Publications (14)37.69 Total impact
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Article: Animal model for sport-related concussion; ICP and cognitive function
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ABSTRACT: Background: We have recently developed and characterized a rat model of mild traumatic brain injury (mTBI) which simulates the concussive injuries frequently encountered by players in American professional football. Objectives: To study the effect of multiple impacts to the head on intracranial pressure, cognitive function and exploratory behavior. Materials and methods: The model was employed to cause concussion. Intracranial pressure, cognitive function and exploratory behavior were examined following the multiple impacts of a 50 or 100 g projectile at a velocity of 9.3 or 11.2 m/s to the helmet protected head. Results: Intracranial pressure measured at 6 and 10 hours, and 1, 2, 3, 5 and 7 days. It was maximally elevated 10 h after impact and returned to the control levels 7 days later. Morris Water Maze assessment 48 h after impact revealed impaired cognitive function. Open field testing 2-4 days and 1and 2 weeks after impacts indicated consistently reduced spontaneous exploratory activity. Conclusion: Multiple impacts to the head raise intracranial pressure and impair cognitive function and exploratory activity in this animal model.Acta Neurologica Scandinavica. 01/2011; -
Article: Mechanisms and pathophysiology of the low-level blast brain injury in animal models.
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ABSTRACT: The symptoms of primary blast-induced mTBI, posttraumatic stress disorder and depression overlap. Evidence of an organic basis for these entities has been scarce and controversial. We present a review of animal studies demonstrating that low-level blast causes pathophysiological and functional changes in the brain. We monitor a time period from minutes to approximately 1 week after blast exposure from multiple modes (air, underwater, localized and whole body). The most salient findings observed were (1) the peak pressures (P(max)) in the brain, elicited from the blast from the firing of military weapons (P(max) 23-45 kPa), have a similar magnitude as that registered in air close to the head. Corresponding measurements during the detonation pulse from explosives under water show a P(max) in the brain, which is only 10% of that in water outside the head. (2) The rise time of the pressure curve is 10 times longer in the brain as compared with the blast in air outside the head during firing of military weapons. (3) The lower frequencies in the blast wave appear to be transmitted more readily to the brain than the higher frequencies. (4) When animals are exposed to low levels of blast, the blast wave appears mostly transmitted directly to the brain during air exposure, not via the thorax or abdomen. (5) Low levels of blast cause brain edema, as indicated by increased bioelectrical impedance, an increase in the intracranial pressure, small brain hemorrhages and impaired cognitive function.NeuroImage 01/2011; 54 Suppl 1:S83-8. · 5.89 Impact Factor -
Article: Numerical simulation of mechanisms of blast-induced traumatic brain injury.
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ABSTRACT: Blast-induced traumatic brain injury caused by road bombs has lately become a larger part of allied injuries. The same mechanisms may also be responsible for milder injuries of similar nature, resulting from training with large caliber weapons and explosives. In this paper, the blast effects from a weapon on the brain are investigated. Using the hydrocode AUTODYN, numerical simulations of shock wave propagation into the brain are performed. The shock wave is calculated from a complete numerical simulation of the weapon, including the burning gun powder gas inside the barrel, acceleration of the projectile, and the rapid gas flow out of the muzzle. An idealized head is placed in the simulation at the position of personnel firing the weapon. Here we focus on the qualitative mechanisms of the propagation of the shock wave through the skull and into the brain. The results are compared with experiments carried out on anesthetized animals. To simulate real training scenarios, pigs were placed in position of personnel and exposed to impulse noise generated from weapons. Blast parameters in the air were correlated with those in the brain.The Journal of the Acoustical Society of America 03/2010; 127(3):1790. · 1.55 Impact Factor -
Article: Effects of low blast levels on the central nervous system.
