Este trabajo fue apoyado por R01 NS067417 del Instituto Nacional de Trastornos Neurológicos y derrame cerebral (MPB).

Estos estudios se realizaron en estricta conformidad con las recomendaciones de la Guía para el Cuidado y Uso de Animales de Laboratorio de los Institutos Nacionales de Salud. El protocolo fue aprobado por el Comité Institucional de Cuidado y Uso de Animales en la Universidad de Georgetown. Los ratones se alojaron en una instalación de animales controlados por temperatura y se mantuvieron en un ciclo de 12 h de luz / 12 h de oscuridad. Alimentos y agua estaban disponibles ad libitum . 1. Preparación del aparato mTBI NOTA: El aparato mTBI incluye una caja de adquisición de datos (DAQ) para controlar los parámetros de impacto, un impactador neumático de alta velocidad para realizar la impactación y una base llena de gel moldeada para desacelerar la cabeza después del impacto. <ol><li> Encienda el aire comprimido e inicie el impactador neumático de alta velocidad a una presión de 861,85 kPa. </li><li> Calibre el sistema de control DAQ a los siguientes parámetros: velocidad del pistón de 2,35 m / s,E de 31,5 ms. </li><li> Coloque la base moldeada rellena de gel (compresibilidad 64 kPa / mm) de manera que la línea media sea perpendicular con la trayectoria de la punta del impactador. </li></ol> 2. Impacto de mTBI <ol><li> Registre los pesos de todos los ratones que se van a usar. </li><li> Anestesiar ratones con isoflurano al 3% en oxígeno durante 120 s en una cámara de inducción. </li><li> Transferencia de ratones a mTBI aparato, continuación de la anestesia a través de una flexible, no fijo cono de la nariz. </li><li> Mientras que en el cono de la nariz, coloque la cabeza del ratón sobre la almohadilla de gel para que la superficie plana del cráneo se presenta perpendicular a la punta del impactador. </li><li> Coloque la cinta sobre la cabeza del ratón para crear una superficie plana y mantener las orejas lejos del sitio de impacto. </li><li> Baje la punta del impactador de politetrafluoroetileno para alinearla con la línea media sagital en el centro de la cabeza. La punta del impactador utilizada es de 10 mm de diámetro y cubrirá el área del cuero cabelludo desde justo detrás de los ojos hasta la línea media de las orejas. Ajuste el impactador para que sea juSt tocando la superficie de la cabeza del ratón. </li><li> Retirar la punta del impactador y marcar manualmente la profundidad de deflexión requerida (7,5 mm). </li><li> Arme el sistema de control DAQ y presione el botón de disparo para impactar la cabeza del ratón, ya sea un impacto singular o repetitivo. Los impactos repetitivos se producen en sucesión sin demora entre cada impacto. </li><li> Inmediatamente después del impacto final, eliminar el ratón de la anestesia y el aparato mTBI y colocar en posición supina. </li><li> El uso de un cronómetro mide la latencia del retorno del reflejo de enderezamiento (supino a propenso), para determinar la pérdida de tiempo de la conciencia, así como el tiempo para la deambulación (caminar sin obstáculos). </li><li> Monitor de ratón y en la recuperación a un comportamiento normal, volver a su jaula de origen. </li><li> Los ratones Sham reciben manipulación idéntica y anestesia, pero no reciben ningún impacto. </li></ol>

