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Biomedical subjects

Y Olsson

Publications and source records attributed to Y Olsson.

At least 109 records · Page 6Linked to original sources
PubMed1992

Characterization of prolactin receptors in human choroid plexus.

The specific binding of 125I-human prolactin (hPRL) was studied in different areas of the human brain. Particularly high binding affinity of the hormone was found in the choroid plexus and this tissue was therefore selected for further studies. The hippocampus, the hypothalamus and the pituitary were among other regions containing prolactin-binding sites. In the choroid plexus the amount of PRL receptors was significantly higher in females than in males and was also found in both sexes to decrease with age. The binding affinity of 125I-hPRL to choroid plexus was 3.0 x 10(9) M-1 and the binding capacity was 10.3 pmol per mg protein. Following solubilization with Triton X-100 the PRL receptor fraction retained its hormone-binding properties and upon molecular sieve chromatography it behaved as a protein with a molecular mass of approximately 250,000. Cross-linking of 125I-hPRL to receptors from choroid plexus and subsequent sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis indicated a major hormone-binding unit of M(r) 44,000. This value is about 7,000 smaller than that reported earlier by us for the growth hormone receptors from the same tissue, following cross-linking to 125I-human growth hormone (hGH). By affinity column chromatography a complete separation of the hPRL and hGH binding units was achieved. It was thus shown that in choroid plexus the binding sites for GH and PRL occur as discrete entities.

Aging↗
PubMed1991

Evaluation of traumatic spinal cord edema using evoked potentials recorded from the spinal epidural space. An experimental study in the rat.

Spinal cord evoked potentials (SCEP) elicited by simultaneous distal tibial and sural nerve stimulation were continuously recorded from the epidural space at the T9 and T12 levels of urethane anaesthetized rats before and after a unilateral incision (about 3 mm deep and 5 mm long) in the right dorsal horn of the T10-11 segments. The changes in SCEP were correlated with the increase in spinal cord water content measured 5 h after injury. In addition, the influence of serotonin (5-HT) in mediating such changes was explored using a pharmacological approach. The changes in SCEP immediately after injury correlated well with development of spinal cord edema measured 5 h after injury. Thus, the maximal negative peak (MNP) amplitude of SCEP decreased by an average of 64.0% immediately after injury and the water content of the spinal cord was increased from 71.6% (controls) to 77.6% 5 h after injury. Pretreatment with p-CPA (a serotonin synthesis inhibitor) prevented the initial decrease of the MNP amplitude and also the increase of water content (72.5%). On the other hand, pretreatment with cyproheptadine (a 5-HT2 receptor antagonist) enhanced both the initial decrease of the MNP amplitude as well as the increase of water content (81.3%). The results show a good correlation between changes of SCEP immediately after injury and the magnitude of spinal cord edema (r = 0.9) measured 5 h after injury. The findings reveal a major role of serotonin in mediating early changes of SCEP and later development of spinal cord edema and demonstrate a prognostic value of early SCEP recordings in predicting the final outcome of traumatic spinal cord injuries.

Animals↗
PubMed1990

Changes in blood-brain barrier and cerebral blood flow following elevation of circulating serotonin level in anesthetized rats.

Plasma serotonin (5-HT) was elevated by an intravenous infusion of this amine into urethane-anaesthetized rats and the concentration approximated that present in various neurological diseases and mental abnormalities. An infusion of 10 micrograms per kg body weight for 10 min significantly increased blood-brain barrier (BBB) permeability to Evans blue and 131I-sodium measured in whole brain. Regional BBB determinations with labelled 131I-sodium showed that the permeability to this compound was increased in the cerebral cortex, hippocampus, caudate nucleus, hypothalamus, colliculus and the cerebellum but not in the pons and the medulla oblongata. Regional blood flow was reduced in the same parts which showed BBB abnormality tested with 125I-labeled microspheres. Pretreatment with cyproheptadine, a 5-HT2 receptor antagonist, prevented the BBB increase and the regional blood flow was near normal values. Similar effects were obtained with indomethacin, a prostaglandin synthesis inhibitor. Vinblastine, known to influence vesicular transport, eliminated extravasation of the tracers but the regional blood flow remained depressed. A hypothesis is put forward that serotonin after binding to its receptor in the cerebral vessels stimulates prostaglandin which either directly or by means of cyclic adenosine monophosphate causes an increased vesicular transport across the endothelial cells and thus an extravasation of tracer substances in the brain. Obviously, this form of exudation can be influenced by pharmacological means.

