Este trabalho é financiado pelo New Jersey Comissão de Pesquisa em Lesão Cerebral.

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J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lateral+fluid+percussion+brain+injury:+a+15-year+review+and+evaluation.">Lateral fluid percussion brain injury: a 15-year review and evaluation.</a> J Neurotrauma. 22, 42-75 (2005).</li><li>Hamm, R. J., Pike, B. R., O'Dell, D. M., Lyeth, B. G., Jenkins, L. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+rotarod+test:+an+evaluation+of+its+effectiveness+in+assessing+motor+deficits+following+traumatic+brain+injury.">The rotarod test: an evaluation of its effectiveness in assessing motor deficits following traumatic brain injury.</a> J Neurotrauma. 11, 187-196 (1994).</li><li>Scherbel, U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differential+acute+and+chronic+responses+of+tumor+necrosis+factor-deficient+mice+to+experimental+brain+injury.">Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury.</a> Proc Natl Acad Sci. 96, 8721-8726 (1999).</li><li>Morris, R. G., Garrud, P., Rawlins, J. N., O'Keefe, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Place+navigation+impaired+in+rats+with+hippocampal+lesions.">Place navigation impaired in rats with hippocampal lesions.</a> Nature. 297, 681-683 (1982).</li><li>Stichel, C. C., Muller, H. 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T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motor+and+cognitive+function+evaluation+following+experimental+traumatic+brain+injury.">Motor and cognitive function evaluation following experimental traumatic brain injury.</a> Neuroscience and biobehavioral reviews. 28, 365-378 (2004).</li><li>Carbonell, W. S., Maris, D. O., McCall, T., Grady, M. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Adaptation+of+the+fluid+percussion+injury+model+to+the+mouse.">Adaptation of the fluid percussion injury model to the mouse.</a> Journal of neurotrauma. 15, 217-229 (1998).</li></ol>

