| 1. |
- Clausen, Fredrik, et al.
(författare)
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The Fluid Percussion Injury Rodent Model in Preclinical Research on Traumatic Brain Injury
- 2019
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Ingår i: Animal Models of Neurotrauma. - New York, NY : Springer New York. - 1940-6045 .- 0893-2336. - 9781493997091 - 9781493997114 ; 149, s. 3-18
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Bokkapitel (refereegranskat)abstract
- There is still a lack of pharmacological treatment options for traumatic brain injury (TBI), the dominant cause of death and disability in persons under the age of 40 in the developed part of the world. Clinical TBI is a markedly complex disease, categorized into different subtypes that differ in their pathophysiology, treatment requirements, and long-term consequences. For successful development of novel treatment options, refined preclinical evaluation in rodent TBI models is mandatory. Since persisting cognitive deficits, impaired motor function, depression, and personality changes are common sequelae in TBI patients, preclinical models must produce clinically relevant behavioral deficits. Additionally, clinical TBI is a markedly heterogeneous disease with a severity span from immediately fatal to mild injuries with minor and passing symptoms. Ideally, a rodent TBI model should thus be adjustable in terms of injury severity. One of the most widely used rodent TBI model is the fluid percussion injury (FPI), which meets many of the criteria for a clinically relevant experimental model. The FPI technique relies on a fluid pressure pulse being transmitted into the skull cavity of the animal, allowing for a degree of brain displacement. By placing the craniectomy and the injury site either over the midline of the skull (the central FPI; cFPI) or over one hemisphere (the lateral FPI; lFPI) the injury shows either more diffuse (cFPI) or more focal (lFPI) characteristics. Although FPI has many advantages over other TBI models, including the possibility to vary important injury characteristics, the outcome after TBI may be influenced by other features such as gender, age, species, and even strain which should be considered in the design of the rodent models. In this chapter, we discuss the limitations and advantages, as well as the special considerations necessary when using the FPI model in rodents.
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| 2. |
- Dahlin, Lars B., et al.
(författare)
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Traumatic Peripheral Nerve Injuries : Experimental Models for Repair and Reconstruction
- 2019
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Ingår i: Animal Models of Neurotrauma. - New York, NY : Springer New York. - 0893-2336 .- 1940-6045. - 9781493997114 - 9781493997091 ; 149, s. 169-186
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Bokkapitel (refereegranskat)abstract
- Peripheral nerve injuries are difficult to treat, and the clinical outcome after surgical repair and reconstruction is still insufficient, particularly concerning recovery of sensory function. To improve the clinical treatment strategies, experimental models are used to systematically examine the mechanisms behind nerve regeneration and assess the improvement of nerve regeneration by introduction of new surgical nerve repair and reconstruction methods (e.g., novel devices made by bioartificial materials). Rat models, where the sciatic nerve has essentially a similar size as a human digital nerve, are widely used to evaluate nerve regeneration with the inherent advantages and disadvantages of the experimental models. Estimations revealing that a large number of diabetic patients will eventually suffer from peripheral nerve injury have motivated development of suitable experimental diabetes models for studying the nerve regeneration process and novel treatment approaches. We have successfully used the Goto-Kakizaki rat model, which shows moderately increased blood sugar closely resembling type 2 diabetes, for assessing the surgical peripheral nerve regeneration potential with and without artificial scaffolds. In order to improve outcome after repair and reconstruction of nerve injuries, one has to have a clear concept concerning how to evaluate novel repair and reconstruction techniques in experimental models before clinical studies can be initiated in an accurate way.
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| 3. |
- Davidsson, Johan, 1967, et al.
(författare)
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Characterisation of the pressure distribution in penetrating traumatic brain injuries
- 2015
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 6:51, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Severe impacts to the head commonly lead to localized brain damage. Such impacts may also give rise to temporary pressure changes that produce secondary injuries in brain volumes distal to the impact site. Monitoring pressure changes in a clinical setting is difficult; detailed studies into the effect of pressure changes in the brain call for the development and use of animal models.The aim of this study is to characterize the pressure distributionin an animal model of penetrating traumatic brain injuries (pTBI). This data may be used to validate mathematical models of the animal model and to facilitate correlation studies between pressure changes and pathology. Pressure changes were measured in rat brains while subjected to pTBI for a variety of different probe velocities and shapes; pointy, blunt, and flat. Experiments on ballistic gel samples were carried out to study the formation of any temporary cavities. In addition, pressure recordings from the gel experiments were compared to values recorded in the animal experiments. The pTBI generated short lasting pressure changes in the brain tissue; the pressure in the contralateral ventricle (CLV) increased to 8 bar followed by a drop to 0.4 bar when applying flat probes. The pressurechanges in the periphery of the probe, in the Cisterna Magna, and the spinal canal, were significantly less than those recorded in the CLV or the vicinity of the skull base. Highspeed videos of the gel samples revealed the formation of spherically shaped cavities when flat and spherical probes were applied. Pressure changes in the gel were similar to those recorded in the animals, although amplitudes were lower in the gel samples. We concluded cavity expansion rate rather than cavity size correlated with pressure changes in the gel or brain secondary to probe impact. The new data can serve as validation datafor finite element models of the trauma model and the animal and to correlate physical measurements with secondary injuries.