Animals↗
PubMed1990

Increased 5-hydroxytryptamine immunoreactivity in traumatized spinal cord. An experimental study in the rat.

The possibility that serotonin (5-hydroxytryptamine, 5-HT) is involved in the early tissue reactions occurring in spinal cord trauma was examined in a rat model using an immunocytochemical technique. The injury was made in the form of a 5-mm long and 2.5-mm wide lesion of the right dorsal horn at the level of T10-11. Injured rats, pretreated with the 5-HT synthesis blocking agent, p-chlorophenyl alanine (p-CPA) were compared with untreated injured controls and the animals were allowed to survive for 5 h. The distribution of 5-HT was examined in proximal and distal cross- sections of the cord, located 2 and 5 mm away from the injury. Normal rats showed immunoreactive material in nerve cell processes and in a few nerve cell bodies of the ventral horns. The trauma to the spinal cord caused a marked increase in 5-HT immunoreactivity in the segments located 2 mm proximal and distal to the injury, particularly in the ipsilateral ventral horn. The segment located 5 mm distal to the lesion showed a similar increase in immunoreactivity but it was apparently less pronounced in the corresponding proximal segment. Treatment with p-CPA markedly reduced the trauma-induced increase in 5-HT immunoreactivity in all the segments. These immunohistochemical findings were in line with the changes in the contents of 5-HT measured biochemically in corresponding spinal cord segments. At the onset of the trauma to the spinal cord 5-HT is thus present in the tissue, mainly in the form of 5-HT-containing nerve cell processes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effects of p-chlorophenylalanine on microvascular permeability changes in spinal cord trauma. An experimental study in the rat using 131I-sodium and lanthanum tracers.

The possibility that serotonin can take part in the initiation of the increased microvascular permeability occurring in a spinal cord trauma was investigated in a rat model with 131I-sodium and lanthanum as tracers. We influenced the serotonin content in the tissue pharmacologically by treating animals with a serotonin synthesis inhibitor, p-chlorophenylalanine (p-CPA), before the production of the injury and compared the results with injured, untreated controls. A small incision was made in the dorsal horn of the lower thoracic cord. It caused a progressive extravasation of 131I-sodium in the damaged segment, measured after 1, 2 and 5 h. Rostral and caudal segments also showed a significant but lower accumulation of 131I-sodium. Lanthanum added to the fixative was used as an ionic tracer detectable by electron microscopy. The endothelial cells of microvessels removed from the perifocal region after 5 h showed a marked increase in the number of lanthanum-filled vesicles. Many endothelial cells had a diffuse penetration of the tracer into the cytoplasm and the basement membrane. However, the tight junctions usually remained closed to lanthanum. Pretreatment with p-CPA markedly reduced the extravasation of 131I-sodium measured at 5 h in the traumatized cord. At the cellular level, the endothelial vesicles filled with lanthanum approached the condition of uninjured animals. The diffuse infiltration of lanthanum into endothelial cells and its spread into the basement membrane of the vascular wall were usually absent. Our results indicate that serotonin plays a role in the initiation of the increased microvascular permeability which occurs in spinal cord injuries.

Animals↗
PubMed1990

Edema formation and cellular alterations following spinal cord injury in the rat and their modification with p-chlorophenylalanine.

