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

Este trabajo fue apoyado por fondos de la Cord Indiana espinal y lesiones cerebrales Ayudas a la Investigación (SCBI 200-12), el Ralph W. y Grace Premio de Investigación Showalter M., Universidad de Indiana Investigaciones Biológicas Grant, NIH subvenciones RR025761 y 1R21NS072631-01A.

Cuidado de los Animales Masculino C57 BL / 6 ratones fueron alojados en grupos y se mantuvieron en un 12/12 horas de luz / oscuridad ciclo con el libre acceso al alimento y agua ad libitum. Los animales utilizados en este protocolo fueron 10-12 semanas de edad. Todos los procedimientos se realizaron bajo los protocolos aprobados por el Comité de Cuidado de Animales y el empleo de la Universidad de Indiana. 1. Preparación quirúrgica <ol><li> Se anestesia el ratón utilizando una mezcla de ketamina / xilazina (87,7 mg / ml de ketamina y 12,3 mg / ml de xilazina) y administrar (1 ml / kg) a través de inyección IP. </li><li> Afeitarse la cabeza del ratón entre las orejas. </li><li> Aplicar una gelatina a base de petróleo a los ojos del ratón para evitar que se sequen durante la cirugía. </li><li> Limpie la zona afeitada con un 10% de yodo. A continuación, utilice etanol al 70% para limpiar el yodo. </li><li> Fijar la cabeza del ratón en el marco estereotáctico utilizando las barras de oído y placa de mordida. Asegúrese de que el cerebro es estable. </li></ol> 2. Craniectomía </p&gt; <ol><li> Hacer una incisión longitudinal en el centro de la cabeza con unas tijeras. Use una pinza hemostática para mantener la piel en el lateral izquierdo. </li><li> Utilice un aplicador con punta de algodón para quitar la sangre y el tejido del hueso para exponer el cráneo. Permitir cráneo expuesto se seque durante 1 min. </li><li> El uso de fórceps para ejercer presión y asegurarse de que el cráneo permanece inmóvil. Identificar puntos de referencia anatómicos Lambda (aspecto caudal) y Bregma (aspecto frontal). Dibuje un círculo en el centro de Lambda y Bregma con un diámetro de 4 mm y 0,5 mm de la línea media. </li><li> Use un taladro para cortar a lo largo del círculo marcado. Sople suavemente el polvo de huesos de distancia. No perfore completamente a través del hueso para evitar que se dañe la duramadre. </li><li> El uso de fórceps para quitar el hueso y exponer la duramadre. </li></ol> 3. Impactación El sistema de impacto incluye una caja de control para establecer los parámetros de impacto, un dispositivo de accionamiento para realizar la impactación, y un marco estereotáctico para garantizar el actouator y la cabeza de ratón para el impacto. <ol><li> Pre-establecer la velocidad del actuador a 3 m / seg antes de la cirugía. </li><li> Pre-set diferente profundidad de deformación para inducir diferentes niveles de gravedad de lesiones. Profundidades de deformación de 0,0 a 0,2 mm, 0,5 a 1,0 mm, y 1,2 a 2,0 mm resultaría en lesiones cerebrales traumáticas leves, moderados y graves, respectivamente. Este protocolo explica cómo lograr una lesión cerebral moderadamente grave con una profundidad de deformación de 1 mm mediante el uso de una velocidad de 3 m / seg. </li><li> Fije el actuador a la titular en el marco estereotáctico y utilizar los micromanipuladores moviéndolo para asegurar la punta redonda y plana del actuador (3 mm de diámetro) en el centro de la zona cráneo abierto. A continuación, ajuste la punta en un ángulo paralelo a la superficie del lugar del impacto. </li><li> Establecer el punto cero moviendo hacia abajo el actuador en el modelo que se extiende hasta la punta toque la superficie del lugar del impacto. A continuación, establezca el canal Z en el panel de control estereotáctica a cero. </li><li> Retirar la punta impactadormientras se mueve simultáneamente el actuador hacia abajo 1 mm. </li><li> Pulse el botón de impacto para golpear el sitio de la lesión y lograr una profundidad de deformación de 1 mm. </li></ol> 4. Lesión del sitio de cierre <ol><li> Utilice bastoncillos de algodón para eliminar cualquier impacto sangre después, pero no toque la zona de la lesión. </li><li> Coloque el ratón sobre una almohadilla caliente para mantener la temperatura corporal. </li><li> Una vez que el sangrado se haya detenido, suturar la herida cerrada. Ponga el animal dentro de la jaula limpia y deje que se recupere de la cirugía durante la noche en la almohadilla caliente. </li><li> Administrar Buprenorfina 0,05-0,10 mg / kg vía subcutánea cada 8 a 12 horas durante 2 días después de la cirugía. </li></ol>

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The authors have nothing to disclose.