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| 4. |
- Davidsson, Johan, 1967, et al.
(författare)
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Experimental Models for Neurotrauma Research
- 2016
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Ingår i: Methods in Molecular Biology. - 1940-6029 .- 1064-3745. ; 1462, s. 267-88
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Tidskriftsartikel (refereegranskat)abstract
- Physical trauma in the central nervous system (CNS) is usually the result of a number of forces in different directions and dimensions. A large number of experimental models have been developed to improve the possibilities to understand the outcome of CNS trauma. In this chapter, we will describe the need for a variety of experimental models for research on traumatic brain injury (TBI) and spinal cord injury (SCI). Models can serve different needs, such as: to test new treatments for injuries, to reveal thresholds for injuries, to provide a better understanding of injury mechanisms, or to test tools and methods for translation between experiments and clinical data. In this chapter, we will discuss on the validation of models and translation between experimental and clinical studies.
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| 5. |
- Davidsson, Johan, 1967, et al.
(författare)
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Experiments and Mathematical Modeling for Evaluation of Non-Lethal Weapons
- 2015
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Ingår i: 8th European Symposium on Non-lethal Weapons, May 18-20, Ettlingen, Germany. ; , s. V21-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The biomechanical response of new and existing non-lethal weapons (NLWs) are to be determined to assess their effectiveness and safety, i.e. the type of injury produced and the risk of such injuries, for the target population and bystanders. The effect and risk of injury varies widely for most NLWs (from no effect to lethality) depending on how the weapon is used, the body region hit and variability in biomechanical response between humans. Commonly the effectiveness and safety provided by a particular NLW are assessed using real-life data from situations in which the NLW have been employed. However, for new NLWs it is necessary to conduct experimental studies using modelsof the human such as anthropometric tests devises (ATDs) and Human Body Models (HBM), post mortem human subjects (PMHSs), animals and cell cultures.While the assessment of possible NLW related injuries in ATDs and PMHSs are crude, animals and cell cultures are excellent for studies of injury mechanisms and injury criteria. For some injuries these mechanisms and criteria can be scaled to humans. The obtained data can also be used in the development of injury risk functions for humans but commonly require scaling. Several of the scaling techniques used in the past are crude. Computer simulation with finite element technique can be used to improve the understanding of experimental studies and to construct injury risk functions at tissue level using data from animal or cell culture experiments. The tissue risk functions can then be used in finite element models of humans to support the development of global injury criteria; to enable theevaluation of new NLWs using ATDs. In this paper we will describe animal models used to study mild and moderate brain injuries and associated finite element models. The paper aims at illustrating the benefit of combining models in biomechanics research and proving guidelines for such studies.
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| 6. |
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| 7. |
- McKay, Kyla, et al.
(författare)
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Environmental risk factors for amyotrophic lateral sclerosis (ALS) in a military context
- 2019
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Ingår i: The 13th CBRNe Protection Symposium.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- ALS is a rare disease with an incidence worldwide of 2-3 persons per 100 000 inhabitants. However, an increase in incidence among military personell has been identified in several studies. Approximately 10% of the ALS cases are inherited (familiar ALS); the remaining cases might be due to a combination of genetic and environmental factors (sporadic ALS). The most likely hypothesis regarding the onset of ALS is accumulation of incorrectly folded proteins around neurons in the brain. Incorrect protein folding may be due to a mutation in the enzyme SOD1. Such mutations can be initiated if the cell is exposed to prolonged physiological or environmental stress, for example from prolonged extreme physical exercise. Epidemiologically substantiated risk factors for ALS include lead exposure, head trauma, extreme physical training, pesticide exposure and exposure to electromagnetic radiation. In addition, toxins from cyanobacteria has been discussed as a potential risk factor. Military personnel constitute a typical occupational group with low grade, sometimes long-lasting and parallel exposure to several of the relevant environmental riskfactors. For example, correlations between elevated levels of lead in the blood and increased risk of ALS among United States Veterans has been found, as well as a correlation with exposure to pesticides. In addition, correlation of ALS incidence with head trauma incidents have been suggested. The inflammation that might occur locally after repeated hard physical exertion and/or repeated mild trauma can lead to oxidative stress in the cell. It is known that oxidative stress may cause corrupted/incorrectly folded proteins. These correlations can be part of the explanation for the increased risk of ALS seen in groups exposed to hard physical exertion and/or repeated mild trauma, such as military personnel and athletes. This presentation constitutes a review of epidemiologic data from military environments and also present result from environmental sampling of soils in Timbuctoo.The conclusion that can be drawn from sampling the environment in Timbuctoo is that it is unlikely that the personnel who reside in and around camp Nobel are exposed to cyanobacteria and their toxins
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| 8. |
- Paban, Véronique, et al.
