Biomedical subjects

A Suneson

Publications and source records attributed to A Suneson.

At least 19 recordsLinked to original sources

PubMed2006

Differential gene expression in the rat cochlea after exposure to impulse noise.

Understanding the molecular biology of noise trauma is vital to developing effective and timely interventions. In a model of explosion-mediated impulse noise injury, differential gene expression was studied in whole rat cochlea preparations at 3 and 24 h following the exposure. We developed a technique using mRNA from a single cochlea on each oligonucleotide microarray to avoid pooling of mRNA samples. Application of a conservative statistical analysis approach resulted in the identification of 61 differentially expressed genes. Within 3 h after the exposure, there was an up-regulation of immediate early genes, mainly transcription factors and genes involved in the tissue's response to oxidative stress. No genes were found to be significantly down-regulated. At 24 h following the exposure, up-regulated genes included members of inflammatory and antioxidant pathways and one gene involved in glutathione metabolism was down-regulated. A subset of genes was confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The present study demonstrates the power of the microarray technique in providing a global view of the gene regulation following noise exposure, and in identifying genes that may be mechanistically important in hearing loss, and thereby serve as a basis for the development of therapeutic interventions.

Acoustic Stimulation↗

PubMed2005

Beneficial effects of hypertonic saline/dextran on early survival in porcine endotoxin shock.

BACKGROUND: Hypertonic saline/dextran (HSD) has been shown to have beneficial effects in haemorrhagic shock. These effects, with improved haemodynamics and organ perfusion, would in theory also be of benefit in septic shock. However, this is less studied. We have therefore further evaluated the effect of additional treatment with HSD in a porcine endotoxin shock model. METHODS: Sixteen anaesthetized pigs were used. A continuous infusion of endotoxin (LPS EC) was increased stepwise during 30 min to a rate of 5 microg/kg/h. The infusion was discontinued after 3 h and the animals were observed for another 2 h. The animals received continuous basal fluid resuscitation with isotonic Ringer's glucose 2.5% at a rate of 20 ml/kg/h throughout the experiment. After 1 h of endotoxin infusion, the animals were randomized to additional treatment with HSD, 4 ml/kg over 5 min, or the same volume of isotonic saline. Every 30 min, haemodynamics and mixed venous saturation (SvO2) were measured via a pulmonary artery catheter. Regional blood flow rates were measured continuously by perivascular ultrasonic flow probes. The metabolic response was measured by arterial blood gas analysis. RESULTS: The endotoxin put all animals into a progressive hypodynamic circulatory shock during the experiment. Treatment with HSD improved survival rate to 8/8 compared with controls 3/8. There was a transient circulatory recovery with improved central and regional haemodynamics, accompanied by stabilized metabolic response. CONCLUSION: Treatment with additional HSD improves survival in an early phase of endotoxin shock. Generally improved haemodynamics and oxygenation of peripheral tissues are suggested as possible mechanisms.

Analysis of Variance↗

PubMed2004

Semaphorin and neuropilin expression in motoneurons after intraspinal motoneuron axotomy.

We have examined mRNA and protein distribution for the axon guidance molecules semaphorin3A, 3F, 4F and semaphorin receptors neuropilin-1 and 2, 1-21 days after intramedullary axotomy of rat lumbar spinal cord motoneurons. We show that semaphorin3A mRNA and protein are up-regulated in the scar and in motoneurons from 3 days and upto 3 weeks after injury. Neuropilin-1 mRNA showed no changed expression in axotomized motoneurons. Semaphorin3F mRNA expression was found in ventral roots after ventral funiculus lesion (VFL) and neuropilin-2 mRNA was found in affected motoneurons from 1 day after injury throughout the examined period. Semaphorin4F mRNA was first found in motoneurons 3 weeks after lesion. These results suggest semaphorin/neuropilin involvement in the injury response of intramedullary axotomized motoneurons.

Animals↗

PubMed2001

Early resuscitation with hypertonic saline/dextran in uncontrolled intra-abdominal bleeding in swine combined with a soft tissue gunshot wound.

The effects of hypertonic saline/dextran (HSD) on hemodynamics and on rebleeding were studied during an uncontrolled intra-abdominal hemorrhage combined with a high-energy gunshot wound (GSW) in the hind limb of anesthetized swine. The GSW had instant effects on the central hemodynamics, which were aggravated when the internal hemorrhage was induced. Compared with baseline, cardiac output decreased to about 42%, mean arterial pressure decreased to 52 +/- 4%, and mean flow rates in the splanchnic region, in the upper aorta, and in the kidney decreased to 51 to 15%. The injection of HSD at 10 minutes was followed by a prompt increase in blood flow rates, but rebleeding occurred in five of eight animals, although only two died. In conclusion, GSW induced instant changes in hemodynamics at distance from the injury. When HSD treatment was given in a bolus injection, rebleeding occurred in five of eight animals, although the second hemorrhage became fatal in only one animal.

