Diese Arbeit wird durch die New Jersey Kommission auf Brain Injury Forschung finanziert.

<ol>
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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. 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Die LFP hier vorgestellte Methode Modelle viele der neuropathalogical und Verhaltensstörungen Ergebnisse der leichten bis mittelschweren Schädel-Hirn-Verletzungen, weshalb es geworden ist, eine weit verbreitete Tiermodell der TBI ist moderat. Es gibt mehrere wichtige Schritte zu erwägen, um die Validität und Zuverlässigkeit dieser Technik zu erhöhen. Zum Beispiel ist es wichtig, dass nur Tiere, bei denen die Integrität der Dura nicht während der Kraniektomie kompromittiert wurde, um LFP unterzogen werden und in der Studie. Außerdem, wenn die Kraniektomie von jedem Leim oder Zement verschlossen ist, so dass ein Teil der Dura unter der Kraniektomie nicht auf die Kraft der Flüssigkeitsdruck ausgesetzt sind, sollte das Tier aus der Studie ausgeschlossen werden. Schließlich, wenn die Gleichgewichtsreflexes Zeit oder Sterblichkeit ist nicht in dem gewünschten Bereich, sollte das Tier nicht in die Studie eingeschlossen werden. Die Intensität des Druckimpulses erhöht werden, um mehr schwere Verletzungen erzeugen. Wie in Abbildung 1 gezeigt, ist die Konfiguration des LFP-Gerät relativ einfach und die Reproduzierbarkeit der Grad der Schädigung wird durch die Überwachung der Atmosphären Druck auf dem Oszilloskop erhalten. Die glatte Form der Kurve auf dem Oszilloskop Spur zeigt, dass es keine Luftblasen in der Flüssigkeit, die mit der Induktion der LFP Verletzungen stören könnten. Ein Test Puls sollte vor Induktion Verletzungen ausgeliefert werden und wenn die Oszilloskopspur nicht aufweist eine glatte Kurve, Luftblasen entfernt werden sollte. Die Dauer des Impulses beträgt ca. 20 ms, die die Induktionszeit in Crashtest-Simulationen gemessen darstellt. Verletzungen von kürzeren Pulsen sind wahrscheinlich mehr Schwerpunkte Verletzungen zu produzieren. Daher menschlichen diesem Impulsdauer Modelle TBI. Die morphologische und zelluläre Veränderungen nach LFP gehören körperliche Schädigung des Gewebes sowie eine erhöhte Anzahl von Astrozyten und Makrophagen wie in Abbildung 2 gezeigt. Es ist bekannt, dass eines der Markenzeichen der Anzeichen von Schädigungen der Hyperplasie der Astrozyten und die Bildung einer glialen Narbe ist. Die Glia-Narbe hat sich gezeigt, dass sowohl nützliche als auch schädliche Auswirkungen 24 haben. Ebenso sind Makrophagen bekannt, in verschiedenen Geweben während der Phase nach der Verletzung ansammeln, wenn der Heilungsprozess beginnt 25. So ist die erhöhte Anzahl von GFAP und MAC1 positive Zellen in den LFP-Proben relativ zu den Schein-Kontrollen ist ein Hinweis auf die Induktion von Verletzungen. Der Mangel an Ausdruck dieser Zell-spezifische Marker in sham Kontrollen zeigt, dass die chirurgische Manipulationen allein haben keine negativen Auswirkungen auf die Gesundheit des Hirngewebes und dass die Veränderungen in der Proteinexpression sind spezifisch für die Verletzung Paradigma. Die Verhaltenskonsequenzen von mild LFP in Abbildung 3 dargestellt sind kognitive und motorische Defizite. Die MWM Befunde deuten darauf hin, dass die LFP-Mäuse schließlich lernen die Aufgabe aber in einem langsameren Tempo als die Schein-Mäusen, und sie kann mich nicht erinnern die Aufgabe sowie 1 Tag nach dem Training. So sind sogar leicht verletzten Mäuse weniger effizient als die Schein-Mäusen bei Verwendung externer Signale zu verarbeiten, zu konsolidieren und zu speichern räumlichen Informationen, die bei der anschließenden Prüfung abgerufen werden müssen. Andere Hippocampus-abhängigen kognitiven Aufgaben wie konditionierte Angstreaktion haben gezeigt, dass bei Mäusen unterzogen LFP 26 beeinträchtigt werden. Schließlich ist die kürzere Latenzzeit von LFP-Mäuse gegenüber sham Mäuse in der Rotarod Paradigma fallen bis zu 3 Wochen nach der leichte Verletzung ist ein Indikator für Defizite in der integrierten vestibulomotor und Sensomotorik. Eine mittelschwere Verletzungen würden zeigen, auffälliger Veränderungen der kognitiven und motorischen Funktionen als auch von anderen Gruppen 27-30 gezeigt. In Summe ist die LFP ein gültiges Modell für den menschlichen TBI, weil sie viele der erwarteten Kriterien erfüllt. LFP bietet Konstruktvalidität, dass es erschafft die ätiologische Prozesse, die TBI beim Menschen auslösen. Insbesondere ist die Größe der Kraft-und Mortalitätsrate ähnlich der, die in leichten und mittelschweren Sport und Auto Verletzungen mit dem Vorbehalt, dass die vor der Verletzung chirurgischen Eingriffen einzigartig für die Tier-Modell erfolgt. LFP zeigt auch face validity in die LFP rekapituliert viele anatomische, biochemische, neuropathologischen und Auswirkungen auf das Verhalten in menschlichen TBI beobachtet. Es gibt sowohl fokale und diffuse Veränderungen nach LFP erkannt und die Lateralisation der Auswirkungen ermöglicht es, die morphologische Schäden auf der Seite ipsilateral zur Schädigung, die auf der Gegenseite zu vergleichen. Ein Nachteil ist, dass die kognitiven und motorischen Wirkungen können subtiler als Folge einer Verletzung nur eine Hemisphäre. Schließlich zeigt LFP prognostische Validität und die Zuverlässigkeit der LFP-Technik ermöglicht die Auswertung von verschiedenen pharmakologischen und genetischen Manipulationen vor oder nach der Induktion von Verletzungen 20. Physiologische Variablen wie Blutdruck, Blut-pH und BlutGase müssen in der Gegenwart und Abwesenheit einer Testsubstanz auf den Wirkmechanismus eines therapeutischen Wirkstoffs zu ermitteln gemessen werden. Aufgrund der komplexen Natur der primären und sekundären Folgen der TBI ist es eine schwierige Aufgabe, eine einzige Intervention, die alle Symptome zu mildern identifizieren können. Eine künftige Überlegungen für LFP-Technik kann der Einsatz von Mikro-Fluid-Percussion, die von einem Mikroprozessor gesteuerten, pneumatisch angetriebene Gerät verwendet, um die Notwendigkeit für die Kalibrierung der Kraft, die durch das Pendel geliefert zu beseitigen und Betriebsgrößen wie Luftblasen zu vermeiden, in die Flüssigkeit 15. . Allerdings hat die Standard-LFP-Ansatz von vielen Forschern nachgewiesen worden, um eine zuverlässige und einfache Technik, um die molekularen Mechanismen der Schädigung und Erholung nach TBI was zu einer besseren Interventionen und Therapien führen zu erkunden.