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ABSTRACT: Anaesthetized swine in crew positions were exposed to weapons in air or to explosives underwater. Blast parameters were correlated with those in the brain. The peak pressure in the brain (Pmax brainair) was 0.7 for a bazooka (45 kPa), 0.5 for a howitzer (10 kPa), and 0.4 for a rifle (23 kPa). The brainwater Pmax for the detonation pulse of under water explosives was only 0.1, but 0.3-0.4 for the secondary pulses. The results indicate that low-frequency spectra penetrate easier into the brain. Histological examination revealed small hemorrhages in rear regions of the brain. In rats, we investigated the effect of shock tube blasts. After exposure to 10 or 30 kPa, cognitive performance (Morris Water Maze) decreased by 50%. The intracranial pressure (ICP) increased in a dose dependent fashion to reach peak levels 6 h after exposure at 10 kPa and 10 h after exposure to 30 or 60 kPa. An initial ICP elevation took place 30 min after exposure to 60 kPa, and 2 and 6 h after exposure to 30 and 10 kPa, respectively. A prophylaxis, consisting of a 2 week intake of hydrothermally fermented cereals, reduced significantly the blast effect both on ICP and cognitive performance. [The authors thanks Svante Hjer, Samba Sensors AB. The study was supported by the Swedish Armed Forces and FMV.].The Journal of the Acoustical Society of America 03/2010; 127(3):1789. · 1.55 Impact Factor -
Article: Low-level blast raises intracranial pressure and impairs cognitive function in rats: prophylaxis with processed cereal feed.
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ABSTRACT: There is increasing evidence that even low levels of blast cause brain injury, but little is known about their thresholds and mechanisms. Exposure of rats to 10-60 kPa blasts elevate intracranial pressure (ICP) in a dose-dependent manner and impair cognitive function. We have evaluated a prophylactic measure against these brain injuries in a rat animal model, consisting of feeding them processed cereal. This type of feed is known to ameliorate disturbances in secretion of body fluids and to have anti-inflammatory effects. In humans, intake of processed cereals is effective against intestinal diarrhea and also reduces the symptoms of Ménière's disease. Rats were given either standard laboratory feed or processed cereal feed for 2 weeks before exposure to blast in a shock tube. The ICP was monitored at different time points up to 1 week after exposure to a 60-kPa blast, and for up to 24 h after exposure to a 30-kPa blast. Maximal ICP elevation was reached at 10 h in both groups. In the group of rats on standard feed exposed to 60 kPa, an ICP increase of 145% was noted at 10 h, and the corresponding increase in the rats fed processed cereal feed was only 50%. In rats exposed to a 30-kPa blast, those fed standard feed and processed cereal feed demonstrated increases of ICP of 80% and 40%, respectively. Cognitive function as measured by the Morris water maze was assessed in other groups of rats at 2 days after exposure to 10- or 30-kPa blasts. Their performance was significantly impaired at both exposure levels in rats on standard feed, but no functional impairment was seen in rats fed processed cereal feed.Journal of neurotrauma 10/2009; 27(2):383-9. · 4.25 Impact Factor -
Article: Concussion in professional football: animal model of brain injury--part 15.
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ABSTRACT: A concussion model was developed to study injury mechanisms, functional effects, treatment, and recovery. Concussions in National Football League football involve high-impact velocity (7.4-11.2 m/s) and rapid change in head velocity (DeltaV) (5.4-9.0 m/s). Current animal models do not simulate these head impact conditions. One hundred eight adult male Wistar rats weighing 280 to 350 g were used in ballistic impacts simulating 3 collision severities causing National Football League-type concussion. Pneumatic pressure accelerated a 50 g impactor to velocities of 7.4, 9.3, and 11.2 m/s at the left side of the helmet-protected head. A thin layer of padding on the helmet controlled head acceleration, which was measured on the opposite side of the head, in line with the impact. Peak head acceleration, DeltaV, impact duration, and energy transfer were determined. Fifty-four animals were exposed to single impact, with 18 each having 1, 4, or 10 days of survival. Similar tests were conducted on another 54 animals, which received 3 impacts at 6-hour intervals. An additional 72 animals were tested with a 100g impactor to study more serious brain injuries. Brains were perfused, and surface injuries were identified. The 50 g impactor matches concussion conditions scaled to the rat. Impact velocity and head DeltaV were within 1% and 3% of targets on average. Head acceleration reached 450 g to 1750 g without skull fracture. The test is repeatable and robust. Gross pathology was observed in 11%, 28%, and 33% of animals in the 7.4-, 9.3-, and 11.2-m/s single impacts, respectively. At 7.4 m/s, a single diameter area of less than 0.5 mm of fine petechial hemorrhage occurred on the brain surface in the parenchyma and meninges nearest the point of impact. At higher velocities, there were larger areas of bleeding, sometimes with subdural hemorrhage. When the 50 g impactor tests were examined by logistic regression, greater energy transfer increased the probability of injury (odds ratio, 5.83; P = 0.01), as did 3 repeat impacts (odds ratio, 4.72; P = 0.002). The number of survival days decreased the probability of observing injury (odds ratio, 0.25 and 0.11 for 4 and 10 days, respectively, compared with 1 day). The 100g impactor produced more severe brain injuries. A concussion model was developed to simulate the high velocity of impact and rapid head DeltaV of concussions in National Football League players. The new procedure can be used to evaluate immediate and latent effects of concussion and more severe injury with greater impact mass.Neurosurgery 07/2009; 64(6):1162-73; discussion 1173. · 2.79 Impact Factor -
Article: Concussion in professional football: morphology of brain injuries in the NFL concussion model--part 16.
