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- Angeria, Maria, et al.
(author)
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Experimental Animal Models for Studies on the Mechanisms of Blast-induced Neurotrauma
- 2012
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In: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 3:30
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Journal article (peer-reviewed)abstract
- A blast injury is a complex type of physical trauma resulting from the detonation of explosive compounds and has become an important issue due to the use of improvised explosive devices (IED) in current military conflicts. Blast-induced neurotrauma (BINT) is a major concern in contemporary military medicine and includes a variety of injuries that range from mild to lethal. Extreme forces and their complex propagation characterize BINT. Modern body protection and the development of armored military vehicles can be assumed to have changed the outcome of BINT. Primary blast injuries are caused by overpressure waves whereas secondary, tertiary, and quaternary blast injuries can have more varied origins such as the impact of fragments, abnormal movements, or heat. The characteristics of the blast wave can be assumed to be significantly different in open field detonations compared to explosions in a confined space, such an armored vehicle. Important parameters include peak pressure, duration, and shape of the pulse. Reflections from walls and armor can make the prediction of effects in individual cases very complex. Epidemiological data do not contain information of the comparative importance of the different blast mechanisms. It is therefore important to generate data in carefully designed animal models. Such models can be selective reproductions of a primary blast, penetrating injuries from fragments, acceleration movements, or combinations of such mechanisms. It is of crucial importance that the physical parameters of the employed models are well characterized so that the experiments can be reproduced in different laboratory settings. Ideally, pressure recordings should be calibrated by using the same equipment in several laboratories. With carefully designed models and thoroughly evaluated animal data it should be possible to achieve a translation of data between animal and clinical data. Imaging and computer simulation represent a possible link between experiments and studies of human cases. However, in order for mathematical simulations to be completely useful, the predictions will most likely have to be validated by detailed data from animal experiments. Some aspects of BINT can conceivably be studied in vitro. However, factors such as systemic response, brain edema, inflammation, vasospasm, or changes in synaptic transmission and behavior must be evaluated in experimental animals. Against this background, it is necessary that such animal experiments are carefully developed imitations of actual components in the blast injury. This paper describes and discusses examples of different designs of experimental models relevant to BINT.
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| 2. |
- Berg, Rand Wilcox Vanden, et al.
(author)
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Brain tissue saving effects by single-dose intralesional administration of Neuroprotectin D1 on experimental focal penetrating brain injury in rats
- 2019
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In: Journal of Clinical Neuroscience. - : Elsevier BV. - 0967-5868 .- 1532-2653. ; 64, s. 227-233
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Journal article (peer-reviewed)abstract
- Traumatic brain injury (TBI)is followed by a secondary inflammation in the brain. Neuroprotectin D1 (NPD1)is synthesized from docosahexaenoic acid (DHA)and has anti-inflammatory and antiapoptotic effects in experimental models of neurodegenerative disease and brain ischemia-reperfusion. It is not known whether intralesional administration of NPD1 ameliorates inflammation and cell death after severe TBI. We therefore investigated the effects of NPD1 following a severe form of focal penetrating TBI. A total of 30 male Sprague-Dawley rats weighing between 350 and 450 g were exposed to focal penetrating TBI or sham surgery. The rats were randomized to NPD1 treatment (50 ng intralesionally, immediately following TBI)or no treatment. The rats were sacrificed at 24 or 72 h. All subgroups consisted of 5 rats. Brains were removed, fresh frozen, cut in 14-µm coronal sections and subjected to Fluoro-Jade, TUNEL, MnSOD, 3-NT, COX-2, Ox-42 and NF-κB immuno-staining and lesion size analyses. NPD1 decreased the lesion area at 72 h compared to no treatment with a mean change 42% (NPD1 14.1 mm 2 ; no treatment 24.5 mm 2 )(p < 0.01). No difference was detected in markers for neuronal degeneration, apoptosis, anti-inflammatory or antioxidative enzymes, or immune cells. In conclusion, single-dose intralesional administration of NPD1 had brain tissue sparing effects after focal penetrating TBI, which may be beneficial in preventing brain tissue damage, making NPD1 a potential candidate for further clinical applications. Exact mechanisms of action could not be determined and it is possible that continuous or multiple administration regimens may increase efficacy in sequential preclinical studies.
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| 3. |
- Davidsson, Johan, 1967, et al.
(author)
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Effect of age on amount and distribution of diffuse axonal injury after rotational trauma
- 2013
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In: Proceeding of JSAE Annual Congress, Yokohama, Japan.
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Conference paper (other academic/artistic)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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| 4. |
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| 5. |
- Davidsson, Johan, 1967, et al.
(author)
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Effect of age on amount and distribution of diffuse axonal injury after rotational trauma
- 2014
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Conference paper (other academic/artistic)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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| 6. |
- Davidsson, Johan, 1967, et al.
(author)
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Injury threshold for sagittal plane rotational induced diffuse axonal injuries
- 2009
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In: 2009 International IRCOBI Conference on the Biomechanics of Injury; York; United Kingdom; 9 September 2009 through 11 September 2009. - 9783033020504 ; , s. 43-55
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Conference paper (peer-reviewed)abstract
- Sagittal plane rotational acceleration induced diffuse axonal injury threshold was investigated using an animal model in which the heads of the rats were exposed to selected rotation accelerations. Post-trauma survival times ranged from 3 to 120 h. Numerous S100 serum concentrations, brain tissue stained for β-Amyloid Precursor Protein (β-APP), and probes for Cyclooxygenase 2 (COX2) mRNA were used to detect affected nerve cells, decaying axons, and cytoskeletal changes, respectively. Scaling laws were applied to estimate injury thresholds for the human brain. Confocal imaging revealed bands of β-APP-positive axons in the corpus callosum and its edges in animals exposed to rotational accelerations >1.1 Mrad/s2. Similarly, for COX2 presence and S100 concentrations at >0.9 Mrad/s2, the numbers of stained cells in the cortex and hippocampus and the concentrations increased. The data clearly indicate that the rat brain is injured at a specific rotational acceleration. Scaled to that of humans this would be 10 krad/s2 with a duration of 4 ms.
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| 9. |
- Günther, Mattias, et al.
(author)
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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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In: Journal of Neurotrauma. ; 31:5, s. A-18
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Journal article (other academic/artistic)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.
(author)
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Neuroprotective effects of N-acetylcysteine amide on experimental focal penetrating brain injury in rats
- 2014
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In: Neuroscience Meeting, Washington DC, 2014 Nov 15-21. ; , s. 486.06-
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Conference paper (other academic/artistic)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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