Los pasos más importantes para la generación de éxito LCT consistentes utilizando un sistema de impacto imán electrónico para causar una CCI son: 1) la fijación estable de la cabeza del ratón en el marco estereotáctico; 2) generar el mismo tamaño de ventana de hueso entre los ratones y eliminar el hueso sin dañar la duramadre debajo de ella durante la craniectomía; 3) colocar correctamente la punta del impacto en el centro de la zona abierta y establecer el punto cero antes de impactar. <p class="jove_con...

La lesión cerebral traumática (TBI) se define como una alteración de la función cerebral, u otra evidencia de patología cerebral, causada por una fuerza externa 1. LCT siguen siendo un grave problema de salud en todo el mundo, particularmente en los Estados Unidos. Según los Centros para el Control y la Prevención de Enfermedades, por lo menos 1.7 millones de lesiones cerebrales traumáticas se producen anualmente en los Estados Unidos lo que resulta en un 30,5% de todas las muertes relacionadas con lesiones. En 2000, los costos médicos directos y los costos indirectos de la LCT totalizaron un estimado de 76,5 mil millones dólares en los Estados Unidos solamente. Aunque los avances tecnológicos y terapéuticos en décadas anteriores se ha mejorado la calidad y la duración de vida de aquellos que sufren de lesiones cerebrales traumáticas, actualmente no existen farmacéutica eficaz o tratamientos preventivos. Debido a la complejidad y efectos de gran alcance de la LCT, incluyendo lesiones de los tejidos, la muerte celular y la degeneración axonal, no hay dos lesiones son idénticos; por lo tanto, no hay un modelo de TBI de corriente para animales reproduce con precisióntodos los aspectos de TBI como se ve en los seres humanos. Sin embargo, los modelos animales proporcionan la capacidad de producir lesiones casi idénticos necesarias para investigar diversos efectos de TBI con la esperanza de una mayor comprensión de las manifestaciones clínicas de la LCT. El modelo controlado impacto cortical (CCI) utiliza un sistema de impacto para entregar impacto físico a la duramadre expuesta de un animal. Induce LCT que van de leves a graves similares a los experimentados por los seres humanos. Esta lesión se caracteriza por primera vez en el hurón 2 y fue adaptado más adelante para su uso en la rata 3,4, ratón 5-7, y ovejas 8. Desde la primera caracterización, el sitio de la lesión se ha colocado tanto sobre la línea media de 2,9 y la corteza lateral 10. CCI ofrece un método fácil y preciso de la investigación de los efectos y posibles tratamientos para lesiones cerebrales traumáticas. Además del modelo de CCI, la percusión de fluido y caída de peso modelos son commonly utilizado para producir lesiones cerebrales traumáticas. Sin embargo, estos modelos ofrecen limitaciones, entre ellas un menor control sobre los parámetros de lesión, produciendo cambios histopathalogical no vistos en LCT humano y mayor incidencia de muerte accidental en ratones 3,5,10. El modelo de onda expansiva también se utiliza para producir lesiones cerebrales traumáticas. Aunque el modelo de onda expansiva no reproduce los cambios histopathalogical visto después de un impacto mecánico, este modelo no producir con precisión lesiones cerebrales traumáticas experimentadas en particular por el personal militar 11. El modelo de impacto cortical controlado es fácil de controlar debido al control preciso sobre los parámetros de deformación, tales como el tiempo, la velocidad y la profundidad de impacto 5. Tal precisión hace que la replicación de lesiones casi idénticos a través de todo un grupo de animales más factibles. Lo más importante, CCI reproduce LCT con características que se observan en la LCT humana 12. Sin embargo, no hay ningún modelo animal único que es del todo satisfactoria en la reproducción del espectro completo de patológica Chanbios observados después de TBI. Se necesita más investigación para revelar plenamente los cambios agudos y crónicos que se producen después de TBI. Hay dos tipos de lesiones se producen después de una lesión cerebral traumática: lesiones primarias y secundarias. La lesión primaria se produce en el momento del impacto y no es sensible a tratamientos terapéuticos; Sin embargo, las lesiones secundarias que persisten después de la lesión inicial están sujetos a los tratamientos 13. El modelo de impacto cortical controlado produce la lesión primaria, lo que permite a los investigadores estudiar los efectos de la lesión cerebral traumática y tratamientos terapéuticos potenciales para los efectos potencialmente de larga duración de las lesiones secundarias. Áreas de potencial de investigación utilizando el modelo CCI incluyen la muerte neuronal, edema cerebral, la neurogénesis, efectos vasculares, cambios histopathalogical y déficits de memoria y más 3,13-16.