The possibility that serotonin can modify the early pathological sequences occurring in spinal cord trauma was investigated in a rat model. To that end we took advantage of the possibility of influencing serotonin pharmacologically by treating animals with a serotonin synthesis inhibitor, p-chlorophenylalanine (p-CPA) before the production of the injury and compared the results with injured, untreated controls. A unilateral incision was made into the dorsal horn of the lower thoracic cord (about 2.5 mm deep, 4.5 mm long) and the rats were allowed to survive up to 5 h after the trauma. The injured region from untreated animals showed macroscopically at that time a pronounced swelling and the water content had increased by 3.5% as compared to intact controls. The segments rostral and caudal to the lesion also exhibited a profound increase in water content. Light microscopy revealed a significant expansion of the spinal cord as compared to controls. The swelling was most pronounced in the gray matter on the injured side. Electron microscopy showed distorted neurons, swollen astrocytes and extracellular edema in the gray matter in and around the primary lesion. There was also a sponginess in the surrounding white matter with disruption of myelin, collapsed axons and widened periaxonal spaces. Pretreatment of the rats with p-CPA significantly reduced the swelling of the injured spinal cord and there was no visible expansion. The ipsilateral edema in the central gray matter was considerable less pronounced as compared to that in untreated animals. The increase in water content was less than 1% in these animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Vascular permeability of spinal nerve roots. A study in the rat with Evans blue and lanthanum as tracers.

The permeability of blood vessels in rat spinal nerve roots was investigated with Evans blue-albumin as an in vivo macromolecular tracer and lanthanum nitrate as an electron microscopic ionic marker added to a fixative. Rats injected intravenously with Evans blue, showed macroscopic distinct staining of dorsal root ganglia, whereas spinal nerve roots remained unstained. Fluorescence microscopy, however, revealed clear extravascular fluorescence both in ventral and dorsal roots 2 or 18 h after tracer administration. Two different types of blood vessels exists in spinal nerve roots; large extrinsic (radicular) in the root sheath and minute intrinsic vessels in the parenchyma. Lanthanum added to a fixative, perfused through the vessels was detected in the lumen of both types of vessels, usually adhering to the luminal plasma membrane and in many invaginations from that membrane. Lanthanum also entered the clefts between endothelial cells but was always stopped at the junctions which are, thus, of the tight type. Diffuse penetration of the compound into the cytoplasm was seen in one endothelial cell, but no fenestrations were detected. Junctions between the endothelial cells of vessels in rat spinal nerve roots are impermeable to lanthanum and most likely also to other large molecular substances like albumin. Thus, probable routes for serum albumin to enter the nerve roots, where it normally is present, must be either by centripetal extracellular diffusion from the ganglia and the peripheral nerve or by vascular leakage in the roots, caused by for instance pinocytosis across endothelial cells.

Animals↗
PubMed1990

Early accumulation of serotonin in rat spinal cord subjected to traumatic injury. Relation to edema and blood flow changes.

Changes in the concentration of serotonin (5-hydroxytryptamine) in the early period after a focal traumatic injury to rat spinal cord were determined and related to the formation of edema and alterations in blood flow. A unilateral, 5-mm-long and 3-mm-deep traumatic injury located 2 mm from the midline was created in the T10-11 segment of the cord. Five hours after the injury the serotonin concentration in the traumatized segment had increased more than 100% compared with controls. There was also a progressive increase in water content of the traumatized segment measured 1-5 h after the injury. On the other hand, the spinal cord blood flow showed a progressive decrease to about 35% of its initial value at 5 h. Pretreatment with p-chlorophenylalanine, a serotonin synthesis inhibitor, impeded the elevation in water content measured 5 h after the trauma. The spinal cord blood flow remained close to normal values and the increase in serotonin was absent. Our results show that trauma to the rat spinal cord will induce changes in the serotonin concentration of the tissue and that the associated formation of edema and blood flow alterations can be alleviated in serotonin depleted rats. Obviously, serotonin plays a significant role in the pathophysiology of traumatic injury of rat spinal cord.

Animals↗
PubMed1990

Alteration of substance P after trauma to the spinal cord: an experimental study in the rat.

