Animal models of traumatic brain injury: A critical evaluation (original) (raw)
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NeuroRX, 2005
Animal models of traumatic brain injury (TBI) are used to elucidate primary and secondary sequelae underlying human head injury in an effort to identify potential neuroprotective therapies for developing and adult brains. The choice of experimental model depends upon both the research goal and underlying objectives. The intrinsic ability to study injuryinduced changes in behavior, physiology, metabolism, the blood/tissue interface, the blood brain barrier, and/or inflammatory-and immune-mediated responses, makes in vivo TBI models essential for neurotrauma research. Whereas human TBI is a highly complex multifactorial disorder, animal trauma models tend to replicate only single factors involved in the pathobiology of head injury using genetically well-defined inbred animals of a single sex. Although such an experimental approach is helpful to delineate key injury mechanisms, the simplicity and hence inability of animal models to reflect the complexity of clinical head injury may underlie the discrepancy between preclinical and clinical trials of neuroprotective therapeutics. Thus, a search continues for new animal models, which would more closely mimic the highly heterogeneous nature of human TBI, and address key factors in treatment optimization.
Experimental traumatic brain injury models in rats
Zenodo (CERN European Organization for Nuclear Research), 2023
Head traumas are high-mortality pathologies that can disable. Traumatic brain injury (TBI) is a heterogeneous disease containing brain damage caused by external effects. In the human brain injury after trauma, examinations cannot be made at histopathological and molecular levels, and the effect of a new drug on a head-trauma person cannot be examined. Human models are required to experimentally reveal the similarities of human TBI's biomechanical, cellular, and molecular events and to develop new treatments and show their effectiveness. Today, the most commonly used animals in TBI experiments are rats. Rats are preferred because their volumes are small and their costs are low, and the working groups can be enlarged. In this study, the commonly used rat TBI models and the restrictions of these models were compiled.
Models of Traumatic Brain Injury
European Journal of Trauma, 2000
We present a review of the currently popular preclinical models of non-penetrating traumatic brain injury (TBI). This article focuses on animal models that cause TBI by applying mechanical energy to the head, skull or dura. It attempts to provide a compendium of the main characteristics of each of these experimental models of TBI in respect to acute and chronic histological findings and behavioral impairment in neurologic motor and cognitive function. Finally, several limitations of the described models are discussed briefly.
A preclinical model of heterogeneous traumatic brain injury
2019
Traumatic brain injury (TBI) is a leading cause of death and disability, but the factors affecting clinical outcomes following TBI are complex. Animal TBI models are widely used, but many design parameters go largely unreported. We evaluate the effects of one such parameter, head support foam type, on injury outcome in rats. We hypothesize that TBI severity is increased on stiffer foams. TBI was delivered to the closed head using a controlled cortical impact (CCI) device. We analyzed injury biomechanics on four foams using an accelerometer and high-speed video, and performed histopathology to evaluate tissue response. Our results show that foam type can significantly affect impact biomechanics, as well as cellular outcomes, and that more thorough reporting is important.M.S
Models of Rodent Cortical Traumatic Brain Injury
Neuromethods, 2011
The absence of a pharmacological therapy that is effective in the treatment of traumatic brain injury (TBI) highlights the need for further research into the secondary mechanisms that are initiated by the traumatic event, and which determine eventual neurological outcome. Various animal models of TBI exist, with each attempting to replicate different aspects of human brain injury. If an effective pharmacological therapy is to be developed and accepted by the neurotrauma community, it is critical that there is consistency across various laboratories in how these models are applied. The present review critically analyses the benefits and pitfalls of the common rodent models of TBI that are widely used today.
Development of a Rodent Model of Closed Head Injury: The Maryland Model
Neuromethods, 2018
Brain injury due to closed frontal head impact is a common mechanism in civilian traumatic brain injury (TBI). Researchers have developed a variety of models of traumatic brain injury in rodents, using both open and closed methods of injury. However, these models fail to reproduce the frontal impact of force commonly found in human TBI, result in significant focal injury such as skull fractures or focal contusions, and, in certain cases, carry an unacceptably high mortality. The Maryland TBI model provides an alternative rodent model to address these shortcomings. Here, we describe the rationale for the development of the Maryland TBI model. We then provide a detailed procedural overview of the model. We then summarize relevant pathological findings in the model. Finally, we compare the model to other existing closed head injury models in rodents, both with regard to advantages and limitations of the model.
