia in Mice

Peripheral neuropathic pain is a severe chronic pain condition which may result from trauma to sensory nerves in the peripheral nervous system. The spared nerve injury (SNI) model induces symptoms of neuropathic pain such as mechanical allodynia i.e. pain due to tactile stimuli that do not normally provoke a painful response [1]. 
The SNI mouse model involves ligation of two of the three branches of the sciatic nerve (the tibial nerve and the common peroneal nerve), while the sural nerve is left intact [2]. The lesion results in marked hypersensitivity in the lateral area of the paw, which is innervated by the spared sural nerve. The non-operated side of the mouse can be used as a control. The advantages of the SNI model are the robustness of the response and that it doesn&#x2019;t require expert microsurgical skills.
The threshold for mechanical pain response is determined by testing with von Frey filaments of increasing bending force, which are repetitively pressed against the lateral area of the paw [3], [4]. A positive pain reaction is defined as sudden paw withdrawal, flinching and/or paw licking induced by the filament. A positive response in three out of five repetitive stimuli is defined as the pain threshold. 
As demonstrated in the video protocol, C57BL/6 mice experience profound allodynia as early as the day following surgery and maintain this for several weeks.

The Spared Nerve Injury SNI Model of Induced Mechanical Allodynia in Mice

The Spared Nerve Injury animal model is described here as a mouse model of peripheral neuropathic pain following partial denervation of the sciatic nerve by lesioning the tibial and common peroneal nerve branches, leaving the remaining sural nerve intact. Behavioral modification resulting from mechanical allodynia is quantified by von Frey filaments.

Risparmiato il Nerve pregiudizio (SNI) Modello di Allodinia meccanica indotta nei topi

Peripheral neuropathic pain is a severe chronic pain condition which may result from trauma to sensory nerves in the peripheral nervous system. The spared ...

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Medicina

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.

Controllata cervicale lesioni lacerazione nei topi

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

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 modello Novel di Mild Traumatic Brain Injury per ratti giovani

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

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 ...

A Novel and Translational Rat Model of Concussion Combining Force and Rotation with In Vivo Cerebral Microdialysis

Persistent cognitive and motor symptoms are known consequences of concussions/mild traumatic brain injury (mTBIs) that can be partly attributable to altered neurotransmission. Indeed, cerebral microdialysis studies in rodents have demonstrated an excessive extracellular glutamate release in the hippocampus within the first 10 min following trauma. Microdialysis offers the clear advantage of in vivo neurotransmitter continuous sampling while not having to sacrifice the animal. In addition to the aforementioned technique, a closed head injury model that exerts rapid acceleration and deceleration of the head and torso is needed, as such a factor is not available in many other animal models. The Wayne State weight-drop model mimics this essential component of human craniocerebral trauma, allowing the induction of an impact on the head of an unrestrained rodent with a falling weight. Our novel and translational rat model combines cerebral microdialysis with the Wayne State weight-drop model to study, in lightly anesthetized and unrestrained adult rats, the acute changes in extracellular neurotransmitter levels following concussion. In this protocol, the microdialysis probe was inserted inside the hippocampus as region of interest, and was left inserted in the brain at impact. There is a high density of terminals and receptors in the hippocampus, making it a relevant region to document altered neurotransmission following concussion. When applied to adult Sprague-Dawley rats, our combined model induced increases in hippocampal extracellular glutamate concentrations within the first 10 min, consistent with the previously reported post-concussion symptomology. This combined weight-drop model provides a reliable tool for researchers to study early therapeutic responses to concussions in addition to repetitive brain injury, since this protocol induces a closed-head mild trauma.

Neurotransmitter alteration is a mechanism of neural dysfunction that occurs after concussion and contributes to the sometimes-catastrophic long-term consequences. This rat model combines microdialysis, allowing in vivo neurotransmitter quantification, with a weight-drop technique exerting rapid acceleration and deceleration of the head and torso, an important factor of human craniocerebral trauma.

Un nuovo e traslazionale modello di commozione cerebrale che combina forza e rotazione con la microdialisi cerebrale in vivo

Persistent cognitive and motor symptoms are known consequences of concussions/mild traumatic brain injury (mTBIs) that can be partly attributable to ...

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 ...

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 ...

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 ...

Un ripetitivo Concussive trauma cranico Modello nei topi

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Un modello Novel di Mild Traumatic Brain Injury per ratti giovani

Un modello di mouse del singolo e ripetitivo dolore cerebrale traumatico lieve

Un nuovo e traslazionale modello di commozione cerebrale che combina forza e rotazione con la microdialisi cerebrale in vivo

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

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

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

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

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