<ul><li> Stereotaktische Ausrichtung Instrument für Mäuse (Kopf Instruments) </li><li> Maus Gas Anästhesie Kopfhalter (Kopf Instruments) </li><li> Anästhesie-Maschine mit O 2 flush (Parkland Scientific) </li><li> Anästhesie-Maschine mit O2-Flush (Parkland Scientific) </li><li> Buprenorphrine (Webster Tiere Supply) </li><li> Refresh Tränenflüssigkeit Lube Augensalbe (Fisher) </li><li> Bupivacain / Marcain (Webster Tiere Supply) </li><li> Povidon-Iod-Lösung (Fisher) </li><li> 20 g 1 ½ &quot;Nadeln (Becton Dickinson) </li><li> Skalpell (# 15) und Halter (Becton Dickinson) </li><li> Bulldogklemmen (Fine Science Tools) </li><li> Dental-Tool oder Knochen Schaber (Fine Science Tools) </li><li> Side Fasszange Dumont Nr. 6 (Fine Science Tools) </li><li> 3mm Außendurchmesser Trepan (Research Instrumentation Shop, University of Pennsylvania) </li><li> Solide Nylonschnur (1,7 mm Durchmesser, z. B. Unkraut Trimmer Linie) </li><li> Sekundenkleber Gel </li><li> Loctite Sekundenkleber (Loctite 444 Tak Pak) (Henkel Corporation) </li><li> Jet Acrylic Liquid (Butler Schein) </li><li> Perm Reline / Reparatur-Harz (Butler Schein) </li><li> Speicher Oszilloskop TDS 1001B, 40 MHz, 500MS / s (Tektronix) </li><li> Trauma Inducer Druckaufnehmer Amplifier (Custom Design und Fertigung, Virginia Commonwealth University) </li><li> LFP-Gerät (Custom Design und Fertigung, Virginia Commonwealth University) </li><li> Hochdruck-Schlauch, Länge 41cm, Volumen 2ml (Baxter) </li><li> 3M Vetbond Gewebekleber (Fisher) </li></ul>

