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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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| 3. |
- 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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| 4. |
- 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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| 6. |
- 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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| 7. |
- Ekmark Lewén, Sara, 1978-
(författare)
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Cellular Reactions and Behavioral Changes in Focal and Diffuse Traumatic Brain Injury : A Study in the Rat and Mouse
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Traumatic brain injury (TBI) is a severe condition and a major cause of death and disability. There is no pharmacological treatment available in clinical practice today and knowledge of brain injury mechanisms is of importance for development of neuroprotective drugs. The aims of the thesis were to get a better understanding of astrocyte reactions and immune responses, as well as behavioral changes after focal unilateral cortical contusion injury and diffuse bilateral central fluid percussion injury in rats and mice.In the focal injury models, the astrocyte reactions were generally restricted to the ipsilateral hemisphere. After diffuse TBI, vimentin and glial fibrillary acidic protein (GFAP) positive reactive astrocytes were bilaterally expressed in brain regions even distant from the injury site, including regions where axonal injury was seen. Early after diffuse TBI, there was a robust immune response, including activation of macrophages/microglia (Mac-2+) and infiltration of neutrophils (GR-1+) and T-cells (CD3+).In order to measure functional outcome, the recently established Multivariate Concentric Square Field™ (MCSF) test for complex behaviors, including risk taking and explorative strategies was used. The Morris water maze (MWM) was applied for testing learning and memory. The MCSF test revealed alterations in risk taking, risk assessment and exploratory behavior, in the mice subjected to focal injury whereas mice subjected to the diffuse injury showed a deviant stereotyped behavior. After focal injury mice showed a decreased ability to adapt to the arena in the second trial, when tested repeatedly in the MCSF test. Mice subjected to diffuse injury had an impaired memory but not learning, in the MWM test. Post-injury treatment with the anti-inflammatory anti-interleukin-1β (IgG2 a/k) antibody showed a positive effect on functional outcome in the diffuse injury model. Altogether, the results demonstrate that focal and diffuse TBI models produce differences in cellular reactions and behavioral outcome and that the immune response plays a key role in the pathology after brain injury.
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| 9. |
- Günther, Mattias, et al.
(författare)
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Cox‐2 Regulation Differs Between Sexes in the Secondary Inflammatory Response Following Experimental Penetrating Focal Brain Injury in Rats
- 2014
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Ingår i: Journal of Neurotrauma. ; 31:5, s. A-18
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Traumatic brain injury (TBI) is followed by secondary neuronal degeneration, largely dependent on an inflammatory response. This response is probably gender specific, since females are generally better protected than males in animal models and human epidemiological studies of TBI. The reasons are not fully known. We examined aspects of the inflammatory response following experimental TBI in male and female rats to explore possible gender differences. A penetrating brain injury model was used to produce focal TBI in male (n=10) and female (n=10) rats. After 24 h and 72 h the brains were removed and subjected to immunohistochemical analyses and in situ hybridization. Cox‐2 mRNA was elevated in the perilesional area compared to the un‐injured contralateral side, and significantly higher in males compared to females at 24 h and 72 h (p
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| 10. |
- Günther, Mattias, et al.
(författare)
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Neuroprotective effects of N-acetylcysteine amide on experimental focal penetrating brain injury in rats
- 2014
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Ingår i: Neuroscience Meeting, Washington DC, 2014 Nov 15-21. ; , s. 486.06-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background The beneficial effects of N-acetylcysteine (NAC) on CNS ischemia and after TBI in animal models are well documented. However, the bioavailability of NAC is very low. N-acetylcysteine Amide (NACA) is a newly modified form of N-acetylcysteine that contains an amide group in place of the carboxyl group of NAC. NACA has more efficient membrane permeation and crosses the blood brain barrier. We examined the effects of NACA in the secondary inflammatory response following focal penetrating TBI in rats. Material and methods Focal penetrating TBI were produced in a total of 24 male Sprague-Dawley rats randomly selected for treatment (n=5), non-treatment (n=5) and sham (n=4). The treated animals were given NACA 300 mg/kg ip after 5 min and in the 24h survival group a bolus of 300 mg/kg ip after 4h. After 2h and 24h the brains were removed, cut in 14 µm coronal sections and subjected to immunohistochemistry, immunofluorescence, Fluoro-Jade and TUNEL analyses. Results NACA treatment decreased neuronal degeneration by Fluoro-Jade at 24h (p
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