<ol>
	<li>McMahon, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Symptomatology+and+functional+outcome+in+mild+traumatic+brain+injury:+results+from+the+prospective+TRACK-TBI+study.">Symptomatology and functional outcome in mild traumatic brain injury: results from the prospective TRACK-TBI study.</a> J Neurotrauma. 31 (1), 26-33 (2014).</li><li>Barkhoudarian, G., Hovda, D. A., Giza, C. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+molecular+pathophysiology+of+concussive+brain+injury.">The molecular pathophysiology of concussive brain injury.</a> Clin Sports Med. 30 (1), 33-48 (2011).</li><li>Blennow, K., Hardy, J., Zetterberg, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+neuropathology+and+neurobiology+of+traumatic+brain+injury.">The neuropathology and neurobiology of traumatic brain injury.</a> Neuron. 76 (5), 886-899 (2012).</li><li>Levin, H. S., Diaz-Arrastia, R. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnosis,+prognosis,+and+clinical+management+of+mild+traumatic+brain+injury.">Diagnosis, prognosis, and clinical management of mild traumatic brain injury.</a> Lancet Neurol. 14 (5), 506-517 (2015).</li><li>McCrory, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Consensus+statement+on+concussion+in+sport:+the+4th+International+Conference+on+Concussion+in+Sport,+Zurich,+November+2012.">Consensus statement on concussion in sport: the 4th International Conference on Concussion in Sport, Zurich, November 2012.</a> J Athl Train. 48 (4), 554-575 (2012).</li><li>Talavage, T. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functionally-detected+cognitive+impairment+in+high+school+football+players+without+clinically-diagnosed+concussion.">Functionally-detected cognitive impairment in high school football players without clinically-diagnosed concussion.</a> J Neurotrauma. 31 (4), 327-338 (2014).</li><li>Angoa-Perez, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+of+sports-related+head+injury:+bridging+the+gap+between+pre-clinical+research+and+clinical+reality.">Animal models of sports-related head injury: bridging the gap between pre-clinical research and clinical reality.</a> J Neurochem. 129 (6), 916-931 (2014).</li><li>Creed, J. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Concussive+brain+trauma+in+the+mouse+results+in+acute+cognitive+deficits+and+sustained+impairment+of+axonal+function.">Concussive brain trauma in the mouse results in acute cognitive deficits and sustained impairment of axonal function.</a> J Neurotrauma. 28 (4), 547-563 (2011).</li><li>Hamberger, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Concussion+in+professional+football:+morphology+of+brain+injuries+in+the+NFL+concussion+model--part+16.">Concussion in professional football: morphology of brain injuries in the NFL concussion model--part 16.</a> Neurosurgery. 64 (6), 1174-1182 (2009).</li><li>Kane, M. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+mouse+model+of+human+repetitive+mild+traumatic+brain+injury.">A mouse model of human repetitive mild traumatic brain injury.</a> J Neurosci Methods. 203 (1), 41-49 (2012).</li><li>Prins, M. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Repeat+traumatic+brain+injury+in+the+juvenile+rat+is+associated+with+increased+axonal+injury+and+cognitive+impairments.">Repeat traumatic brain injury in the juvenile rat is associated with increased axonal injury and cognitive impairments.</a> Dev Neurosci. 32 (5-6), 510-518 (2010).</li><li>Tang, Y. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+concussive-like+brain+injury+model+in+mice+(II):+selective+neuronal+loss+in+the+cortex+and+hippocampus.">A concussive-like brain injury model in mice (II): selective neuronal loss in the cortex and hippocampus.</a> J Neurotrauma. 14 (11), 863-873 (1997).</li><li>Winston, C. N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dendritic+Spine+Loss+and+Chronic+White+Matter+Inflammation+in+a+Mouse+Model+of+Highly+Repetitive+Head+Trauma.">Dendritic Spine Loss and Chronic White Matter Inflammation in a Mouse Model of Highly Repetitive Head Trauma.</a> Am J Pathol. 186 (3), 552-567 (2016).</li><li>Johnson, V. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inflammation+and+white+matter+degeneration+persist+for+years+after+a+single+traumatic+brain+injury.">Inflammation and white matter degeneration persist for years after a single traumatic brain injury.</a> Brain. 136, 28-42 (2013).</li><li>Barrio, J. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+characterization+of+chronic+traumatic+encephalopathy+using+[F-18]FDDNP+PET+brain+imaging.">In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging.</a> Proc Natl Acad Sci U S A. 112 (16), 2039-2047 (2015).</li></ol>

Los autores no tienen nada que revelar.

En los seres humanos, mTBI se caracteriza por un deterioro funcional en ausencia de lesión estructural. Esto puede ocurrir con, o sin, una pérdida de conciencia 1 . Actualmente se piensa que la exposición a conmociones cerebrales repetidas es la base del desarrollo y / o progresión de enfermedades neurodegenerativas tales como CTE 4 . Está bien documentado que CTE se encuentra comúnmente en los boxeadores y jugadores de fútbol y aunque la exposición a la repetició...