Animals↗

PubMed2000

Neck injuries in car collisions--a review covering a possible injury mechanism and the development of a new rear-impact dummy.

A review of a few Swedish research projects on soft tissue neck injuries in car collisions is presented together with some new results. Efforts to determine neck injury mechanisms was based on a hypothesis stating that injuries to the nerve root region in the cervical spine are a result of transient pressure gradients in the spinal canal during rapid neck bending. In experimental neck trauma research on animals, pressure gradients were observed and indications of nerve cell membrane dysfunction were found in the cervical spinal ganglia. The experiments covered neck extension, flexion and lateral bending. A theoretical model in which fluid flow was predicted to cause the transient pressure gradients was developed and a neck injury criterion based on Navier-Stokes Equations was applied on the flow model. The theory behind the Neck Injury Criterion indicates that the neck injury occurs early on in the rearward motion of the head relative to the torso in a rear-end collision. Thus the relative horizontal acceleration and velocity between the head and the torso should be restricted during the early head-neck motion to avoid neck injury. A Bio-fidelic Rear Impact Dummy (BioRID) was developed in several steps and validated against volunteer test results. The new dummy was partly based on the Hybrid III dummy. It had a new articulated spine with curvature and range of motion resembling that of a human being. A new crash dummy and a neck injury criterion will be very important components in a future rear-impact crash test procedure.

Accidents, Traffic↗

PubMed2000

Induction of VEGF and VEGF receptors in the spinal cord after mechanical spinal injury and prostaglandin administration.

Vascular endothelial growth factor (VEGF) is an angiogenetic factor that promotes endothelial cell proliferation during development and after injury to various types of tissue, including the central nervous system (CNS). Using immunohistochemical and in situ hybridization methods we have here demonstrated that VEGF and its receptors Flk-1, Flt-1 and Neuropilin-1 mRNAs and proteins are induced after incisions in the rat spinal cord. The inducible enzyme for prostaglandin synthesis cyclooxygenase-2 (COX-2) is known to be upregulated after spinal injury, cerebral ischemia and to stimulate angiogenesis. To test the hypothesis that prostaglandins may be involved in the VEGF response after lesion we investigated whether intraspinal microinjections of prostaglandin F2alpha (PGF2alpha) alters VEGF expression in the spinal cord. Such treatment was followed by a strong upregulation of VEGF mRNA and protein in the injection area. Finally, by use of an in vitro model with cell cultures of meningeal fibroblast and astrocyte origin, resembling the lesion area cellular content after spinal cord injury but devoid of inflammatory cells, we showed that VEGF is expressed in this in vitro model cell system after treatment with PGF2alpha and prostaglandin E2 (PGE2). These data suggest that cells within a lesion area in the spinal cord are capable of expressing VEGF and its receptors in response to mechanical injury and that prostaglandins may induce VEGF expression in such cells, even in the absence of inflammatory cells.

Animals↗

PubMed2000

Physiological changes in pigs exposed to a blast wave from a detonating high-explosive charge.

The aim of this project was to study respiration, circulation, and brain activity in pigs during and after a blast wave exposure. Ten anesthetized pigs were used. Seven were exposed to blast and three were controls. Physiological parameters of respiration and circulation as well as cortical activity were followed from 30 minutes before until 120 minutes after the real or simulated blast. There were no significant changes in heart rhythm, cardiac output, arterial oxygen or carbon dioxide tension, blood pH, or mixed venous saturation during the experiment. The blast exposure caused intestinal injuries but no lung damage. A transient flattening of the electroencephalogram was seen immediately after the blast in four experimental animals, in contrast to the unchanged baseline electroencephalogram of the control animals. This momentary depression of cortical activity accompanied by short-lasting apnea indicates a blast wave-induced effect on the brainstem or higher controlling center.

Animals↗

PubMed1999

A placebo-controlled experimental study of steroid inhalation therapy in ammonia-induced lung injury.