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O método apresentado aqui LFP muitos modelos dos resultados neuropathalogical e comportamentais de leve a moderada lesão cerebral traumática é por isso que tornou-se um modelo animal amplamente utilizado do TCE. Existem vários passos críticos a considerar a fim de aumentar a validade ea confiabilidade desta técnica. Por exemplo, é importante que os animais apenas em que a integridade da dura-máter não foi comprometida durante a craniectomia ser submetido a LFP e utilizados no estudo. Além disso, se a craniectomia é obstruída por qualquer cola ou cimento como a parte da dura abaixo da craniectomia não é exposto à força da pressão do fluido, o animal deve ser eliminado do estudo. Finalmente, se o tempo de reflexo de endireitamento ou a taxa de mortalidade não está dentro do intervalo desejado, o animal não deve ser incluído no estudo. A intensidade do pulso de pressão pode ser aumentada para gerar lesões mais graves. Conforme mostrado na Figura 1, a configuração do dispositivo de LFP é relativamente simples e reprodutibilidade do grau de lesão é mantida através do acompanhamento das atmosferas de pressão sobre o osciloscópio. A forma suave da curva no traçado osciloscópio indica que não há bolhas de ar no fluido que possam interferir com a indução da lesão LFP. Um pulso de teste deve ser entregue antes da indução de lesão e se o traço do osciloscópio não apresentam uma curva suave, as bolhas de ar deve ser removido. A duração do pulso é de aproximadamente 20 ms, que representa o tempo de indução medido em simulações de testes de colisão. Lesões de pulsos curtos são susceptíveis de produzir lesões mais focal. Portanto, essa duração de modelos de pulso humano TCE. As alterações morfológicas e celulares seguintes LFP incluem danos físicos para o tecido, assim como aumento do número de astrócitos e macrófagos como demonstrado na Figura 2. É bem estabelecido que um dos sinais de lesão característica é a hiperplasia dos astrócitos ea formação de uma cicatriz glial. A cicatriz glial foi mostrado para ter tanto efeitos benéficos e prejudiciais 24. Da mesma forma, os macrófagos são conhecidos por se acumular em vários tecidos durante a fase seguinte lesão quando o processo de cura começa 25. Assim, o aumento do número de GFAP e MAC1 células positivas nas amostras LFP em relação aos controles sham é um indicativo de indução de lesão. A falta de expressão desses marcadores celulares específicos nos controles sham indica que a manipulações cirúrgicas por si só não tem consequências negativas sobre a saúde do tecido cerebral e que as mudanças na expressão de proteínas são específicos para o paradigma lesão. As conseqüências comportamentais da LFP leve ilustrada na Figura 3 incluem déficits cognitivos e motor. As descobertas indicam que a MWM ratos LFP eventualmente aprender a tarefa, mas a um ritmo mais lento do que os ratos sham e eles não me lembro a tarefa bem um dia após o treinamento. Assim, mesmo os ratos levemente feridos são menos eficientes do que os ratos sham em usar estímulos externos para processar, consolidar e armazenar informações espaciais, que devem ser recuperadas durante os testes subseqüentes. Outros hipocampo-dependente tarefas cognitivas, tais como resposta de medo condicionado foram mostrados para ser prejudicada em camundongos submetidos a LFP 26. Finalmente, quanto menor a latência para queda de ratos LFP relação aos ratos sham no paradigma rotarod até 3 semanas após a lesão leve é ​​um indicador de déficits de vestibulomotor integrado e função sensório-motor. A lesão mais moderado iria revelar mudanças mais marcantes na função cognitiva e motora como tem sido demonstrado por outros grupos 27-30. Em suma, a LFP é um modelo válido para TBI humano, porque cumpre muitos dos critérios que o esperado. LFP fornece validade de construto na medida em que recria os processos etiológicos que induzem TCE em humanos. Especificamente, a magnitude da força e taxa de mortalidade é semelhante ao que ocorre no esporte leve e moderada e as lesões relacionadas a carros com a ressalva de que as intervenções pré-lesão cirúrgica são exclusivas para o modelo animal. LFP também apresenta validade de face, em que recapitula LFP muitos dos anatômicos, bioquímicos, os efeitos neuropatológicos e comportamentais observadas no TCE humana. Há duas alterações focais e difusas detectados após LFP ea lateralização do impacto permite que se compare os danos morfológicos no lado ipsilateral à lesão de que no lado contralateral. Uma ressalva é que os efeitos cognitivos e motor podem ser mais sutis, como resultado de ferir apenas um hemisfério. Finalmente, LFP apresenta validade preditiva ea confiabilidade da técnica LFP permite a avaliação de várias manipulações farmacológicas e genéticas antes ou após a indução da lesão 20. Variáveis ​​fisiológicas como a pressão arterial, o pH do sangue e do sanguegases precisam ser medidos na presença e ausência de uma droga de teste para determinar o mecanismo de ação de um agente terapêutico. No entanto, devido à natureza complexa das conseqüências primária e secundária da TBI, é uma tarefa difícil identificar uma única intervenção que pode mitigar todos os sintomas. Uma consideração futura para a técnica LFP pode ser o uso de micro-percussão líquido que emprega um instrumento controlado por microprocessador, pneumaticamente para eliminar a necessidade de calibrar a força entregue pelo pêndulo e para evitar variáveis ​​operacionais, tais como bolhas de ar no fluido 15 . No entanto, a abordagem LFP padrão tem sido comprovada por muitos pesquisadores de ser uma técnica confiável e simples para explorar os mecanismos moleculares subjacentes à danos e recuperação após o TCE que irá levar a melhor e intervenções terapêuticas.