Lesión cerebral traumática (TBI) se define como una lesión en la cabeza sostenida de una fuerza física externa, lo que resulta en la interrupción de la función cerebral normal. Representa una importante carga socioeconómica y de salud pública, y el Centro para el Control y la Prevención de Enfermedades Informe 2015 al Congreso estima que 2,5 millones de estadounidenses sufren un TBI cada año. Esto afecta no sólo la calidad de vida del paciente, sino que también coloca un costo económico extremadamente alto en la comunidad, estimado actualmente en 76.500 millones de dólares anuales. La cantidad de daño cerebral real transmitida y las sintomatologías de fase aguda es lo que define la lesión cerebral leve, moderada y grave. Lesión cerebral traumática leve (mTBI), también conocida como conmoción cerebral, representa más del 70% de los TBI reportados cada año 1 . Es más común entre los atletas que participan en deportes de contacto de alto riesgo incluyendo el boxeo y el fútbol 2 . A diferencia de lo moderadoO formas graves de TBI, el daño inmediato y los síntomas asociados con mTBI a veces no son tan pronunciados 3 . Por el contrario, los efectos a largo plazo de mTBI pueden ser tan debilitantes como los observados en las formas moderada y severa. Aquellos que sufren de mTBI repetitivo han demostrado desarrollar encefalopatía traumática crónica (CTE), así como otras enfermedades cognitivas y degenerativas [ 4] . Por lo tanto, es importante obtener una mayor comprensión de los mecanismos que contribuyen a los síntomas a corto plazo y el daño general a largo plazo que surge después de mTBI. En los seres humanos, la definición de conmoción cerebral definida por la Cuarta Conferencia Internacional sobre Conmoción cerebral en el Deporte (Zurich 2012) 5 establece que el nivel de lesión en la conmoción deportiva es leve, no causa cambios patológicos graves, pero causa déficits neurológicos a corto plazo Que se resuelven espontáneamente. De hecho, un receNt estudio investigó el efecto de mTBI en el deterioro cognitivo en los jugadores de fútbol de la escuela secundaria, utilizando los sistemas de telemetría de impacto de la cabeza. Este estudio mostró la cantidad de veces que los jugadores sufrieron impactos de casco&gt; 20 g en una sola temporada oscilando entre un mínimo de 226 (media, 4,7 por sesión) a un máximo de 1855 (promedio, 38,6 por sesión) 6 . La mayoría de estos impactos no resultaron en el diagnóstico clínico de una conmoción cerebral; Pero la evidencia de los cambios funcionales en la función cerebral se pudo observar utilizando fMRI [ 6] . Los cambios cerebrales que causan estos cambios funcionales son desconocidos, y por lo tanto hay una necesidad apremiante de tener un modelo fiable y reproducible para facilitar la investigación en los efectos de la mTBI concussive y subconcussive. A pesar de los intentos anteriores de modelar mTBI en ratones y ratas 7 , muchos reportan efectos adversos. En particular, la mayoría de los modelos de roedores están limitados en su naturaleza repetitiva,Un cinco impactos mTBI, así como tener eventos patológicos adversos, incluyendo sangrado intracerebral, fracturas del cráneo, lesiones axonales graves, muerte de células neuronales, y el aumento de la mortalidad 8 , 9 , 10 , 11 , 12 . En este documento, describimos un modelo de ratón de mTBI que está más cerca de la verdadera definición de conmoción cerebral en los seres humanos. Este modelo recapitula muchos de los síntomas observados en el mTBI humano, tales como la fuerza mecánica que resulta en la pérdida transitoria de conciencia sin patología cerebral cruda manifiesta. Además, es ventajoso en el hecho de que puede ser utilizado tanto para el impacto único y los paradigmas de impacto repetitivo durante largos períodos de tiempo como se informó anteriormente [ 13] .