BACKGROUND: The use of corticosteroids in toxic lung injury caused by exposure to an irritating gas such as ammonia has not been adequately studied. OBJECTIVE: To evaluate the effects of budesonide inhalation in a rabbit model of toxic lung injury induced by ammonia. DESIGN: Randomized, blind placebo-controlled laboratory investigation employing 16 New Zealand White rabbits. Lung injury was induced by inhalation of a defined amount of aerosolized ammonia. Thirty minutes later, the rabbits were randomized to receive either inhalation therapy with 0.5 mg budesonide or placebo. After another 2 hours, a second treatment inhalation, identical to the first one, was administered. RESULTS: Airway pressures, hemodynamics, and gas exchange were measured at baseline, 5, and 15 minutes after ammonia administration and every 30 minutes during a 6-hour period after the first blind inhalation of corticosteroids or placebo. The ammonia inhalation resulted in an acute severe lung injury, detected after 15 minutes as a decrease in Pao2 from 23.3 (+/- 3.6) to 11.0 (+/- 3.6) kPa (p < 0.005) and an increase in peak airway pressure from 13 (+/- 2) to 17 (+/- 2) cm H2O (p < 0.005). During the 6-hour observation period, the blood gas parameters improved gradually in all rabbits. In comparison with placebo, budesonide did not result in improved gas exchange or reduced airway pressure levels during the observation period. CONCLUSION: In this animal model corticosteroid inhalation therapy had no effect on ammonia-induced lung injury.

Administration, Inhalation↗

PubMed1999

Microvascular lung tissue oxygenation--a methodological study in the pig.

The objective of the present study was to investigate the possibility of measuring lung tissue oxygen pressure (PtO2) distributions at the microvascular level, and also if a change in the lung tissue oxygenation could be detected during hypoventilation (50% reduction in ventilatory settings). Experiments were carried out on eight mechanically ventilated ketamine-anaesthetised pigs. A thoracotomy was performed through the third right intercostal space. PtO2 measurements were made using a Clark-type multiwire microelectrode placed onto the pleural surface of the middle lobe. PtO2 was measured during normoventilation, hypoventilation (3 minutes) (reduction of respiratory volume/minute and frequency by 50%), and a second period of normoventilation. Baseline PtO2 was 5.8 (range 4.4 to 10.3) kPa and decreased to 2.9 (range 1.6 to 4.2) kPa during hypoventilation, associated with some PtO2 values close to zero. The PtO2 increased to 5.4 (range 3.6 to 8.4) kPa during the second normoventilatory period, some values still close to zero. This study demonstrates that lung tissue PO2 registrations can be made in a suitable animal (pig) model, and that hypoventilation induced an almost reversible decrease in lung tissue oxygen pressure distributions. In addition, no microscopically visible tissue damage was inflicted by the electrode on the underlying lung surface.

Animals↗

PubMed1998

Acoustic trauma causes reversible stiffness changes in auditory sensory cells.

A common cause of hearing impairment is exposure to loud noise. Recent research has demonstrated that the auditory mechanosensory cells are essential for normal hearing sensitivity and frequency selectivity. However, little is known about the effect of noise exposure on the mechanical properties of the auditory sensory cells. Here we report a significant reduction in the stiffness and cell length of the outer hair cells after impulse noise exposure, suggesting that mechanical changes at the cellular level are involved in noise-induced hearing loss. There is a recovery of the cellular stiffness and cell length over a two-week period, indicating an activation of cellular repair mechanisms for restoring the auditory function following noise trauma. The reduced stiffness observed at the cellular level is likely to be the cause for the downward shift of the characteristic frequency seen following acoustic trauma. The deterioration and the recovery of the mechanical properties of outer hair cells may form important underlying factors in all kinds of noise-induced hearing loss.

Animals↗

PubMed1998

Central and regional hemodynamics during uncontrolled bleeding using hypertonic saline dextran for resuscitation.

The effects of hypertonic (7.5%) saline/6% dextran 70 (HSD) on central and regional hemodynamics were studied during uncontrolled intra-abdominal bleeding in 16 anesthetized pigs. Ultrasonic flow probes were placed proximally and distally to an aortic injury to indicate the incidence and extent of rebleeding after injecting 4 mL kg(-1) (N = 8) and 2.65 mL kg(-1) (N = 8) of HSD 10 min after the vascular injury was induced. The initial aortic bleeding reduced the blood flow rates to 71% of baseline in the skin, 53% in the splanchnic region, 42% in the upper aorta, and 15% in the kidney. Cardiac output dropped to 46% and the mean arterial pressure to 57% of baseline. The injection of HSD was followed by a prompt increase in all blood flow rates, but rebleeding started within 2 min in 13 of the pigs (81%). A second period of rebleeding occurred in six of them. The rebleeding averaged 300 mL, which is 62% of the blood lost when the aortic injury was induced. There was no significant difference between the treatment groups with respect to these blood losses or to the oxygen consumption, which was not restored by HSD. Five animals in each treatment group died after about 70 min, while the remaining six pigs (38%) survived the 120 min study period. These results suggest that HSD in the recommended dose, and even two-thirds thereof, promotes rebleeding when given shortly after a low energy intra-abdominal aortic injury. The fluid seems to have no beneficial effect on this type of uncontrolled hemorrhage.

