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Y Olsson

Publications and source records attributed to Y Olsson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Improved recovery after spinal cord trauma in ICAM-1 and P-selectin knockout mice.

Traumatic spinal cord injury is followed by infiltration of leukocytes, influenced by endothelial adhesion molecules such as ICAM-1 and P-selectin. In order to evaluate the pathogenetical role of these molecules, wild-type mice and mice lacking ICAM-1 and P-selectin were subjected to an experimental spinal cord compression of two degrees of severity. Hind limb motor function decreased after injury in all animals but the groups of injured ICAM-1/P-selectin knockout animals had a better functional outcome during the entire observation period of 14 days. This difference was statistically significant on day 1. Our results indicate that adhesion molecules influence the functional outcome after spinal cord injury in a negative way and may be a target for future therapy of neurotrauma.

Animals↗
PubMed1999

Expression of transforming growth factor-beta1, 2, 3 isoforms and type I and II receptors in acute focal cerebral ischemia: an immunohistochemical study in rat after transient and permanent occlusion of middle cerebral artery.

Transforming growth factor beta (TGF-beta) is involved in the modulation of cell growth, differentiation and repair following injury of various organs. Previous studies on human autopsy material have indicated that TGF-beta isoforms-beta1, -beta2 and -beta3, and TGF-beta receptor type I are expressed in various cells of necrotizing brain lesions like infarction and abscess. The present immunohistochemical study was designed to investigate changes that may occur with regard to TGF-beta and its receptors type I and II in a rat model of focal brain ischemia induced by transient or permanent occlusion of the middle cerebral artery. Our findings indicate that at days 1 and 3 following such transient and permanent ischemia there is an up-regulation of TGF-beta isoforms -beta1, -beta2 and -beta3, and TGF-beta receptor types I and II mainly in the perifocal neurons, reactive astroglial cells, endothelial cells and macrophages.

Animals↗
PubMed1999

Systemic hypothermia following compression injury of rat spinal cord: reduction of plasma protein extravasation demonstrated by immunohistochemistry.

Systemic hypothermia has neuroprotective effects in experimental models of central nervous system ischemia caused by vascular occlusions. The present study addresses the question as to whether systemic hypothermia can influence the extravasation of plasma proteins following severe spinal cord compression trauma using immunohistochemistry to identify the plasma proteins albumin, fibrinogen and fibronectin. Fifteen rats were assigned to one of three groups and received either thoracic (T) laminectomy or severe spinal cord compression trauma of the T8-9 segment. One group comprised laminectomized animals without compression trauma submitted to a hypothermic procedure in which the core temperature was reduced from 38 degrees to 30 degrees C. The two trauma groups were either submitted to the same hypothermic procedure or kept normothermic during the corresponding time. All animals were killed 24 h following the surgical procedure. The normothermic and hypothermic trauma groups had indications of marked extravasation of albumin, fibrinogen and fibronectin at the site of the injury (T8-9). There was also pronounced extravasation in the cranial and caudal peri-injury zones (T7 and T10) of normothermic injured rats but, with few exceptions, not in the hypothermic ones with the same degree of compression. By measuring the cross-sectional area of the peri-injury zones we found in the hypothermic trauma group a significant reduction of the expansion compared with that present in normothermic injured rats. Our study thus indicates that hypothermia reduces the extravasation of the plasma proteins albumin, fibrinogen and fibronectin following spinal cord compression in the rat. Such a reduction may contribute to neuroprotective effects exerted by hypothermia.

Animals↗
PubMed1999

Clomethiazole (ZENDRA, CMZ) improves hind limb motor function and reduces neuronal damage after severe spinal cord injury in rat.