(författare)
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Molecular gene expression following blunt and rotational models of traumatic brain injury parallel injuries associated with stroke and depression
- 2016
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Ingår i: Journal of Translational Science. - 2059-268X. ; 2:6, s. 330-339
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) is associated with a collection of physical, emotional and cognitive post complications. The background for such complex consequences may be due to a number of different factors, and the nature of these changes indicates that the frontal lobes may be implicated. In this study we have employed gene expression arrays and gene ontology databases to search for possible similarities between different forms of acquired brain injuries in order to test whether molecular relationships exist between the different pathologies. Two types of experimental models for traumatic brain injuries, lateral fluid percussion and rotational acceleration, were used. Their molecular signature was identified and compared with those related to other rodent models simulating stress, depression, alcohol dependence, stroke, and Alzheimer’s disease. The data show that the two TBI models share similar gene expression changes with the models with regard to depression and stroke, indicating a common molecular support between these pathologies. The data provided can contribute to the introduction of new treatment strategies related to TBI.
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| 9. |
- Risling, Mårten, et al.
(författare)
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Mice and (wo)men with head trauma
- 2015
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Ingår i: IHL and Gender - Swedish Experiences. - 9789163796302 ; , s. 103-110
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Risling, Mårten, et al.
(författare)
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Neurofilament light concentrations in serum following experimental rotational traumatic brain injury in rats
- 2017
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Ingår i: Neuroscience 2017. ; 392.06 / AA26, s. 18304-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The protein neurofilament light (NFL) is predominantly expressed in the long myelinated subcortical axons. Measurement of NFL in serum of athletes after head trauma have been shown to correlate with the severity of brain injury. However, experimental models that allow for studies of NFL in serum in combination with studies of structural brain injuries are limited. Therefore, the aim of this study was to measure NFL in serum from rats following experimental sagittal plane rotation trauma and to compare these measurements to data on accumulation of Amyloid Precursor Protein (APP) in the white matter following similar type and severity trauma. Spray Dawley rats (n=65) were exposed to rapid sagittal plane rotational acceleration head trauma (maximum rotational acceleration 1.40 ± 0.32 (mean ± SD, n=29). Serum samples were collected just prior to termination at 2.5, 24, 72, 120, 168 and 672 hours post trauma. The NFL serum concentration was studied using NFL immunoassay on the single molecule array (Simoa) platform. The trauma caused subdural bleedings in most animals. Staining brain tissue with APP antibodies and FD Neurosilver revealed wide spread axonal injuries in the corpus callosum, the border between the corpus callosum and cortex and in tracts in the brain stem. Only limited signs of contusion injuries were observed following trauma. Macrophage invasions, glial fibrillary acidic protein redistribution or hypertrophy, and blood brain barrier (BBB) changes were unusual. Traumatized animals exhibited increased NFL concentrations compared to sham exposed animals for all survival times; for survival times 24 h the increase was 8 times (exposed 666 pg/mL (range 327 to 1421 pg/mL) sham 83 pg/mL (range 40 to 114 pg/mL). The shorter and longer survival times resulted in lesser increase. At 2.5 hours and 28 days post trauma the NL serum concentration increase were approximately 2.5 times. The measured NFL leakage to the blood system appear to occur despite the absence of obvious BBB injuries. Serum NFL concentration appear to correlate with APP level in the white matter for all time points studied. In conclusion NFL serum concentrations in experimental trauma was more prominent than those reported following sports-related concussion and when using the same immunoassay technique. This study supports the hypothesis that mild rotational trauma is associated with acute axonal injury and serum NFL may offer diagnostic utility for such trauma. NFL serum level increased following trauma despite no apparent BBB injury.
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