lateral fluid percussion: model of traumatic brain injury in mice

Schädel-Hirn-Trauma (SHT) Forschung erreicht hat neue Impulse durch die zunehmende Sensibilisierung von Kopfverletzungen, die sich in Morbidität und Mortalität. Basierend auf der Natur der primären Verletzung nach TBI, komplexen und heterogenen sekundäre Folgen nach sich ziehen, die durch regenerative Prozesse 1,2 eingehalten werden. Primäre Verletzungen können durch eine direkte Prellung des Gehirns aus Schädelbruch oder von Scher-und Streckung des Gewebes verursacht Verschiebung des Gehirns durch die Bewegung 3,4 induziert werden. Die daraus resultierende Hämatome und Platzwunden zu einer vaskulären Antwort 3,5 und die morphologische und funktionelle Schäden der weißen Substanz führt zur axonalen Verletzungen 6-8 diffundieren. Zusätzliche sekundäre Veränderungen häufig in das Gehirn zu sehen sind Ödeme und erhöhtem Hirndruck 9. Nach TBI sind mikroskopische Veränderungen in biochemischen und physiologischen Wege unter Beteiligung der Freisetzung von Neurotransmittern excitotoxic, Immunmediatoren und Sauerstoffradikale 10-12, die letztlich in langfristigen neurologischen Behinderungen 13,14 führen. So die Auswahl geeigneter Tiermodelle der TBI vorhandenen ähnlichen zellulären und molekularen Vorgänge im menschlichen und Nagetier TBI von entscheidender Bedeutung für die Untersuchung der Mechanismen, die Verletzung und Reparatur ist. Verschiedene experimentelle Modelle der TBI wurden entwickelt, um Aspekte der TBI in Menschen beobachtet zu reproduzieren, unter ihnen drei spezifische Modelle sind häufig für Nager angepasst: fluid percussion, kortikale Einfluss und Gewicht fallen / Auswirkungen Beschleunigung 1. Die Flüssigkeit Percussion Gerät erzeugt eine Verletzung durch eine Kraniektomie durch die Anwendung einer kurzen Flüssigkeitsdruck Impuls auf die intakte Dura. Der Impuls wird durch ein Pendel Anschlagen der Kolben aus einem Reservoir der Flüssigkeit erzeugt. Das Schlagzeug erzeugt kurze Verschiebung und Verformung von Nervengewebe 1,15. Umgekehrt liefert kortikalen Auswirkungen Verletzungen mechanischer Energie auf die intakte Dura über eine starre Schlagkörper unter pneumatischem Druck 16,17. Das Gewicht fallen / Auswirkungen Modell ist durch den Fall eines Stabes mit einer bestimmten Masse auf die geschlossenen Schädel 18 gekennzeichnet. Unter den TBI-Modelle, ist LFP den etabliertesten und am häufigsten verwendeten Modell gemischt fokale und diffuse Hirnschädigung 19 zu bewerten. Es ist reproduzierbar und ist standardisiert für die Manipulation von Verletzungen Parameter ermöglichen. LFP rekapituliert Verletzungen beobachtet bei Menschen, wodurch es klinisch relevant, und ermöglicht die Erforschung und Entwicklung neuartiger Therapien für die klinische Übersetzung 20. Wir beschreiben die detaillierte Protokoll LFP Verfahren bei Mäusen durchzuführen. Die Verletzung zugefügt wird leicht bis mittelschwer, mit Hirnregionen wie Kortex, Hippocampus und Corpus Callosum am meisten gefährdet. Hippocampus und des motorischen Lernens Aufgaben sind folgende LFP erforscht.