Clomethiazole (CMZ) has a neuroprotective effect in experimental focal and global forebrain ischemia. This neuroprotective effect may depend on its ability to enhance GABA receptor activity. We have studied the effect of pretreatment with CMZ on motor function recovery and nerve cell damage after spinal cord injury (SCI). Rats were randomized and 30 min before SCI they received a single intraperitoneal dose of CMZ (150 mg/kg) or saline. The spinal cord was injured with a 50 g (4.5 g/mm2) load, applied over the exposed dura, through a curved rectangular plate (2.2 x 5.0 mm) for 5 min at T8-9. The animals became paraplegic 1 day after injury. The rats were evaluated for recovery of hind limb motor function. All animals recovered to some extent over the observation period of 12 weeks. However, hind limb motor function was significantly better in the animals pretreated with CMZ. At 12 weeks the rats were killed and perfused/fixed for morphological investigations. Microtubule-associated protein 2 (MAP2) immunostaining was used to stain neurons and dendrites and Luxol-fast blue to stain myelinated tracts of the white matter. The injured segment of the spinal cord showed severe atrophy, distortion, cavitation and necrosis of grey and white matter. Compared to uninjured controls the transverse sectional area was reduced to 32.7 +/- 4% in untreated animals but only to 38.5% +/- 4.1 in CMZ-treated animals. MAP2 staining showed that, compared to uninjured controls, grey matter was reduced to 7.4 +/- 2.7% in saline-treated injured animals and to 22.7 +/- 5.4% in CMZ-treated rats. Our results thus show that in this model CMZ improves hind limb motor function and attenuates the morphological damage to the spinal cord.

Animals↗
PubMed1999

Apoptosis of oligodendrocytes occurs for long distances away from the primary injury after compression trauma to rat spinal cord.

We evaluated by in situ nick end labeling the presence of apoptotic glial cells in the spinal cord of rats which have sustained a moderate and severe compression injury at the level of T8-9, resulting in a severe but reversible paraparesis and irreversible paraplegia, respectively. In a previous investigation we found apoptotic glial cells (oligodendrocytes) in the immediate vicinity of the primary lesion (T7 and T10). The present study was designed to evaluate the extent of such cells in the spinal cord even at long distances away from the primary injury. Rats sustaining a moderate and severe compression injury and surviving 4 and 9 days showed a significant increase in the number of apoptotic glial cells at the T1, T5, T7, T12 and L2 levels. At the T10 level the elevation was significant only after day 9. There was no significant increase in the number of these cells at 4 h and 1 day after moderate and severe compression. In general, the apoptotic cells were most often seen in segments adjacent to the compression. They were randomly located in the ventral, lateral and dorsal tracts but were rarely present in the gray matter of the cord. In conclusion, compression trauma to rat spinal cord induces signs of apoptosis in glial cells, presumably oligodendrocytes of the long tracts. This newly discovered type of secondary injury is widely distributed in the damaged spinal cord and occurs even at long distances remote from the initial compression injury. Apoptotic cell death of oligodendrocytes will induce myelin degeneration and cause additional disturbances of axonal function. This cell damage may be a target for future therapy since it occurs after a delay and chemical compounds are now available by which apoptotic cell death can be modified.

Amyloid beta-Protein Precursor↗
PubMed1999

Behavioural and morphological outcome of mild cortical contusion trauma of the rat brain: influence of NMDA-receptor blockade.

The authors studied the effect of a mild cortical contusion to the rat brain on behavioural and morphological outcome and the influence of NMDA-receptor blockade (MK-801, 0.5 mg/kg i.v. 30 min prior to trauma). Spontaneous motor activity was assessed 16-18 days post trauma. Saline treated traumatised rats showed a significant (p < 0.01) hyperactive behaviour compared to animals without injury. MK-801 treated rats performed significantly better than the saline treated animals (p < 0.05). For histopathological evaluation hippocampal hilar neurons were counted, cortical thickness under the impact was measured and microtubule-associated protein 2 (MAP2) immunoreactivity in the dentate hilus was quantified 1, 3 and 21 days post trauma. In traumatised rats scattered loss of nerve cells, oedema and minute haemorrhages were present at the site of the impact one and three days after injury. At day 21 there was a significant reduction of cortical thickness at the site of impact. One day after trauma there was a bilateral, significant loss of neurons and MAP2 immunostaining in the dentate hilus of the hippocampus. MK-801 pretreated rats showed similar morphological changes. The disturbed spontaneous motor behaviour may be caused by hippocampal damage and a reduction of somatosensory cortical neurons. NMDA-receptor blockade improved the outcome assessed by the functional tests but failed to influence the morphological changes, suggesting that this behavioural test is a more sensitive indicator of outcome after mild traumatic brain injury (TBI).