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a mouse model of single and repetitive mild traumatic brain injury

La lesión cerebral traumática leve (mTBI) puede resultar en la pérdida aguda de la función cerebral, incluyendo un período de confusión, pérdida de conciencia (LOC), déficits neurológicos focales e incluso amnesia. Los atletas que participan en deportes de contacto tienen un alto riesgo de exposición a un gran número de mTBI. En términos de nivel de lesión en un atleta deportivo, un mTBI se define como una lesión leve que no causa grandes cambios patológicos, pero sí causa deficiencias neurológicas a corto plazo que se resuelven espontáneamente. A pesar de los intentos anteriores de modelar mTBI en ratones y ratas, muchos han reportado efectos adversos graves incluyendo fracturas de cráneo, hemorragia intracerebral, lesión axonal y muerte celular neuronal. En este documento, describimos nuestro altamente reproducible modelo animal de mTBI que reproduce síntomas clínicamente relevantes. Este modelo utiliza un dispositivo de impactador neumático a medida para producir un traumatismo de cabeza cerrada. Este impacto se realiza bajo parámetros precisos de velocidad y deformación,Creando un modelo confiable y reproducible para examinar los mecanismos que contribuyen a los efectos de la mTBI concussiva única o repetitiva.

El uso de este nuevo dispositivo mTBI permite las lesiones simples y repetitivas en la cabeza sin riesgo de fractura craneal o daño cerebral estructural. El modelo utiliza un dispositivo de impacto personalizado de neumático Teflon para entregar un impacto de energía mecánica de cabeza cerrada. El impacto se realiza bajo parámetros precisos de velocidad y deformación, creando un modelo fiable y reproducible para examinar los mecanismos que contribuyen a los efectos del mTBI concuss...

Watch this Scientific Journal Video about A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury at JoVE.com

A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury

Los atletas absorben varios cientos de lesiones cerebrales traumáticas leves (mTBI) / concusiones cada año; Sin embargo, la consecuencia de éstos en el cerebro es mal entendida. Por lo tanto, un modelo animal de mTBI único y repetitivo que repeticiones consistentes clínicamente relevantes síntomas proporciona los medios para avanzar en el estudio de mTBI y concusión.

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 ...

a-mouse-model-of-single-and-repetitive-mild-traumatic-brain-injury

Research

JoVE Journal

Medicine

11.0K vistas.  Georgetown University Medical Center.  Los atletas absorben varios cientos de lesiones cerebrales traumáticas leves (mTBI) / concusiones cada año; Sin embargo, la consecuencia de éstos en el cerebro es mal entendida. Por lo tanto, un modelo animal de mTBI único y repetitivo que repeticiones consistentes clínicamente relevantes síntomas proporciona los medios para avanzar en el estudio de mTBI y concusión. 

Video: A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury

Normothermic Cardiac Arrest and Cardiopulmonary Resuscitation: A Mouse Model of Ischemia-Reperfusion Injury

Acute Kidney Injury (AKI) is a common, highly lethal, complication of critical illness which has a high mortality1-4 and which is most 
frequently caused by whole-body hypoperfusion.5,6 Successful reproduction of whole-body hypoperfusion in rodent models has been fraught with 
difficulty.7-9,9,10 Models which employ focal ischemia have repeatedly demonstrated results which do not translate to the clinical setting, and larger 
animal models which allow for whole body hypoperfusion lack access to the full toolset of genetic manipulation possible in the mouse.11,12 However, in recent 
years a mouse model of cardiac arrest and cardiopulmonary resuscitation has emerged which can be adapted to model AKI.13 This model reliably reproduces 
physiologic, functional, anatomic, and histologic outcomes seen in clinical AKI, is rapidly repeatable, and offers all of the significant advantages of a murine surgical 
model, including access to genetic manipulative techniques, low cost relative to large animals, and ease of use. Our group has developed extensive experience 
with use of this model to assess a number of organ-specific outcomes in AKI.14,15

A powerful model for perioperative and critical care related acute kidney injury is presented. Using whole body hypoperfusion induced by cardiac arrest it is possible to nearly replicate the histologic and functional changes of clinical AKI.

Arresto normotérmica cardiaca y reanimación cardiopulmonar: un modelo de ratón de la lesión por isquemia-reperfusión

Acute Kidney Injury (AKI) is a common, highly lethal, complication of critical illness which has a high mortality1-4 and which is most 
frequently caused ...