The distribution of substance P was determined in the rat spinal cord and brain after a focal traumatic injury to the thoracic region (T10-11) of the spinal cord. There was at 1 and 2 h after the injury a statistically significant increase of the substance P content not only in the injured segment but also in samples removed 5 mm proximal (T9) and distal (T12) to the lesion. At 5 h the substance P content of the injured segment of the cord was reduced by 30% compared with controls. However, there was a significant increase in the concentration of this peptide in segments located 5 mm cranial and caudal to the injury (65% and 22%, respectively). Interestingly, the whole brain content of substance P showed a statistically significant 22% increase from control values at 5 h after the injury. At 1 and 2 h after the spinal cord injury there was a significant decrease in whole brain substance P concentration by 25% and 65%, respectively. Pretreatment with p-chlorophenylalanine (a serotonin synthesis inhibitor) markedly reduced the endogenous content of substance P in whole brain of normal animals. In these animals, the spinal cord content of the peptide was elevated by 83-123% as compared to untreated control animals. Spinal cord trauma inflicted on p-chlorophenylalanine-treated animals did not affect the brain peptide level at all. However, a profound decrease was noted in all the spinal cord segments at 5 h as compared to the untreated traumatized group. The decrease in this peptide was more pronounced in the cranial and the injured segments as compared to the caudal one.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Neuropathological changes and neurological function after spinal cord compression in the rat.

As part of a series of experimental investigations of the effects of various pharmacological agents on the outcome of compressive spinal cord trauma in the rat, the time course of the cell changes in the cord at the site of and distal to the compression was studied at the light microscopic level. The degree of compression used with the present model results in a transient paraparesis that recovers almost completely over a period of 3 weeks as judged by the inclined plane technique. The most significant morphological findings were as follows. Initially (1 and 24 h after the impact) there was pronounced swelling and hemorrhage at the compression site, chiefly in the gray matter of the cord. On day 4 there was severe necrosis in the same region, with numerous macrophages and leukocytes. Rats killed after 21 days showed either minor residual signs of necrosis or essentially normal tissue architecture. Surprisingly, necrosis with delayed onset also developed in the dorsal columns, involving the pyramidal tracts. This necrosis was detected in animals killed after 9 and 21 days but not in those observed after 4 days or earlier. The longitudinal tracts of the white matter showed reduced staining in paraffin sections of the compression site. Epon sections revealed splits in the myelin sheaths and enlarged periaxonal spaces as early as 1 h after the impact. The alterations in the longitudinal tracts persisted throughout the 21-day observation period and extended down to L2-L4. There was gradual functional recovery, documented by the inclined plane test. Preinjury values were almost reached on day 21, although the cord still showed some morphological damage. In individual animals, no relation was found between degree of function as tested by inclined plane and extent of morphologic injury. Additional functional and morphological methods obviously are needed in future investigations of the effects of treatments on the outcome of compressive spinal cord injury.

Animals↗
PubMed1990

Presence of plasma proteins in spinal nerve roots. An immunohistochemical study in the rat.

The presence of plasma proteins in the spinal nerve roots of normal rats was investigated using an avidin-biotin peroxidase technique on formaldehyde-fixed, paraffin-embedded material. Sections from the roots, exposed to a rabbit-anti rat albumin antiserum showed widespread, intense immunoreactivity which filled the spaces between the nerve fibers. The reaction product usually ended at the junction between the roots and the spinal cord. The sheath enclosing the roots showed the same strong immunoreaction. There was also a marked reaction in the dorsal root ganglia and peripheral nerve. Spinal cord sections, however, showed no extracellular reactivity, but many motor neurons of the ventral horn were distinctly positive, presumably the result of a normally occurring retrograde axonal transport from the periphery. Parallel sections from the roots exposed to rabbit anti rat IgG antiserum, rabbit anti rat IgM antiserum, rabbit anti human fibrinogen antiserum and rabbit anti human fibronectin antiserum revealed no positive immunoreaction. Thus, rat spinal nerve roots normally contain material with albumin antigenic properties. This would indicate that albumin is present in the extracellular fluid of the roots in the same way as in the endoneurium of peripheral nerves. The fluid microenvironment of the roots, therefore, appears to be different from that in the CNS which lacks extracellular albumin due to the impermeability of the blood-brain barrier.

Animals↗
PubMed1990

Microenvironment of the peripheral nervous system under normal and pathological conditions.