<ul><li> Instrumento de alinhamento estereotáxico para ratos (Instrumentos Kopf) </li><li> Gás do mouse titular cabeça anestesia (Instruments Kopf) </li><li> Aparelho de anestesia com O 2 flush (Parkland Científica) </li><li> Aparelho de anestesia com O2 flush (Parkland Científica) </li><li> Buprenorphrine (Webster Abastecimento Animal) </li><li> Atualizar Lacri pomada Lube (Fisher) </li><li> Bupivacaína / Marcaine (Webster Abastecimento Animal) </li><li> Iodopovidona solução (Fisher) </li><li> 20 g 1 ½ &quot;agulhas (Becton Dickinson) </li><li> Lâmina de bisturi (# 15) e titular (Becton Dickinson) </li><li> Grampos Bulldog (Ferramentas Ciência Fine) </li><li> Ferramenta dental ou raspador de osso (Ferramentas Ciência Fine) </li><li> Lado segurando uma pinça Dumont n º 6 (Ferramentas Ciência Fine) </li><li> 3 milímetros de diâmetro exterior trefina (Investigação Loja Instrumentation, University of Pennsylvania) </li><li> Cabo de nylon sólido (1,7 mm de diâmetro, por exemplo, linha de trimmer erva daninha) </li><li> Super cola gel </li><li> Loctite cola de cianoacrilato (Loctite 444 Tak Pak) (Henkel Corporation) </li><li> Jet Líquido Acrílico (Butler Schein) </li><li> Resina Perm reembasamento / Reparação (Butler Schein) </li><li> Armazenamento osciloscópio TDS 1001B, 40 mHz, 500MS / s (Tektronix) </li><li> Trauma Indutor Amplificador transdutor de pressão (Custom Design e Fabricação, Virginia Commonwealth University) </li><li> LFP dispositivo (Design personalizado e Fabricação, Virginia Commonwealth University) </li><li> Tubulação de alta pressão, 41 centímetros de comprimento, 2 ml de volume (Baxter) </li><li> 3M Adesivo Vetbond Tissue (Fisher) </li></ul>

lateral fluid percussion: model of traumatic brain injury in mice

Traumatismo crânio-encefálico (TCE) investigação tem atingido impulso renovado devido à consciência crescente de lesões na cabeça, o que resulta em morbidade e mortalidade. Com base na natureza da lesão primária seguintes TBI, resultado conseqüências complexa e heterogênea secundário, que são seguidos por 1,2 processos regenerativos. Lesão primária pode ser induzida por uma contusão direto para o cérebro de fratura de crânio ou de cisalhamento e alongamento dos tecidos causando deslocamento do cérebro devido ao movimento de 3,4. Os hematomas e lacerações resultantes causar uma resposta vascular 3,5, e os danos morfológicos e funcionais da substância branca leva a lesão axonal difusa 6-8. Adicional alterações secundárias comumente observadas no cérebro são edema e aumento da pressão intracraniana 9. Seguintes TCE existem alterações microscópicas em vias bioquímicas e fisiológicas que envolvem a liberação de neurotransmissores excitotoxic, mediadores imunes e radicais de oxigênio 10-12, o que acaba resultado em longo prazo neurológicas 13,14. Assim, escolhendo modelos animais apropriados de TCE que apresentam semelhante eventos celulares e moleculares no TCE humanos e roedores é fundamental para estudar os mecanismos subjacentes lesão e reparo. Vários modelos experimentais de TCE foram desenvolvidos para reproduzir aspectos do TCE observados em humanos, entre eles três modelos específicos são amplamente adaptados para roedores: percussão fluido, o impacto cortical e aceleração de queda de peso / impacto 1. O dispositivo de percussão fluido produz uma lesão através de uma craniectomia pela aplicação de um pulso de pressão de fluido em breve para a dura-máter intacta. O pulso é criado por um pêndulo impressionante o pistão de um reservatório de fluido. A percussão produz deslocamento breve e deformação do tecido neural 1,15. Por outro lado, lesões impacto cortical fornece energia mecânica para a dura-máter intacta através de um pêndulo rígido sob pressão pneumática 16,17. O peso do modelo queda / impacto é caracterizada pela queda de uma haste com uma massa específica no crânio fechado 18. Entre os modelos de TCE, LFP é o modelo mais estabelecidos e comumente utilizada para avaliar lesão cerebral mista focal e difusa 19. É reprodutível e é padronizado para permitir a manipulação de parâmetros de lesão. Lesões recapitula LFP observada em seres humanos, tornando-la clinicamente relevantes, e permite a exploração de novas terapêuticas para a tradução clínica 20. Descrevemos o protocolo detalhado para realizar procedimento de LFP em camundongos. A contusão é leve a moderada, com regiões do cérebro como o córtex, hipocampo e corpo caloso sendo mais vulneráveis. Hipocampo e motor tarefas de aprendizagem são explorados seguintes LFP.