Investigación

Medicina

Biomarkers in an Animal Model for Revealing Neural, Hematologic, and Behavioral Correlates of PTSD

Identification of biomarkers representing the evolution of the pathophysiology of Post Traumatic Stress Disorder (PTSD) is vitally important, not only for objective diagnosis but also for the evaluation of therapeutic efficacy and resilience to trauma. Ongoing research is directed at identifying molecular biomarkers for PTSD, including traumatic stress induced proteins, transcriptomes, genomic variances and genetic modulators, using biologic samples from subjects' blood, saliva, urine, and postmortem brain tissues. However, the correlation of these biomarker molecules in peripheral or postmortem samples to altered brain functions associated with psychiatric symptoms in PTSD remains unresolved. Here, we present an animal model of PTSD in which both peripheral blood and central brain biomarkers, as well as behavioral phenotype, can be collected and measured, thus providing the needed correlation of the central biomarkers of PTSD, which are mechanistic and pathognomonic but cannot be collected from people, with the peripheral biomarkers and behavioral phenotypes, which can.
Our animal model of PTSD employs restraint and tail shocks repeated for three continuous days - the inescapable tail-shock model (ITS) in rats. This ITS model mimics the pathophysiology of PTSD 17, 7, 4, 10. We and others have verified that the ITS model induces behavioral and neurobiological alterations similar to those found in PTSD subjects 17, 7, 10, 9. Specifically, these stressed rats exhibit (1) a delayed and exaggerated startle response appearing several days after stressor cessation, which given the compressed time scale of the rat's life compared to a humans, corresponds to the one to three months delay of symptoms in PTSD patients (DSM-IV-TR PTSD Criterian D/E 13), (2) enhanced plasma corticosterone (CORT) for several days, indicating compromise of the hypothalamopituitary axis (HPA), and (3) retarded body weight gain after stressor cessation, indicating dysfunction of metabolic regulation.
The experimental paradigms employed for this model are: (1) a learned helplessness paradigm in the rat assayed by measurement of acoustic startle response (ASR) and a charting of body mass; (2) microdissection of the rat brain into regions and nuclei; (3) enzyme-linked immunosorbent assay (ELISA) for blood levels of CORT; (4) a gene expression microarray plus related bioinformatics tools 18. This microarray, dubbed rMNChip, focuses on mitochondrial and mitochondria-related nuclear genes in the rat so as to specifically address the neuronal bioenergetics hypothesized to be involved in PTSD.

We describe a rat model of post traumatic stress disorder (PTSD) that reveals the persistent alterations in neuroendocrine function and the delayed long-term, exaggerated fear response, characteristic of PTSD patients. The animal model and methods described here are useful for correlating biomarkers in brain nuclei, which are mechanistic but cannot be measured in patients, with biomarkers in peripheral white blood cells, which can.

Biomarcadores en un modelo animal para Revelar correlatos neurales, hematológicas y conductuales de estrés postraumático

Identification of biomarkers representing the evolution of the pathophysiology of Post Traumatic Stress Disorder (PTSD) is vitally important, not only for ...

Stretch in Brain Microvascular Endothelial Cells (cEND) as an In Vitro Traumatic Brain Injury Model of the Blood Brain Barrier

Due to the high mortality incident brought about by traumatic brain injury (TBI), methods that would enable one to better understand the underlying mechanisms involved in it are useful for treatment. There are both in vivo and in vitro methods available for this purpose. In vivo models can mimic actual head injury as it occurs during TBI. However, in vivo techniques may not be exploited for studies at the cell physiology level. Hence, in vitro methods are more advantageous for this purpose since they provide easier access to the cells and the extracellular environment for manipulation.
Our protocol presents an in vitro model of TBI using stretch injury in brain microvascular endothelial cells. It utilizes pressure applied to the cells cultured in flexible-bottomed wells. The pressure applied may easily be controlled and can produce injury that ranges from low to severe. The murine brain microvascular endothelial cells (cEND) generated in our laboratory is a well-suited model for the blood brain barrier (BBB) thus providing an advantage to other systems that employ a similar technique. In addition, due to the simplicity of the method, experimental set-ups are easily duplicated. Thus, this model can be used in studying the cellular and molecular mechanisms involved in TBI at the BBB.

