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| 2. |
- Antona, Jacobo, 1981, et al.
(författare)
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Validation of local brain kinematics of a novel rat brain finite element model under rotational acceleration and its application towards the clarification of Diffuse Axonal Injury mechanisms
- 2013
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Ingår i: Proceeding of JSAE Annual Congress, Yokohama, Japan.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Relative brain-skull displacement under head rotational acceleration in rats was evaluated experimentally. For this, a thin pin was entered the cortex and rigidly attached to the skull prior to impact. For peak rotational accelerations of 1.7 Mrad/s2, the pin scarred the brain cortex; 1.2 mm superficially and less centrally. These measurements were used to validate the brain kinematics of a new anatomically detailed FE model of the head-neck complex of a rat. This model is intended to be used to clarify brain loading mechanisms and to develop brain tissue injury threshold for Diffuse Axonal Injuries as detected through immune-histology.
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| 4. |
- 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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| 5. |
- 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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| 6. |
- Davidsson, Johan, 1967, et al.
(författare)
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A new model to produce sagittal plane rotational induced diffuse axonal injuries
- 2011
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Ingår i: Frontiers in Neurology. - 1664-2295. ; 2:41, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- A new in vivo animal model that produces diffuse brain injuries in sagittal plane rearward rotational acceleration has been developed. In this model, the skull of an anesthetized adult rat is tightly secured to a rotating bar. During trauma, the bar is impacted by a striker that causes the bar and the animal head to rotate rearward; the acceleration phase last 0.4ms and is followed by a rotation at constant speed and a gentle deceleration when the bar makes contact with a padded stop.The total head angle change is less than 30˚. By adjusting the air pressure in the rifle used to accelerate the striker, resulting rotational acceleration between 0.3 and 2.1 Mrad/s2 can be produced. Numerous combinations of trauma levels, post-trauma survival times, brain and serum retrieval, and tissue preparation techniques were adopted to characterize this new model. The trauma caused subdural bleedings in animals exposed to severe trauma. Staining brain tissue with β-Amyloid Precursor Protein antibodies and FD Neurosilver that detect degenerating axons revealed wide spread axonal injuries (AI) in the corpus callosum, the border between the corpus callosum and cortex and in tracts in the brain stem. The observed AIs were apparent only when the rotational acceleration level was moderate and above. On the contrary, 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. S100 serum analyses indicate that blood vessel and glia cell injuries occur following moderate levels of trauma despite the absence of obvious BBB injuries.We conclude that this rotational trauma model is capable of producing graded axonal injury, is repeatable and produces limited other types of traumatic brain injuries and as such is useful in the study of injury biomechanics, diagnostics, and treatment strategies following diffuse axonal injury.
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| 7. |
- 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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| 8. |
- Davidsson, Johan, 1967, et al.
(författare)
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Effect of age on amount and distribution of diffuse axonal injury after rotational trauma
- 2013
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Ingår i: Proceeding of JSAE Annual Congress, Yokohama, Japan.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Injury thresholds for diffuse axonal injuries (DAI) due to rotational head trauma are being developed. However, age may influence injury risk. Understanding this relationship is necessary for the development of injury criteria for children and elderly. Here rats were exposed to sagittal plane rotational acceleration head trauma and the outcome studied using Amyloid Precursor Protein to detect axonal injuries. For relatively young animals, DAI were found in and along the border of the corpus callosum and in the brainstem when rotational acceleration exceeded 1.1 Mrad/s2. Slightly older animals required higher accelerations to exhibit similar injury levels and the injury patterns were different. In conclusion, a previous study showed that the onset of diffuse axonal injuries started to appear at 10 krad/s2 with a duration of 4 ms, when scaled for humans, whereas new data indicate that this onset is slightly higher for occupants thata atre approximately 15 years older.
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| 9. |
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| 10. |
- Davidsson, Johan, 1967, et al.
(författare)
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Effect of age on amount and distribution of diffuse axonal injury after rotational trauma
- 2014
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Traumatic brain injuries (TBI) are a major public health problem in term of suffering and cost for society. About 40% of the TBI patients admitted to hospitals are non-focal injuries, usually referred to as distributed brain injuries (DBI). Studies have hypothesized that the resulting strains in the brain tissue are the primary cause of neurological deficiencies following DBI. These strains commonly appear when the skull is accelerated and the brain mass, due to its inertia, lags behind or continues its motion relative the skull. It has been suggested that the severity of the injury correlates with the amplitude of the angular acceleration, or with the resulting angular velocity. Among DBI, diffuse axonal injury (DAI) is common and regularly results in unconsciousness or death. Past studies have suggested DAI injury criteria and thresholds that can be used with crash test dummies and mathematical models of the human. However, these past studies have been performed with rather young animals. In addition, some studies have shown that brain properties change as we grow older; it is likely that this have an effect on the risk of DAI following a rotational head injury. Therefore, the aim of this study is to investigate the distribution of axonal injuries in the brain following sagittal plane rotation trauma and to determine if the injury threshold changes when the subjects grow older. In this study rats were exposed to sagittal plane rotational acceleration head trauma and the outcome studied using Amyloid Precursor Protein to detect axonal injuries. For relatively young animals, DAI were found in and along the border of the corpus callosum and in the brainstem when rotational acceleration exceeded 1.1 Mrad/s2. Slightly older animals required higher accelerations to exhibit similar injury levels and the injury patterns were different. We hypothesise that the lower injury scores for the older subjects could be due to differences in tolerance to tissue strains or, as indicated in the literature, that the differences were due to changes in the constitutive properties of the brain tissue. The latter suggests, in combination with the observed differences between older and younger individuals, that additional studies on brain tissue properties, and studies on rotational acceleration induced DAI, should be carried out using even younger and older animals than used in this study. In conclusion, a previous study showed that the onset of diffuse axonal injuries started to appear at 10 krad/s2 with a duration of 4 ms, when data were scaled for humans, whereas new data indicate that this onset is slightly higher for occupants that are approximately 15 years older.
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