Animals↗

PubMed1998

[Nerve cell damages in whiplash injuries. Animal experimental studies].

Mechanical loading of the cervical spine during car accidents often lead to a number of neck injury symptoms with the common term Whiplash Associated Disorders (WAD). Several of these symptoms could possibly be explained by injuries to the cervical spinal nerve root region. It was hypothesised that the changes in the inner volume of the cervical spinal canal during neck extension-flexion motion would cause transient pressure changes in the CNS as a result of hydro-dynamic effects, and thereby mechanically load the nerve roots and cause tissue damage. To test the hypothesis, anaesthetised pigs were exposed to experimental neck trauma in the extension, flexion and lateral flexion modes. The severity of the trauma was kept below the level where cervical fractures occur. Transient pressure pulses in the cervical spinal canal were duly recorded. Signs of cell membrane dysfunction were found in the nerve cell bodies of the cervical spinal ganglia. Ganglion injuries may explain some of the symptoms associated with soft-tissue neck injuries in car accidents. When the pig's head was pulled rearward relative to its torso to resemble a rear-end collision situation, it was found that ganglion injuries occurred very early on in the neck motion, at the stage where the motion changes from retraction to extension motion. Ganglion injuries did not occur when pigs were exposed to similar static loading of the neck. This indicates that these injuries are a result of dynamic phenomena and thereby further supports the pressure hypothesis. A Neck Injury Criterion (NIC) based on a theoretical model of the pressure effects was developed. It indicated that it was the differential horizontal acceleration and velocity between the head and the upper torso at the point of maximum neck retraction that determined the risk of ganglion injuries.

Animals↗

PubMed1997

Effects of peripheral high energy missile trauma on the oxygenation of lung tissue in the pig.

The purpose of this paper was to study the effect of peripheral high energy missile trauma on oxygenation of the lung tissue. Eleven pigs were randomised to either high energy gunshot wound of the soft tissues of the thigh or sham exposure. Under anaesthesia and controlled ventilation, the carotid artery and the jugular vein were catheterised and a thoracotomy was performed. A Clark-type multiwire electrode was placed on the surface of the middle lung lobe for registration of the oxygen pressure fields of the lung tissue (PtO2). In animals subjected to missile trauma, an increased heterogeneity was seen in PtO2 1 and 2 hours after exposure, specially under hypoventilatory provocation. Furthermore, PtO2 values did not return to baseline when hypoventilation was followed by normoventilation, in contrast to what was seen in the sham exposed animals. No differences between groups were found in arterial PO2, O2-saturation, PCO2, pH or in pulse frequency. These findings of disturbance in oxygenation of pulmonary tissue, may represent an early phase in the development of a lung injury resembling the post-traumatic adult respiratory distress syndrome seen in man. The initiating events could be release of mediators from traumatised tissue and/or direct effects of the shock waves from missile impact, passing through the body.

Animals↗

PubMed1996

Comparison among different approaches for sampling cerebrospinal fluid in rats.

Two approaches for time-resolved sampling of cerebrospinal fluid (CSF) in rats were compared regarding performance, reproducibility, and extent of the inevitable trauma caused by the implantation of a sampling tube. Several parameters were checked to evaluate the injury: blood cell contamination of CSF; concentrations in CSF of the cytosolic proteins neuron-specific enolase (NSE) and S-100 (chiefly present in astrocytes); blood-brain barrier leakage of a dye-protein complex; viability of nervous tissue cells as assessed by dye exclusion; light and electron microscopy. In one sampling method, a tube was forced epidurally into the cisterna magna via a hole in the calvarium, consistently damaging the meninges and the nervous tissue. When using the alternative sampling method, the tube was instead affixed to the posterior atlanto-occipital membrane and connected with the cisterna magna via a hole in the membrane. Such a procedure caused negligible damage. Both techniques induced an inflammatory response. We advocate the use of the second approach, i.e., to sample CSF via a hole in the atlanto-occipital membrane, as the method of choice due to its high reproducibility. It is fairly rapid, and associated with a negligible injury.