Stretch in Brain Microvascular Endothelial Cells cEND as an In Vitro Traumatic Brain Injury Model of the Blood Brain Barrier

In vitro traumatic brain injury models are being developed to reproduce in vivo brain deformation. Stretch-induced injury has been employed for astrocytes, neurons, glial cells, aortic, and brain endothelial cells. However, our system uses a blood brain barrier (BBB) model that possesses properties constituting a legitimate model of the BBB to establish an in vitro&#160;TBI model.

Estirar en Brain células endoteliales microvasculares (CEND) como<em&gt; In Vitro</em&gt; Lesión cerebral traumática Modelo de la barrera hematoencefálica

Due to the high mortality incident brought about by traumatic brain injury (TBI), methods that would enable one to better understand the underlying ...

An Alkali-burn Injury Model of Corneal Neovascularization in the Mouse

Under normal conditions, the cornea is avascular, and this transparency is essential for maintaining good visual acuity. Neovascularization (NV) of the cornea, which can be caused by trauma, keratoplasty or infectious disease, breaks down the so called &lsquo;angiogenic privilege' of the cornea and forms the basis of multiple visual pathologies that may even lead to blindness. Although there are several treatment options available, the fundamental medical need presented by corneal neovascular pathologies remains unmet. In order to develop safe, effective, and targeted therapies, a reliable model of corneal NV and pharmacological intervention is required. Here, we describe an alkali-burn injury corneal neovascularization model in the mouse. This protocol provides a method for the application of a controlled alkali-burn injury to the cornea, administration of a pharmacological compound of interest, and visualization of the result. This method could prove instrumental for studying the mechanisms and opportunities for intervention in corneal NV and other neovascular disorders.

Neovascularization (NV) of the cornea can complicate multiple visual pathologies. Utilizing a controlled, alkali-burn injury model, a quantifiable level of corneal NV can be produced for mechanistic study of corneal NV and evaluation of potential therapies for neovascular disorders.

Una Lesión álcalis quemar modelo de neovascularización corneal en el ratón

Under normal conditions, the cornea is avascular, and this transparency is essential for maintaining good visual acuity. Neovascularization (NV) of the ...

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.

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, ...

Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration

Renal ischaemia reperfusion injury (IRI) is a common cause of acute kidney injury (AKI) in patients and occlusion of renal blood flow is unavoidable during renal transplantation. Experimental models that accurately and reproducibly recapitulate renal IRI are crucial in dissecting the pathophysiology of AKI and the development of novel therapeutic agents. Presented here is a mouse model of renal IRI that results in reproducible AKI. This is achieved by a midline laparotomy approach for the surgery with one incision allowing both a right nephrectomy that provides control tissue and clamping of the left renal pedicle to induce ischaemia of the left kidney. By careful monitoring of the clamp position and body temperature during the period of ischaemia this model achieves reproducible functional and structural injury. Mice sacrificed 24 hr&#160;following surgery demonstrate loss of renal function with elevation of the serum or plasma creatinine level as well as structural kidney damage with acute tubular necrosis evident. Renal function improves and the acute tissue injury resolves during the course of 7 days following renal IRI such that this model may be used to study renal regeneration. This model of renal IRI has been utilized to study the molecular and cellular pathophysiology of AKI as well as analysis of the subsequent renal regeneration.

The mouse model of renal ischaemia reperfusion injury described here comprises of a right nephrectomy that provides control tissue and clamping of the left renal pedicle to induce ischaemia that results in acute kidney injury. This model uses a midline laparotomy approach with all steps performed via one incision.

La isquemia reperfusión renal: un modelo de ratón de la lesión y regeneración

Renal ischaemia reperfusion injury (IRI) is a common cause of acute kidney injury (AKI) in patients and occlusion of renal blood flow is unavoidable ...