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ABSTRACT: An animal model of concussions in National Football League players has been described in a previous study. It involves a freely moving 300-g Wistar rat impacted on the side of the head at velocities of 7.4 to 11.2 m/s with a 50-g impactor. The impact causes a 6% to 28% incidence of meningeal hemorrhages and 0.1- to 0.3-mm focal petechiae depending on the impact velocity. This study addresses the immunohistochemical responses of the brain. Twenty-seven tests were conducted with a 50-g impactor and velocities of 7.4, 9.3, or 11.2 m/s. The left temporal region of the helmet-protected head was hit 1 or 3 times. Thirty-one additional tests were conducted with a 100-g impactor. Diffuse axonal injury in distant regions of the brain was assessed with immunohistochemistry for NF-200, the heaviest neurofilament subunit, and glial fibrillary acidic protein, an intermediate filament protein in astrocytes. Hemorrhages were analyzed by unspecific peroxidase. There were 10 controls. A single impact at 7.4 and 9.3 m/s velocity with the 50-g impactor causes minimal neuronal injury and astrocytosis. Repeat impacts with 11.2 m/s velocity and more than 9.3-m/s impacts with 100 g cause diffuse axonal injury and distant injury bilaterally in the cerebral cortex, the subcortical, the white matter, the hippocampus CA1, the corpus callosum, and the striatum, as indicated by NF-200 accumulation in neuronal perikarya 10 days after impact. It also causes reactive astrocytosis in the midline regions of the cerebral cortex and periventricularly. Regions with erythrocyte-loaded blood capillaries indicated brain edema in regions of the cerebral cortex, the brainstem, and the cerebellum. When the immunohistochemical results are extrapolated to professional football players, concussions result in no or minimal brain injury. Repeat impacts at higher velocity or with a heavier mass impactor cause extensive and distant diffuse axonal injury. Based on this model, the threshold for diffuse axonal injury is above even the most severe conditions for National Football League concussion.Neurosurgery 07/2009; 64(6):1174-82; discussion 1182. · 2.79 Impact Factor -
Article: Low-level blasts raise intracranial pressure and impair cognitive function in rats.
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ABSTRACT: Brain injury after high-level blast has been established both clinically and experimentally. Less is known about the effects on the brain of exposure to low to moderate blast levels, such as those encountered by military personnel during the firing of weapons. This study investigates if exposure to occupational levels of low-level blasts affect intracranial pressure and cognitive performance. Rats were exposed to blast overpressure in a shock tube at peak levels of 10, 30, and 60 kPa. Intracranial pressure (ICP) was measured after 0.5, 3, 6, and 10 h and 1, 2, 3, 5, and 7 days. We found two features of the response: a dose-dependent rise in ICP in rats exposed to blast, and an increasing time delay in elevation with decreasing intensity of exposure. The ICP increased in a dose-dependent fashion, up to 15.7 mm Hg after exposure to a 60-kPa blast from a control level of 6 mm Hg. While the initial elevation took place within 30 min after exposure to 60 kPa, it did not appear until after 2 and 6 h for 30 and 10 kPa, respectively. In all cases, the ICP returned to control levels after 7 days. The cognitive function of the blast-exposed rats was assessed with the Morris water maze. After exposure to 10 or 30 kPa and re-testing 2 days later, the latency was increased by over 100%. The results show that exposure of rats to blast levels as low as 10 kPa affects both ICP and cognitive function. Though species differences do not allow direct extrapolation to humans, these findings do pose the question as to whether the thresholds for brain injury might be lower than those of other organs used to set training standards for blast exposure.Journal of neurotrauma 04/2009; 26(8):1345-52. · 4.25 Impact Factor -
Article: Neuropathology and pressure in the pig brain resulting from low-impulse noise exposure.