Animals↗
PubMed1999

Systemic hypothermia following spinal cord compression injury in the rat: axonal changes studied by beta-APP, ubiquitin, and PGP 9.5 immunohistochemistry.

STUDY DESIGN: Systemic hypothermia exerts neuroprotective effects in experimental ischemic CNS models caused by vascular occlusions. Recent experimental and clinical studies have also demonstrated beneficial effects of hypothermic treatment following brain trauma. OBJECTIVES: The present study addresses the question as to whether systemic hypothermia has similar protective qualities following severe spinal cord compression trauma using beta-APP-, ubiquitin-, and PGP-9.5-immunohistochemistry combined with the ABC complex method as markers to identify axonal changes. METHODS: Fifteen rats were randomized into three equally large groups and sustained to either thoracic laminectomy or to severe spinal cord compression trauma of the Th 8 - 9 segments. The non-trauma group contained laminectomized animals submitted to a hypothermic procedure in which the core temperature was reduced from 38 to 30 degrees C. The two trauma groups were either submitted to the same hypothermic procedure or kept normothermic during the corresponding time. All animals were sacrificed 24 h following the surgical procedure. RESULTS: In the hypothermic non-trauma group no axonal changes were seen. The number of abnormal axons, as indicated by accumulation of immunoreactive material in enlarged axons, was lower in the peri-injury zones of the hypothermic trauma group than in the normothermic trauma group. This difference was most obvious in the cranial peri-injury zones. No differences were seen between the groups in the trauma zones. CONCLUSIONS: This study demonstrates reduced axonal swelling in the peri-injury zones of spinal cord injured rats treated with systemic hypothermia. These changes could either indicate neuroprotective effects of the hypothermic treatment, or be results of reduced axonal transport or protein synthesis. To evaluate the clinical importance of our findings, further studies including reliable outcome measures of the animals must be performed.

Amyloid beta-Protein Precursor↗
PubMed1999

Expression of ICAM-1 and CD11b after experimental spinal cord injury in rats.

We have performed an immunohistochemical study on the expression of the adhesion molecules ICAM-1 and CD11b 1 h to 1 week following a compression injury to the rat spinal cord. The spinal cord of control animals showed ICAM-1 expression in some vessels and in the leptomeninges. Mechanical compression of the spinal cord induced an endothelial upregulation of ICAM-1 that was maximal in rats surviving 1-2 days after injury. This reaction was seen at the center of the lesion as well as in the perifocal zones. Apart from the endothelial upregulation, increased ICAM-1 expression also was found in leptomeningeal and ependymal cells of traumatized animals. In control animals resting microglial cells were moderately CD11b immunoreactive. Trauma induced a rapid microglial upregulation of CD11b in the white matter that was evident even at 1 h after injury. By 1 day to 1 week posttrauma conformational changes consistent with microglial activation, i.e., transformation into phagocytic microglial cells, were seen in the white matter. In the gray matter, CD11b immunohistochemistry revealed massive infiltration of phagocytic microglial cells and macrophages in animals surviving 1 day to 1 week. Intravascular and infiltrating leukocytes were intensely CD11b immunopositive. As reflected by CD11b immunohistochemistry, the maximal infiltration of polymorphonuclear leukocytes occurred at 2 days after the insult. Endothelial upregulation of ICAM-1 facilitates adhesion and extravasation of leukocytes by binding to the counterreceptor CD11b. Knowledge regarding the expression and cellular distribution of such molecules after central nervous system trauma is important since inflammatory mechanisms have been suggested to be involved in secondary neurological damage and thus constitute potential targets of therapy.

Analysis of Variance↗
PubMed1999

Interstitial cells of Cajal in the human fetal small bowel as shown by c-kit immunohistochemistry.