The peripheral nervous system (PNS) is composed of neurons and their processes which are located in a special fluid microenvironment. As is well known, complex biological functions such as those going on in peripheral nerves are best carried out when there is homeostasis, i.e., in a constant internal milieu. This paper is concerned with the maintenance of the homeostasis in the PNS under normal and pathological conditions. Diffusion barriers located in the intrinsic vessels of the PNS and the perineurium have the capacity to regulate the environment around the nerve fibers and to keep it away from the blood and the extracellular fluid outside the PNS. Endoneurial vascular permeability has similarities to that in the central nervous system, but compared with the blood-brain barrier the blood-nerve barrier is less efficient. This implies that toxic and infectious agents as well as some drugs have easier access to the parenchyma in nerves than to the brain parenchyma. However, ganglionic vessels lack an efficient vascular barrier to many substances which is important in intoxications caused by, e.g., doxorubicin, lead, mercury, and cadmium. It has also a significance in herpes zoster infection and presumably in Guillain-Barré syndrome. The diffusion barriers may themselves be influenced by pathologic processes and can then respond with an increased permeability. This may lead to the formation of edema in the PNS, i.e., one of the cardinal features of many diseases in nerves of traumatic, toxic, and inflammatory nature. Such a response had negative as well as positive implications. Severe edema may disturb the normal microcirculation in the endoneurial vessels and stimulate collagen production and fibrosis. However, the presence of a protein-rich endoneurial edema may well be important in repair processes such as reduplication of Schwann cells and growth of axons.

Animals↗
PubMed1989

Effects of the noradrenaline neurotoxin N-2-chloroethyl-N-ethyl-2-bromo-benzylamine hydrochloride (DSP4) on the blood-brain barrier. An experimental study in the mouse using protein tracer and density determination techniques.

Cerebral microvessels receive a noradrenergic innervation originating from the locus coeruleus. Previously, many studies have tried to elucidate the role of the central noradrenergic innervation on the blood-brain barrier (BBB). Many of them are based on chemical destruction of the innervation by local injection of 6-hydroxydopamine (6-OHDA) or physical injury to the locus coeruleus. Such methods are not selective and the results reported are contradictory. We have treated mice with a single i.p. injection of the compound, N-2-chloroethyl-N-ethyl-2-bromo-benzylamine hydrochloride (DSP4). This substance induces a selective noradrenaline depletion and, unlike 6-OHDA, it can pass into the brain after an i.p. injection. The animals were allowed to survive for 6 h to 60 days and the BBB was investigated with i.v.-injected horseradish peroxidase (HRP). Brain density values were also determined to find out of edema developed. The light microscopic distribution of HRP in the brain of DSP4-treated animals did not differ from that in control mice, i.e., there were no signs of increased BBB permeability to this protein tracer caused by DSP4. Density determinations revealed statistically significant reduced values in cerebrum (P less than 0.005) and rhombencephalon (cerebellum) (P less than 0.0005) of animals given 100 mg/kg body wt. of DSP4 indicating development of edema. A minor drop in density of the rhombencephalon (cerebellum) (P less than 0.05 at 48 h) and of the cerebrum (statistically not significant) appeared when 50 mg/kg body wt. of DSP4 was injected.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Blood supply of spinal nerve roots. An experimental study in the rat.

The blood supply of rat spinal nerve roots was investigated using a variety of methods, including preparation of vascular casts with Microfil, alkaline phosphatase histochemistry and Epon embedding for light and electron microscopy. Dorsal and ventral roots were sampled and portions from the spinal cord, dorsal root ganglia and peripheral nerve were taken for comparison. There were two different types of vessels in the roots; the large extrinsic (radicular) and the minute intrinsic vessels of the nerve root parenchyma. The radicular vessels follow a straight course along the longitudinal axis of both ventral and dorsal roots. Their diameter appears to vary in different topographical regions. They are united with the longitudinal spinal cord arteries and are a major source of arterial supply to the spinal cord. There are also many small communicants with the intrinsic root vasculature. The radicular vessels are located in the root sheath and are surrounded by cells and collagen fibers forming this sheath. The intrinsic vessels of the spinal roots form a plexus of minute vessels, chiefly capillaries. Most of them are longitudinally arranged along the roots but there are also many loops and twisted portions. There are many direct connections to neighbouring vascular networks. The microvessels are surrounded by a basement lamina and wide, collagen containing extracellular spaces. The intrinsic vascularization of the roots is similar to that in the endoneurium of peripheral nerves, i.e., chiefly a plexus of minute vessels. Many direct communicants exist between these intrinsic vessels and blood vessels in the spinal cord parenchyma, ganglia and nerve.