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Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

Lateral Flüssigkeit Schlagzeug (LFP), einem etablierten Modell der Hirn-Trauma, bei Mäusen nachgewiesen ist. LFP erfüllt drei wesentliche Kriterien für die Tiermodelle: Validität, Zuverlässigkeit und klinische Relevanz. Das Verfahren, bestehend aus chirurgischen Kraniotomie, gefolgt Fixierung der Nabe durch die Induktion von Verletzungen, die sich in fokale und diffuse Verletzungen, beschrieben wird.

Lateral Fluid-Percussion: Modell Schädel-Hirn-Verletzungen in Mäuse

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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40.4K Aufrufe.  University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School. Lateral Flüssigkeit Schlagzeug (LFP), einem etablierten Modell der Hirn-Trauma, bei Mäusen nachgewiesen ist. LFP erfüllt drei wesentliche Kriterien für die Tiermodelle: Validität, Zuverlässigkeit und klinische Relevanz. Das Verfahren, bestehend aus chirurgischen Kraniotomie, gefolgt Fixierung der Nabe durch die Induktion von Verletzungen, die sich in fokale und diffuse Verletzungen, beschrieben wird.

Serie: 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.

Eine Methode, um geschlossene Kopftraumatische Hirnverletzung in Verursacht<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 ...

Forschung

Neurowissenschaften

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.

Neuronalen Aktivität im primären somatosensorischen Cortex mit Thy1Imaging-GCaMP6s transgene Mäuse

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.

Automatisierte Ganganalyse bei Mäusen mit chronischen Verengung Verletzungen

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.

Eine neuartige In-vitro- Modell von traumatischen Hirnverletzungen Blast

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.

Auswirkungen der Explosion-induzierte Neurotrauma auf Druck Nagetier mittlerer Hirnarterien

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.

Untersuchung von Veränderungen in Caecum Microbiota nach traumatischen Hirnverletzungen bei Mäusen

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.

Advanced Diffusion Imaging im Hippocampus von Ratten mit leichter traumatischer Hirnverletzung

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.

Murine Modell der kontrollierten kortikalen Auswirkungen für die Induktion von traumatischen Hirnverletzungen

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.

Low-Intensity Blast Wave Model for Preclinical Assessment of Closed-Head Mild Traumatic Brain Injury bei Nagetieren

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.

Elektromagnetisch gesteuertes Closed-Head-Modell für leichtes Schädel-Hirn-Trauma bei Mäusen

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