BACKGROUND: Interstitial cells of Cajal (ICCs) express the tyrosine kinase receptor c-kit, which is required for their development and spontaneous pacemaker activity in the bowel. From murine models it has been proposed that ICCs do not develop until after birth, but more recent findings indicate that c-kit is expressed early in the embryonic period. The temporal development of ICCs in the human gut remains unknown. AIM: To investigate ICCs in the human fetal small bowel using c-kit immunohistochemistry. SUBJECTS: Small bowel specimens were obtained at post mortem examination of 16 fetuses and nine neonates, eight of whom were premature, born at gestational ages of 13 to 41 weeks, without gastrointestinal disorders. METHODS: Immunohistochemical analysis was performed on material fixed in formalin and embedded in paraffin. The specimens were exposed to antibodies raised against c-kit (an ICC marker) and neurone specific enolase (a general neuronal marker). The ABC complex method was used to visualise binding of antibodies to the corresponding antigens. RESULTS: c-kit immunoreactive cells were visualised from 13 weeks of gestation. The immunoreactivity was mainly localised in association with the myenteric plexus. From about 17-18 weeks of gestation, the ICCs formed a layer along the myenteric plexus, whereas this layer appeared to be disrupted at 13-16 weeks of gestation. CONCLUSIONS ICCs are c-kit immunoreactive at least from a gestational age of 13 weeks in the human fetal small intestine. From 17-18 weeks of gestation until birth, they form a continuous layer around the myenteric ganglia.

Embryonic and Fetal Development↗
PubMed1999

Expression of bcl-2 in enteric neurons in normal human bowel and Hirschsprung disease.

OBJECTIVE: The bcl-2 protein has the functional role of blocking apoptosis, ie, programmed cell death. This protein is widely expressed in the developing central and peripheral nervous systems. The purpose of this study was to map bcl-2 expression in the human enteric nervous system, as this has not previously been done. METHODS: Rectal specimens were obtained at autopsy of 13 fetuses at 13 to 31 weeks of gestation. Normal colon was also obtained from 5 children and 2 adults, and, in addition, ganglionic and aganglionic bowel resected in 11 patients with Hirschsprung disease was examined. Specimens were fixed in formalin, embedded in paraffin, and analyzed with immunohistochemical methods, using antibodies raised against bcl-2 and neuron-specific enolase (NSE). RESULTS: The bcl-2 protein was expressed in myenteric and submucous ganglion cells in fetuses, children, and adults. Nerve fibers of the enteric plexuses that were bcl-2 immunoreactive were few compared with the number of NSE-immunoreactive nerve fibers. In aganglionic bowel no bcl-2-or NSE-immunoreactive ganglion cells were revealed. Results of NSE immunohistochemistry showed clearly stained hypertrophic nerve bundles, known to be of extrinsic origin, which were only weakly bcl-2 immunoreactive. CONCLUSION: Expression of bcl-2 in enteric ganglion cells of the myenteric and submucous plexuses is displayed in the fetus and during childhood and is also retained in adult bowel. Immunohistochemical analysis of bcl-2 provides a good marker for identification of ganglion cells in Hirschsprung disease and may also be valuable for the diagnosis of disorders characterized by hypoganglionosis or hyperganglionosis.

Aged↗
PubMed1998

Expression of endothelial barrier antigen immunoreactivity in blood vessels following compression trauma to rat spinal cord. Temporal evolution and relation to the degree of the impact.

The endothelial barrier antigen (EBA) recognised by a monoclonal antibody is expressed in rat cerebral microvessels possessing blood-brain barrier properties but only weakly by fenestrated vessels. We have studied the expression of this marker in the spinal cord of control rats and compared the findings with those seen in rats subjected to compression injury at the T8-9 level with a survival period of 4 h, 24 h, 4 days and 9 days. To that end, formalin-fixed paraffin-embedded material was immunostained by the avidin-biotin-peroxidase complex method. Sections from control rats presented a distinct immunostaining at the site of the endothelial cells of almost all microvessels in the grey and white matter of the cord. The anterior and posterior spinal arteries did not show such staining. Neurons and glial cells were unstained. Rats which had survived 4 h after a moderate or severe compression trauma still showed immunoreactivity in intramedullary microvessels at the site of injury. There was a moderate reduction of vascular immunoreactivity at 24 h and a pronounced loss of such reactivity at 4 days after trauma. At 9 days after compression the expression of the endothelial barrier antigen had almost been normalised in the microvessels of the cord. In conclusion, using immunohistochemistry, EBA can be demonstrated in noninjured rat spinal cord microvessels, while the staining disappears at the site of compression trauma to the cord. The EBA marker can be used to indicate sites of vascular injury in spinal cord compression injury. The factors causing the disappearance and restitution of the antigen are unknown.