Alkaline Phosphatase↗
PubMed1989

Role of histamine in traumatic brain edema. An experimental study in the rat.

The possibility that histamine plays a role in the formation of traumatic brain edema was investigated in the rat. A 3 mm deep and 3 mm long stab injury was performed in the right parietal cortex under urethane anaesthesia. The brain water content and histamine levels in plasma and brain were measured at the end of 1, 2 and 5 h periods after trauma. There was a 3.46% increase in brain water content in the traumatized hemisphere from the value in the control group at 5 h. The histamine content was increased by 107% in plasma and 51% in the traumatized brain hemisphere from the control value at this time period. The increased brain water content as well as the elevated plasma and brain histamine levels were prevented by prior treatment with the histamine H2-receptor antagonist cimetidine. Mepyramine (a histamine H1-receptor antagonist) failed to reduce the increased brain water content and the histamine levels in plasma and brain remained high. The results strongly indicate that histamine has a role in the formation of early traumatic brain edema and that this reaction can be influenced by pharmacological procedures.

Animals↗
PubMed1989

Distribution and toxic effects of intravenously injected epirubicin on the central nervous system of the mouse.

Epirubicin (4'-epi-doxorubicin) is a new anthracycline cytostatic, which was synthesized in an effort to find an agent with an improved therapeutic effect on human malignant tumours combined with reduced myocardial toxicity. Animal experiments have previously shown that the parent drug doxorubicin, besides being a myocardial toxin, may cause nerve cell lesions both in the central and the peripheral nervous system. Intravenously (i.v.) injected doxorubicin passes into regions of the nervous system located outside the blood-brain barrier (BBB); the drug accumulates in the nucleus of neurons and causes cell degeneration. This investigation was performed to establish whether epirubicin, given as a single i.v. injection in the mouse, could enter the central nervous system (CNS) and cause neurotoxic effects. Epirubicin was found to emit a primary orange fluorescence in thin frozen sections. Detectable amounts of epirubicin could not be seen in regions protected by the BBB. The choroid plexus and all the circumventricular brain regions with the exception of the subcommissural organ showed the presence of the drug in the parenchyma and a marked accumulation in cell nuclei. Severe cellular changes were found in these regions by light and electron microscopy and the alterations were most marked in mice with the longest survival period (45 days). The animals also developed a progressive sensory polyneuropathy and appeared lethargic. Epirubicin given as a single i.v. injection in the mouse will thus spread into brain regions lacking a BBB where it produces toxic lesions in the same way as previously reported for the parent compound, doxorubicin.

Animals↗
PubMed1989

Neurologic and neuropathologic outcome after middle cerebral artery occlusion in rats.

Focal cerebral ischemia was produced in 45 rats by occlusion of the left middle cerebral artery. Groups of rats were investigated over a long period after occlusion, that is, from a few hours to 42 days after the production of focal ischemia. Light microscopy showed infarcts in the frontoparietal cortex and the lateral caudoputamen. The ischemic changes closely resembled those found in ischemic infarcts in humans and followed a similar pattern over time. Measurements of the sizes of the infarct, the ipsilateral (operated) hemisphere, and the contralateral hemisphere from camera lucida drawings revealed that the infarct size changed with time after occlusion. Rats killed during the first 7 days (acute phase) had the largest infarcts; in rats killed thereafter, the infarct size diminished. The size of the ipsilateral hemisphere also changed with time; during the first 7 days after occlusion this hemisphere was swollen and larger than the contralateral hemisphere. We suggest that these acute changes are caused by cerebral edema. After the first 7 days, enlargement of the ipsilateral hemisphere gave way to a significant reduction in the size of both the ipsilateral hemisphere and the infarct. We believe that the major reasons for this shift in size are resorption of fluid together with diminished production of edema and elimination of dead cells by macrophages. We suggest that the amount of tissue loss (i.e., the degree of atrophy and the remaining infarct "scar") found 21-42 days after occlusion (during the late phase) is a measure of the total amount of tissue that succumbed as a consequence of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