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ABSTRACT: Military personnel are exposed to occupational levels of blast overpressure during training. This study characterizes the pressure-time histories of air, underwater, and localized blast, and correlates blast parameters with neuropathology. Blast overpressure was produced by a howitzer, a bazooka, an automatic rifle, underwater explosives, or a shock tube. Anesthetized pigs were exposed in positions that simulated real training scenarios. Underwater exposures were performed using explosives at distances recommended by safety requirements. In other experiments, rats were exposed via a shock tube. The pressure changes were recorded with a hydrophone sensor in the brain of the pig and in rats with an optical fiber sensor. Histological examination of porcine brains revealed small parenchymal and subarachnoid hemorrhages, predominately in the occipital lobe, cerebellum, and medulla oblongata. Relative to the peak pressure in air, that in porcine brain (Pmax brain/air) was 0.7 for the bazooka and 0.5 and 0.7, respectively, for the 9- and 30-kPa howitzer. The attenuation was stronger in water: the detonation pulse had a brain/water ratio of 0.1, and the secondary pulses had ratios of 0.3-0.4. The results indicate that low-frequency spectra penetrate easily from air or water into the brain, but high-frequency spectra appear to be filtered by body structures. In addition, blast waves were recorded in the brain and abdomen of pigs after local exposure via shock tube to either the abdomen or the top of the skull. When the abdomen was exposed, the maximal peak value in the brain was only 3% of that in the abdomen. Moreover, part of this pressure could have been derived from the air outside the head. The results gave little support to significant transmission of pressure within the body.Journal of Neurotrauma 02/2009; 25(12):1397-406. · 3.65 Impact Factor -
Article: Impulse noise transiently increased the permeability of nerve and glial cell membranes, an effect accentuated by a recent brain injury.
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ABSTRACT: A single exposure to intense impulse noise may cause diffuse brain injury, revealed by increased expression of immediate early gene products, transiently altered distribution of neurofilaments, accumulation of beta-amyloid precursor protein, apoptosis, and gliosis. Neither hemorrage nor any gross structural damage are seen. The present study focused on whether impulse noise exposure increased the permeability of nerve and glial cell membranes to proteins. Also, we investigated whether a preceding, minor focal surgical brain lesion accentuated the leakage of cytosolic proteins. Anaesthetized rats were exposed to a single impulse noise at either 199 or 202 dB for 2 milliseconds. Transiently elevated levels of the cellular protein neuron specific enolase (NSE) and the glial cytoplasmic protein S-100 were recorded in the cerebrospinal fluid (CSF) during the first hours after the exposure to 202 dB. A surgical brain injury, induced the day before the exposure to the impulse noise, was associated with significantly increased concentrations of both markers in the CSF. It is concluded that intense impulse noise damages both nerve and glial cells, an effect aggravated by a preexisting surgical lesion. The impulse of the shock wave, i.e. the pressure integrated over time, is likely to be the injurious mechanism. The abnormal membrane permeability and the associated cytoskeletal changes may initiate events, which eventually result in a progressive diffuse brain injury.Journal of Neurotrauma 09/2003; 20(8):787-94. · 3.65 Impact Factor -
Article: Exposure to short-lasting impulse noise causes neuronal c-Jun expression and induction of apoptosis in the adult rat brain.
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ABSTRACT: Exposure to impulse noise, above a certain intensity, is harmful to auditory function. Effects of impulse noise on the central nervous system (CNS) are largely unexplored, and there is little information on critical threshold values and time factors. We have recently shown that neurofilament proteins are affected in the cerebral cortex and the hippocampus. Now we show that impulse noise induces expression of the immediate early gene c-Jun products, proposed to play a role in the initiation of neuronal death, and apoptosis as revealed by TUNEL staining. Rat brains were investigated immunohistochemically 2 h to 21 days after exposure to impulse noise of 198 dB or 202 dB. c-Jun was expressed in neuronal perikarya in layers II-VI of the temporal cortex, the cingulate and the piriform cortices at 2 h to 21 days after both exposure levels. Granule neurons of the dentate gyrus and the CA1-3 in the hippocampus pyramidal neurons were similarly affected. The elevated expression of c-Jun products remained high at all postexposure times. TUNEL staining was positive among the same nerve cell populations 6 h after exposure and persisted even at 7 days at both exposure levels.Journal of Neurotrauma 09/2002; 19(8):985-91. · 3.65 Impact Factor -
Article: Expression of c-Fos and c-Myc and deposition of beta-APP in neurons in the adult rat brain as a result of exposure to short-lasting impulse noise.