Animals↗
PubMed1998

Amyloid angiopathy of the human brain: immunohistochemical studies using markers for components of extracellular matrix, smooth muscle actin and endothelial cells.

Cerebral amyloid angiopathies comprise a heterogeneous group of conditions characterised by amyloid deposition in leptomeningeal and cortical vessels. We have studied the deposition of extracellular matrix components in such vessels from controls and ten cases with marked amyloid angiopathy. Arterial vessels which were heavily loaded with amyloid often showed lack of immunostaining to collagen type I, III, V and VI in the amyloid-containing parts of the vessel wall but some immunoreactivity remained in the adventitia. The subintimal region of some arterioles presented a faint staining with collagen V and collagen VI antisera. Immunostaining to collagen IV and laminin revealed normal reactivity in the vascular basal lamina and frequently remaining activity in the media. Immunostaining for actin showed a complete or partial loss of reactivity in the amyloid-containing parts of the media but often there was a thin line of staining at the position of pericytes. The endothelial markers did not reveal any changes compared with controls. In other cerebral microangiopathies, for instance Binswanger's leukoencephalopathy, CADASIL and cases presenting hyalinosis there is a deposition of fibrillary collagens in the wall of afflicted microvessels. Degeneration of smooth muscle cells and absence of marked fibrosis in some of the arterial vessels in cases of amyloid angiopathy may explain why such vessels are susceptible to ruptures and haemorrhages.

Actins↗
PubMed1998

Systemic hypothermia after spinal cord compression injury in the rat: does recorded temperature in accessible organs reflect the intramedullary temperature in the spinal cord?

This article addresses one basic issue regarding the use of systemic hypothermia in the acute management of spinal cord injury, namely, how to interpret temperature recordings in accessible organs such as the rectum or esophagus with reference to the spinal cord temperature. Thirty-six rats, divided into six groups, were randomized to laminectomy or to severe spinal cord compression trauma, and were further randomized to either a cooling/rewarming procedure or continuous normothermia (esophageal temperature 38 degrees C) for 90 min. The first procedure comprised normothermia during the surgical procedure, followed by lowering of the esophageal temperature from 38 degrees C to 30 degrees C (the hypothermic level), a 20-min steady-state period at 30 degrees C, rewarming to 38 degrees C, and finally a 20-min steady-state period at 38 degrees C. The esophageal, rectal, and epidural temperatures were recorded in all animals. The intramedullary temperature was also recorded invasively in four of the six groups. We conclude that the esophageal temperature is safe and easy to record and, in our setting, reflects the epidural temperature. The differences registrated may reflect a true deviation of the intramedullary temperature due to initial environmental exposure and secondary injury processes. Our results indicate that the esophageal temperature exceeds the intramedullary temperature during the initial recording and final steady state following rewarming, but not during the most crucial part of the experiment, the hypothermic period. The core temperature measured in the esophagus can therefore be used to evaluate the intramedullary temperature during alterations of the systemic temperature and during hypothermic periods.

Animals↗
PubMed1998

Antibodies against double-stranded DNA and development of polymyositis during treatment with interferon.

Alpha interferons have become effective palliative treatments for patients with neuroendocrine tumours such as carcinoids and endocrine pancreatic tumours. However, several reports indicate an increased incidence of both autoantibodies and autoimmune diseases in patients treated with interferon-alpha (IFN-alpha). We studied the development of antibodies against double-stranded DNA (dsDNA) and clinical signs of autoimmune disease in 214 patients with malignant carcinoids or endocrine pancreatic tumours consecutively admitted for treatment with IFN-alpha. Seventeen patients (8%) developed antibodies against dsDNA, predominantly females (12 females and 5 males). One patient had clinical and laboratory signs of polymyositis. Among the other 16 patients, three developed hypothyroidism and in six patients the anti-dsDNA autoantibodies normalized despite continuing therapy. Although a significant number of patients developed autoantibodies against dsDNA, overt autoimmune disease related to these antibodies is a rare event and many patients spontaneously normalize these titres despite continuing IFN-alpha treatment.