Animals↗

PubMed1996

Membrane leakage in spinal ganglion nerve cells induced by experimental whiplash extension motion: a study in pigs.

Nerve cells in the cervical and upper thoracic spinal ganglia were examined for possible plasma membrane leakage, as revealed by their ability to exclude a dye-protein complex, after experimentally induced whiplash in a pig model system. The rationale for this approach is found in the fact that the interstitium of spinal ganglia differs from most other parts of the nervous system in that it lacks a barrier, allowing blood constituents to gain access. The dye Evans blue, which rapidly conjugates with blood proteins, is found in the interstitium of normal spinal ganglia after intravenous injection, but it is excluded from the nerve cells and their enveloping satellite cells. In contrast, after a simulated whiplash extension trauma many of the nerve cells were stained, reflecting the inability of their plasma membranes to exclude the dye-protein complex. Morphometric measurements revealed that the highest frequency of cellular dye uptake was observed in the C4-C7 spinal ganglia (mean 16 - 18%; range 5-27%). The blood-nerve barrier of the adjacent nerve fascicles remained intact, with rare exception. Several factors are considered to contribute to the induction of these cell abnormalities in the spinal ganglia after an experimentally induced, simulated whiplash trauma in this pig model system.

Animals↗

PubMed1995

A new approach for multiple sampling of cisternal cerebrospinal fluid in rodents with minimal trauma and inflammation.

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.

Amino Acids↗

PubMed1990

Pressure wave injuries to the nervous system caused by high-energy missile extremity impact: Part I. Local and distant effects on the peripheral nervous system--a light and electron microscopic study on pigs.

Pigs were used for studies of effects on the peripheral nervous tissue of pressure waves induced by impact and passage through the left thigh of high-energy missiles. The short-lasting pressure waves were demonstrated to move close to the speed of sound and to have a spectrum of high frequencies and large amplitudes. The sciatic nerve in the contralateral leg showed no hemorrhage or major deformation. Both immediately after the missile impact and after 48 hr the myelin sheaths in the contralateral sciatic nerve showed deformation. Myelin was bulging into the axon, dislocating the axoplasm. The nodes of Ranvier could be exposed to an increased extent. Electron microscopic examination revealed decreased number of microtubules immediately after the trauma, persisting even after 48 hr in the largest axon. Schwann cells showed, especially after 48 hr, signs of damage and swelling. Similar changes, although less extensive, were noticed in the phrenic nerves as well as in unmyelinated axons in both sciatic and phrenic nerves. It is concluded that a high-energy missile hit in the thigh of a pig, caused structurally demonstrable dislocations of myelin sheaths, and disarrangement of cytoskeleton and endoplasmic reticulum in axons as well as other signs of damage. The changes may interfere with the normal functions of peripheral and autonomic nerves.

Abdomen↗

PubMed1990

Pressure wave injuries to the nervous system caused by high-energy missile extremity impact: Part II. Distant effects on the central nervous system--a light and electron microscopic study on pigs.

The aim of the present study was to investigate if distant effects could be detected within the central nervous system after impact of a high-energy missile in the left thigh of young pigs. Pressure transducers implanted in various parts of the body of the animal, including the brain, recorded a short-lasting burst of oscillating pressure waves with high frequencies and large amplitudes, traversing the body tissue with a velocity of about that of sound in water (1,460 m/s). The distance between the point of impact and the brain and cervical spinal cord is in the range of 0.5 m. Macroscopic examination revealed that there was no gross brain tissue disruption or visible blood-brain barrier dysfunction. Light microscopic examination demonstrated myelin invaginations in the largest axons and shrinkage of axoplasm. Electron microscopic examination revealed a reduction in the number of microtubules, especially in the larger axons in the brainstem. Disintegration of Nissl substance, i.e., chromatolysis, was noticed after 48 hr in many Purkinje nerve cells in the cerebellum, concomitantly with the appearance of an increased frequency of association between lamellar bodies and mitochondria. Changes could also be observed in the cervical spinal cord and, at reduced frequency and extent, in the optic nerve and in other parts of the brain. These effects were evident within a few minutes after the trauma and persisted even 48 hr after the extremity injury. It is concluded that distant effects, likely to be caused by the oscillating high-frequency pressure waves, appear in the central nervous system after a high-energy missile extremity impact.

Abdomen↗