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controlled cortical impact model for traumatic brain injury

Every year over a million Americans suffer a traumatic brain injury (TBI). Combined with the incidence of TBIs worldwide, the physical, emotional, social, and economical effects are staggering. Therefore, further research into the effects of TBI and effective treatments is necessary. The controlled cortical impact (CCI) model induces traumatic brain injuries ranging from mild to severe. This method uses a rigid impactor to deliver mechanical energy to an intact dura exposed following a craniectomy. Impact is made under precise parameters at a set velocity to achieve a pre-determined deformation depth. Although other TBI models, such as weight drop and fluid percussion, exist, CCI is more accurate, easier to control, and most importantly, produces traumatic brain injuries similar to those seen in humans. However, no TBI model is currently able to reproduce pathological changes identical to those seen in human patients. The CCI model allows investigation into the short-term and long-term effects of TBI, such as neuronal death, memory deficits, and cerebral edema, as well as potential therapeutic treatments for TBI.

El modelo de impacto cortical controlado produce lesiones cerebrales traumáticas que varían en gravedad de leve a grave. Post-impacto la cantidad de inflamación craneal, hemorragia, y la distorsión del cráneo en el sitio de impacto revelan la gravedad de las lesiones resultantes de los parámetros de velocidad y profundidad de la deformación. LCT leve como resultado hinchazón craneal en el lugar del impacto y sangrado leve como consecuencia del incumplimiento duración limitada. A TCE moderado presenta hinchazón...

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.

Controlado Modelo de Impacto cortical de la lesión cerebral traumática

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 vistas.  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.

Modelo de impacto cortical controlado de lesión cerebral de ratón con trasplante terapéutico de células neuronales derivadas de células madre pluripotentes inducidas por el hombre

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

Investigación

Biología del Desarrollo

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 modelo de lesión en la cabeza repetidos de conmoción en ratones

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 Modelo de Ratón de Único y Repetitivo Lesión Cerebral Traumática Leve

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.

Modelo Murino de Impacto Cortical Controlado para la Inducción de Lesiones Cerebrales Traumáticas

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

Neurociencias

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 blástica de baja intensidad para la evaluación preclínica de la lesión cerebral traumática leve de cabeza cerrada en 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 ...

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 modelo preclínico de impacto cortical controlado para hemorragia traumática, contusión y neuroinflamación

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 modelo preclínico de impacto cortical controlado para hemorragia traumática, contusión y neuroinflamación

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.

Modelo electromagnético controlado de cabeza cerrada de lesión cerebral traumática leve en ratones

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.

Evaluación de los cambios en la plasticidad sináptica utilizando un modelo de lesión cerebral traumática leve con vigilia

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

Inducción de rmTBI en ratones a través de un método de lesión de cabeza cerrada

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

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

Autor destacado: Optimización de modelos de roedores para investigar los mecanismos y la rehabilitación en lesiones cerebrales traumáticas leves repetidas

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.

Modelo de ratón modificado de lesión cerebral traumática leve repetitiva que incorpora ventana de cráneo adelgazada y percusión de fluidos

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

Controlado Modelo de Impacto cortical de la lesión cerebral traumática

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