Watch this Scientific Journal Video about Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice at JoVE.com

Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

Lateral fluido percussão (LFP), um modelo estabelecido de lesão cerebral traumática em camundongos, é demonstrada. LFP preenche três critérios principais para modelos animais: relevância, fiabilidade, validade e clínicos. O procedimento, que consiste em craniotomia cirúrgico, a fixação do cubo seguida de indução de lesão, resultando em lesões focais e difusas, é descrito.

Percussão Fluid lateral: Modelo de Lesão em Ratos

Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and ...

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Neuroscience

40.4K visualizações.  University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School. Lateral fluido percussão (LFP), um modelo estabelecido de lesão cerebral traumática em camundongos, é demonstrada. LFP preenche três critérios principais para modelos animais: relevância, fiabilidade, validade e clínicos. O procedimento, que consiste em craniotomia cirúrgico, a fixação do cubo seguida de indução de lesão, resultando em lesões focais e difusas, é descrito.

Vídeo: Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

A Method to Inflict Closed Head Traumatic Brain Injury in Drosophila

Traumatic brain injury (TBI) affects millions of people each year, causing impairment of physical, cognitive, and behavioral functions and death. Studies using Drosophila have contributed important breakthroughs in understanding neurological processes. Thus, with the goal of understanding the cellular and molecular basis of TBI pathologies in humans, we developed the High Impact Trauma (HIT) device to inflict closed head TBI in flies. Flies subjected to the HIT device display phenotypes consistent with human TBI such as temporary incapacitation and progressive neurodegeneration. The HIT device uses a spring-based mechanism to propel flies against the wall of a vial, causing mechanical damage to the fly brain. The device is inexpensive and easy to construct, its operation is simple and rapid, and it produces reproducible results. Consequently, the HIT device can be combined with existing experimental tools and techniques for flies to address fundamental questions about TBI that can lead to the development of diagnostics and treatments for TBI. In particular, the HIT device can be used to perform large-scale genetic screens to understand the genetic basis of TBI pathologies.

A Method to Inflict Closed Head Traumatic Brain Injury in Drosophila

Here we describe a method to inflict closed head traumatic brain injury (TBI) in Drosophila. This method provides a gateway to investigate the cellular and molecular mechanisms that underlie TBI pathologies using the vast array of experimental tools and techniques available for flies.

Um Método para infligir Cabeça Fechada Lesão cerebral traumático em<em&gt; Drosophila</em

Traumatic brain injury (TBI) affects millions of people each year, causing impairment of physical, cognitive, and behavioral functions and death. Studies ...

Neurociência

Imaging Neural Activity in the Primary Somatosensory Cortex Using Thy1-GCaMP6s Transgenic Mice

The mammalian brain exhibits marked symmetry across the sagittal plane. However, detailed description of neural dynamics in symmetric brain regions in adult mammalian animals remains elusive. In this study, we describe an experimental procedure for measuring calcium dynamics through dual optical windows above bilateral primary somatosensory corticies (S1) in Thy1-GCaMP6s transgenic mice using 2-photon (2P) microscopy. This method enables recordings and quantifications of neural activity in bilateral mouse brain regions one at a time in the same experiment for a prolonged period in vivo. Key aspects of this method, which can be completed within an hour, include minimally invasive surgery procedures for creating dual optical windows, and the use of 2P imaging. Although we only demonstrate the technique in the S1 area, the method can be applied to other regions of the living brain facilitating the elucidation of structural and functional complexities of brain neural networks.

Imaging Neural Activity in the Primary Somatosensory Cortex Using Thy1-GCaMP6s Transgenic Mice

We describe an experimental procedure for measuring neuronal activity through dual optical windows above bilateral primary somatosensory corticies (S1) in Thy1-GCaMP6s transgenic mice using 2-photon (2P) microscopy in vivo.

Imagem de atividade Neural no córtex somatossensorial primário usando Thy1-GCaMP6s de ratos transgênicos

The mammalian brain exhibits marked symmetry across the sagittal plane. However, detailed description of neural dynamics in symmetric brain regions in ...