Aged↗
PubMed1998

Expression of vascular endothelial growth factor (VEGF) and its receptors (Flt-1 and Flk-1) following permanent and transient occlusion of the middle cerebral artery in the rat.

Vascular endothelial growth factor (VEGF) is a known endothelial mitogen and a potent enhancer of vascular permeability although its role in focal cerebral ischemia is still not completely understood. The present report describes the immunohistochemical distribution of VEGF and its 2 receptors, Flt-1 and Flk-1 at day 1 and 3 following permanent and transient middle cerebral artery occlusion (MCAO) in the rat. A bilateral increase in VEGF immunoreactivity, particularly in neurons and blood vessels, was seen in both the experimental designs by day 1. By day 3, the immunoreactivity was restricted chiefly to the lesion side, where reaction was most prominent in the border zones of the infarcts. Immunoreaction to VEGF was more pronounced in cases of permanent MCAO than in transient MCAO. Flt-1 reaction was increased in neurons, glial and endothelial cells after both transient and permanent MCAO. Immunoreactivity to Flk-1 was prominent in glial cells and was present to some extent in endothelial cells. These findings indicate an early upregulation of VEGF and its receptors after permanent as well as transient focal cerebral ischemia in the rat.

Animals↗
PubMed1998

Accumulation of immunoreactivity to ubiquitin carboxyl-terminal hydrolase PGP 9.5 in axons of human cases with spinal cord lesions.

The protein gene product PGP 9.5 is one of the major polypeptides in neurons. It can act as a ubiquitin carboxyl-terminal hydrolase in ubiquitin-mediated degradation of proteins. The present study was performed to find out if human cases with spinal cord trauma present immunohistochemical signs of PGP 9.5 accumulation in injured axons known to accumulate ubiquitin. For comparison, we used six autopsy cases without spinal cord pathology, one case with syringomyelia, one case with ischaemic injury of the cord, and six ALS cases. Controls presented PGP 9.5-immunostained axons of weak to moderate intensity in the longitudinal tracts. Immunoreactivity was not detected in nerve cell bodies, glial cells or axons of the grey matter. All nine trauma cases showed axonal swellings, but their numbers varied. Intensely immunostained axonal swellings were particularly abundant in cases with a survival period up to 1 month after trauma. Strongly immunoreactive axons were present also in the cases with infarct and syringomyelia. In conclusion, human cases with spinal cord trauma and other focal injuries present signs of PGP 9.5 accumulation in severed axons possibly resulting from disturbed axonal transport. PGP 9.5 thus seems to be present and may take part in ubiquitin-mediated degradation of proteins in injured axons of the spinal cord.

Adult↗
PubMed1997

Effect of 21-aminosteroid on extracellular energy-related metabolites and amino acids after compression injury of rat spinal cord.

We evaluated in a rat model of severe spinal cord compression the effect of the 21-aminosteroid tirilazad on extracellular levels of energy metabolites and amino acids, until 3 h after injury. The compound was given i.v. 30 min before injury (3 mg/kg) and hourly thereafter (1.5 mg/kg). The findings were compared with previously reported effects of methylprednisolone. Both treated and untreated rats with spinal cord compression showed, at 10 min after injury, a five- to sixfold elevation of extracellular lactate above the preinjury level. There was no significant difference for lactate, pyruvate or lactate/pyruvate ratio between the treated and untreated injured groups at any time point after trauma. Glutamate was significantly elevated both in treated and untreated injured rats for 20 min after trauma. The mean glutamate level was lower in animals treated with 21-aminosteroid. However, there was no statistically significant difference between the treated and untreated rats at any time after trauma. There was no statistically significant difference between the groups for aspartate, serine, glutamine, histidine, glycine, threonine, taurine, alanine and tyrosine. In conclusion our findings indicate that, in the injured spinal cord, methylprednisolone and the 21-aminosteroid have differences and similarities, regarding their effects on energy and amino acid metabolism. The lowering of the lactate and arginine levels early after trauma seen with methylprednisolone pretreatment was absent after 21-aminosteroid pretreatment. However, the mean extracellular level of glutamate was lower with both methylprednisolone and 21-aminosteroid after injury, although the difference was not statistically significant between treated and untreated rats.

Amino Acids↗