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ABSTRACT: There is increasing evidence that impulse noise causes brain damage, but little is known about the mechanisms and extent of the response. Here, rat brains were investigated immunohistochemically for the expression of c-Fos, c-Myc, and beta-APP during the first 3 weeks postexposure to impulse noise of 198 or 202 dB. The expression of c-Fos and c-Myc increased at 2 h after exposure in neurons of the cerebral cortex, thalamus, and hippocampus, and this c-Fos immunoreactivity remained elevated for the entire observation period. The c-Myc immunoreactivity peaked at 18 h in both neurons and astrocytes but returned to control levels at 7 days. Abnormal deposition of beta-APP was evident within 6 h in the same brain regions. The beta-APP immunoreactivity was most prominent at 18 h and remained increased over the 21-day period assessed. The observed effects were similar to those described in humans following traumatic brain injury and in Alzheimer's disease. We conclude that impulse noise influences the brain in a fashion similar to that in cases with progressive CNS degeneration.Journal of Neurotrauma 04/2002; 19(3):379-85. · 3.65 Impact Factor -
Article: Exposure to short-lasting impulse noise causes microglial and astroglial cell activation in the adult rat brain.
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ABSTRACT: Exposure to impulse noise, i.e. pressure waves, is above a certain intensity, harmful to auditory function. Intense, short-lasting impulse noise of 198 or 202 dB affects the heavy subunit of neurofilament proteins in neuronal perikarya of the cerebral cortex and hippocampus. There was as well an increased expression of immediate early gene products and induction of neuronal apoptosis. Here, we show that this range of exposure also affects glial cells. We identified microglial cells with an antibody against the complement receptor type 3 (OX-42) and astrocytes with an antibody against the glial fibrillary acidic protein (GFAP). The pattern of damage included microglial activation as early as 2 h after exposure to 202 dB. The activation increased further at 18 h. There was a significant increase of the area occupied by microglial cells in the anterior and posterior hypothalamus and in the lateral septal nucleus. Astrogliosis was observed in the cerebral cortex, the dentate gyrus and in the pyramidal cell layers as well as in white matter of the hippocampus. Both the microglial and astrocytic reactivities remained at 21 days. Exposure to 198 dB, caused similar, but less prominent activation in both cell types.Pathophysiology 01/2002; 8(2):105-111. -
Article: A new approach for multiple sampling of cisternal cerebrospinal fluid in rodents with minimal trauma and inflammation
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ABSTRACT: A new approach was developed to minimize inevitable damage to nervous and meningeal tissue due to implantation of a sampling tube allowing multiple withdrawal of cerebrospinal fluid (CSF) from the cisterna magna in adult rats. A tube was secured on the atlanto-occipital membrane. Thereafter, a hole was cut through the membrane, allowing flow of CSF from the cisterna magna to the tube, CSF could be sampled repeatedly for at least 1 week. There was no blood-brain barrier damage. The pressure in the cisterna magna remained normal as did the estimated rate of CSF formation. Very few blood cells contaminated the CSF. There was very little evidence of inflammation. The nervous tissue was undamaged as shown by exclusion of a dye-protein complex. The CSF concentrations of the cytosolic neuronal protein neuron-specific enolase (NSE), and of the astrocyte protein S-100 were very low. The pattern of amino acids remained within normal limits. Scanning electron microscopy revealed that clot and reactive changes were restricted to the vicinity of the connecting hole. We conclude that our approach to positioning a tube on the atlanto-occipital membrane and then connecting it to the cisterna magna reproducibly and reliably enables ‘atraumatic’ multiple sampling of CSF.Journal of Neuroscience Methods.
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2002–2011
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University of Gothenburg
- Department of Medical Biochemistry and Cell Biology
Göteborg, Vaestra Goetaland, Sweden
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