A Novel Model of Mild Traumatic Brain Injury for Juvenile Rats

Despite growing evidence that childhood represents a major risk period for mild traumatic brain injury (mTBI) from sports-related concussions, motor vehicle accidents, and falls, a reliable animal model of mTBI had previously not been developed for this important aspect of development. The modified weight-drop technique employs a glancing impact to the head of a freely moving rodent transmitting acceleration, deceleration, and rotational forces upon the brain. When applied to juvenile rats, this modified weight-drop technique induced clinically relevant behavioural outcomes that were representative of post-concussion symptomology. The technique is a rapidly applied procedure with an extremely low mortality rate, rendering it ideal for high-throughput studies of therapeutics. In addition, because the procedure involves a mild injury to a closed head, it can easily be used for studies of repetitive brain injury. Owing to the simplistic nature of this technique, and the clinically relevant biomechanics of the injury pathophysiology, the modified weight-drop technique provides researchers with a reliable model of mTBI that can be used in a wide variety of behavioural, molecular, and genetic studies.

The modified weight-drop technique is an easy, cost-effective procedure used for the induction of mild traumatic brain injury in juvenile rats. This novel technique produces clinically relevant symptomology that will advance the study of mild traumatic brain injury (mTBI) and concussion.

Un nuevo modelo de leve lesión cerebral traumática para ratas jóvenes

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

A Neonatal Mouse Spinal Cord Compression Injury Model

Spinal cord injury (SCI) typically causes devastating neurological deficits, particularly through damage to fibers descending from the brain to the spinal cord. A major current area of research is focused on the mechanisms of adaptive plasticity that underlie spontaneous or induced functional recovery following SCI. Spontaneous functional recovery is reported to be greater early in life, raising interesting questions about how adaptive plasticity changes as the spinal cord develops. To facilitate investigation of this dynamic, we have developed a SCI model in the neonatal mouse. The model has relevance for pediatric SCI, which is too little studied. Because neural plasticity in the adult involves some of the same mechanisms as neural plasticity in early life1, this model may potentially have some relevance also for adult SCI. Here we describe the entire procedure for generating a reproducible spinal cord compression (SCC) injury in the neonatal mouse as early as postnatal (P) day 1. SCC is achieved by performing a laminectomy at a given spinal level (here described at thoracic levels 9-11) and then using a modified Yasargil aneurysm mini-clip to rapidly compress and decompress the spinal cord. As previously described, the injured neonatal mice can be tested for behavioral deficits or sacrificed for ex vivo physiological analysis of synaptic connectivity using electrophysiological and high-throughput optical recording techniques1. Earlier and ongoing studies using behavioral and physiological assessment have demonstrated a dramatic, acute impairment of hindlimb motility followed by a complete functional recovery within 2 weeks, and the first evidence of changes in functional circuitry at the level of identified descending synaptic connections1.

This article describes a method for generating a reproducible spinal cord compression injury (SCI) in the neonatal mouse. The model provides an advantageous platform for studying mechanisms of adaptive plasticity that underlie spontaneous functional recovery.

Un ratón neonatal lesión de médula espinal de compresión Modelo

Spinal cord injury (SCI) typically causes devastating neurological deficits, particularly through damage to fibers descending from the brain to the spinal ...

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 ...

A Tissue Displacement-based Contusive Spinal Cord Injury Model in Mice

Producing a consistent and reproducible contusive spinal cord injury (SCI) is critical to minimizing behavioral and histological variabilities between experimental animals. Several contusive SCI models have been developed to produce injuries using different mechanisms. The severity of the SCI is based on the height that a given weight is dropped, the injury force, or the spinal cord displacement. In the current study, we introduce a novel mouse contusive SCI device, the Louisville Injury System Apparatus (LISA) impactor, which can create a displacement-based SCI with high injury velocity and accuracy. This system utilizes laser distance sensors combined with advanced software to produce graded and highly-reproducible injuries. We performed a contusive SCI at the 10th thoracic vertebral (T10) level in mice to demonstrate the step-by-step procedure. The model can also be applied to the cervical and lumbar spinal levels.

We introduce a tissue displacement-based contusive spinal cord injury model that can produce a consistent contusive spinal cord injury in adult mice.

Un modelo de lesión de la médula espinal contundente basado en el desplazamiento de tejidos en ratones

Producing a consistent and reproducible contusive spinal cord injury (SCI) is critical to minimizing behavioral and histological variabilities between ...