Automated Gait Analysis in Mice with Chronic Constriction Injury

The von Frey test is a classical method that has been widely used to examine the sensory function of neuropathic pain animals. However, it has some disadvantages such as subjective data and the requirement of a skilled, experienced experimenter. To date, a variety of modifications have improved the von Frey method, but it still has a few limitations. Recent reports have suggested that gait analysis produces more accurate and objective data from the neuropathic animals. This protocol demonstrates how to perform the automated gait analysis to determine the degree of neuropathic pain in mice. After several days of acclimation, the mice were allowed to walk freely on the glass floor to illuminate footprints. Then, quantification of the footprints and gait were performed through video clips with automatic analysis of various walking parameters, such as area of paw print, swing time, angle of paw, etc.
The main purpose of this study is to describe the methodology of automated gait analysis and briefly compare it with data from the classical sensory test using von Frey filament.

The precise assessment of pain response in a neuropathic animal model is critical to investigate the pathophysiology of pain diseases and develop new analgesics. We present a sensitive and objective method to determine the sensory function of the rodent hind paw by an automated gait analysis system.

Análise de marcha automatizados em ratos com lesão crônica de constrição

The von Frey test is a classical method that has been widely used to examine the sensory function of neuropathic pain animals. However, it has some ...

A Novel In Vitro Model of Blast Traumatic Brain Injury

Traumatic brain injury is a leading cause of death and disability in military and civilian populations. Blast traumatic brain injury results from the detonation of explosive devices, however, the mechanisms that underlie the brain damage resulting from blast overpressure exposure are not entirely understood and are believed to be unique to this type of brain injury. Preclinical models are crucial tools that contribute to better understand blast-induced brain injury. A novel in vitro blast TBI model was developed using an open-ended shock tube to simulate real-life open-field blast waves modelled by the Friedlander waveform. C57BL/6N mouse organotypic hippocampal slice cultures were exposed to single shock waves and the development of injury was characterized up to 72 h using propidium iodide, a well-established fluorescent marker of cell damage that only penetrates cells with compromised cellular membranes. Propidium iodide fluorescence was significantly higher in the slices exposed to a blast wave when compared with sham slices throughout the duration of the protocol. The brain tissue injury is very reproducible and proportional to the peak overpressure of the shock wave applied.

A Novel In Vitro Model of Blast Traumatic Brain Injury

This paper describes a novel model of primary blast traumatic brain injury. A compressed-air driven shock tube is used to expose in vitro mouse hippocampal slice cultures to a single shock wave. This is a simple and rapid protocol generating a reproducible brain tissue injury with a high throughput.

Um modelo de romance In Vitro de explosão traumatismo crânio-encefálico

Traumatic brain injury is a leading cause of death and disability in military and civilian populations. Blast traumatic brain injury results from the ...

Effects of Blast-induced Neurotrauma on Pressurized Rodent Middle Cerebral Arteries

Though there have been studies on the histopathological and behavioral effects of blast exposure, fewer have been dedicated to blast&#39;s cerebral vascular effects. Impact (i.e., non-blast) traumatic brain injury (TBI) is known to decrease pressure autoregulation in the cerebral vasculature in both humans and experimental animals. The hypothesis that blast-induced traumatic brain injury (bTBI), like impact TBI, results in impaired cerebral vascular reactivity was tested by measuring myogenic dilatory responses to reduced intravascular pressure in rodent middle cerebral arterial (MCA) segments from rats subjected to mild bTBI using an Advanced Blast Simulator (ABS) shock tube. Adult, male Sprague-Dawley rats were anesthetized, intubated, ventilated and prepared for Sham bTBI (identical manipulation and anesthesia except for blast injury) or mild bTBI. Rats were randomly assigned to receive Sham bTBI or mild bTBI followed by sacrifice 30 or 60 min post-injury. Immediately after bTBI, righting reflex (RR) suppression times were assessed, euthanasia at the time points post-injury was completed, the brain was harvested and the individual MCA segments were collected, mounted and pressurized. As the intraluminal pressure perfused through the arterial segments was reduced in 20 mmHg increments from 100 to 20 mmHg, MCA diameters were measured and recorded. With decreasing intraluminal pressure, MCA diameters steadily increased significantly above baseline in the Sham bTBI groups while MCA dilator responses were significantly reduced (p &#60; 0.05) in both bTBI groups as evidenced by the impaired, smaller MCA diameters recorded for the bTBI groups. In addition, RR suppression in the bTBI groups was significantly (p &#60; 0.05) higher than in the Sham bTBI groups. MCA&#39;s collected from the Sham bTBI groups exhibited typical vasodilatory properties to decreases in intraluminal pressure while MCA&#39;s collected following bTBI exhibited significantly impaired myogenic vasodilatory responses to reduced pressure that persisted for at least 60 min after bTBI.