Experimental models of traumatic brain injury: Do we really need to build a better mousetrap
Neuroscience, 2005
Approximately 4000 human beings experience a traumatic brain injury each day in the United States ranging in severity from mild to fatal. Improvements in initial management, surgical treatment, and neurointensive care have resulted in a better prognosis for traumatic brain injury patients but, to date, there is no available pharmaceutical treatment with proven efficacy, and prevention is the major protective strategy. Many patients are left with disabling changes in cognition, motor function, and personality. Over the past two decades, a number of experimental laboratories have attempted to develop novel and innovative ways to replicate, in animal models, the different aspects of this heterogenous clinical paradigm to better understand and treat patients after traumatic brain injury. Although several clinically-relevant but different experimental models have been developed to reproduce specific characteristics of human traumatic brain injury, its heterogeneity does not allow one single model to reproduce the entire spectrum of events that may occur. The use of these models has resulted in an increased understanding of the pathophysiology of traumatic brain injury, including changes in molecular and cellular pathways and neurobehavioral outcomes. This review provides an up-to-date and critical analysis of the existing models of traumatic brain injury with a view toward guiding and improving future research endeavors.
Animal Models and the Search for Drug Treatments for Traumatic Brain Injury
2020
This chapter focuses on the use of animals in research into traumatic brain injury. It begins with a brief consideration of the epidemiology of human brain injury, before examining the various ways in which animals are used to “model” human brain injuries. The bulk of the chapter explores the impact of preclinical animal research on the treatment of human traumatic brain injury. Bearing in mind this impact, the ethics of animal research into traumatic brain injury are discussed, as is the adequacy of current regulatory frameworks. Before concluding, advances in human-relevant (non-animal) approaches to investigating human traumatic brain injury are briefly considered.
This report describes the development of an experimental head injury model capable of producing diffuse brain injury in the rodent. A total of 161 anesthetized adult rats were injured utilizing a simple weight-drop device consisting of a segmented brass weight free-falling through a Plexiglas guide tube. Skull fracture was prevented by cementing a small stainless-steel disc on the calvaria. Two groups of rats were tested: Group 1, consisting of 54 rats, to establish fracture threshold; and Group 2, consisting of 107 animals, to determine the primary cause of death at severe injury levels. Data from Group 1 animals showed that a 450-gin weight falling from a 2-m height (0.9 kg-m) resulted in a mortality rate of 44% with a low incidence (12.5%) of skull fracture. Impact was followed by apnea, convulsions, and moderate hypertension. The surviving rats developed decortication flexion deformity of the forelimbs, with behavioral depression and loss of muscle tone. Data from Group 2 animals suggested that the cause of death was due to central respiratory depression; the mortality rate decreased markedly in animals mechanically ventilated during the impact. Analysis of mathematical models showed that this mass-height combination resulted in a brain acceleration of 900 G and a brain compression gradient of 0.28 ram. It is concluded that this simple model is capable of producing a graded brain injury in the rodent without a massive hypertensive surge or excessive brain-stem damage. KEY WOROS 9 head injury 9 pathophysiology biomeehanics 9 experimental model rat
A new model of diffuse brain injury in rats
Journal of Neurosurgery, 1994
✓ This report describes the development of an experimental head injury model capable of producing diffuse brain injury in the rodent. A total of 161 anesthetized adult rats were injured utilizing a simple weight-drop device consisting of a segmented brass weight free-falling through a Plexiglas guide tube. Skull fracture was prevented by cementing a small stainless-steel disc on the calvaria. Two groups of rats were tested: Group 1, consisting of 54 rats, to establish fracture threshold; and Group 2, consisting of 107 animals, to determine the primary cause of death at severe injury levels. Data from Group 1 animals showed that a 450-gm weight falling from a 2-m height (0.9 kg-m) resulted in a mortality rate of 44% with a low incidence (12.5%) of skull fracture. Impact was followed by apnea, convulsions, and moderate hypertension. The surviving rats developed decortication flexion deformity of the forelimbs, with behavioral depression and loss of muscle tone. Data from Group 2 anima...