Here, we present a protocol to describe methods for ex vivo vascular reactivity determination following a primary blast traumatic brain injury (bTBI) using isolated, pressurized, rodent middle cerebral arterial (MCA) segments. bTBI induction is accomplished using a shock tube, also known as an Advanced Blast Simulator (ABS) device.

Efeitos de Neurotrauma induzida por explosão em roedores pressurizado artérias cerebrais de médio

Though there have been studies on the histopathological and behavioral effects of blast exposure, fewer have been dedicated to blast&#39;s cerebral ...

Investigating Alterations in Caecum Microbiota After Traumatic Brain Injury in Mice

Increasing evidence shows that the microbiota-gut-brain axis plays an important role in the pathogenesis of brain diseases. Several studies also demonstrate that traumatic brain injuries cause changes to the gut microbiota. However, mechanisms underlying the bidirectional regulation of the brain-gut axis remain unknown. Currently, few models exist for studying the changes in gut microbiota after traumatic brain injury. Therefore, the presented study combines protocols for inducing traumatic brain injury using a lateral fluid percussion device and analysis of caecum samples following injury for investigating alterations in the gut microbiome. Alterations of the gut microbiota composition after traumatic brain injury are determined using 16S-rDNA sequencing. This protocol provides an effective method for studying the relationships between enteric microorganisms and traumatic brain injury.

Presented here is a protocol to induce diffuse traumatic brain injury using a lateral fluid percussion device followed by the collection of the caecum content for gut microbiome analysis.

Investigando alterações na microbiota de caecum após traumatismo cranioencefálico em camundongos

Increasing evidence shows that the microbiota-gut-brain axis plays an important role in the pathogenesis of brain diseases. Several studies also ...

Advanced Diffusion Imaging in The Hippocampus of Rats with Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) is the most common type of acquired brain injury. Since patients with traumatic brain injury show a tremendous variability and heterogeneity (age, gender, type of trauma, other possible pathologies, etc.), animal models play a key role in unraveling factors that are limitations in clinical research. They provide a standardized and controlled setting to investigate the biological mechanisms of injury and repair following TBI. However, not all animal models mimic the diffuse and subtle nature of mTBI effectively. For example, the commonly used controlled cortical impact (CCI) and lateral fluid percussion injury (LFPI) models make use of a craniotomy to expose the brain and induce widespread focal trauma, which are not commonly seen in mTBI. Therefore, these experimental models are not valid to mimic mTBI. Thus, an appropriate model should be used to investigate mTBI. The Marmarou weight drop model for rats induces similar microstructural alterations and cognitive impairments as seen in patients who sustain mild trauma; therefore, this model was selected for this protocol. Conventional computed tomography and magnetic resonance imaging (MRI) scans commonly show no damage following a mild injury, because mTBI induces often only subtle and diffuse injuries. With diffusion weighted MRI, it is possible to investigate microstructural properties of brain tissue, which can provide more insight into the microscopic alterations following mild trauma. Therefore, the goal of this study is to obtain quantitative information of a selected region-of-interest (i.e., hippocampus) to follow up disease progression after obtaining a mild and diffuse brain injury.

The overall goal of this procedure is to obtain quantitative microstructural information of the hippocampus in a rat with mild traumatic brain injury. This is done using an advanced diffusion-weighted magnetic resonance imaging protocol and region-of-interest based analysis of parametric diffusion maps.

Imagem latente avançada da difusão no Hippocampus dos ratos com ferimento de cérebro traumático suave

Mild traumatic brain injury (mTBI) is the most common type of acquired brain injury. Since patients with traumatic brain injury show a tremendous ...

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.

Modelo murino de impacto cortical controlado para a indução de traumatismo cranioencefálico

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

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.

Modelo de onda de explosão de baixa intensidade para avaliação pré-clínica de lesão cerebral traumática leve de cabeça fechada em roedores

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.

Modelo de Lesão Cerebral Traumática Leve em Camundongos com Controle Eletromagnético

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