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Biomedical subjects

O Kempski

Publications and source records attributed to O Kempski.

At least 109 records · Page 6Linked to original sources
PubMed1990

Brain oedema and intracranial pressure in superior sagittal sinus balloon occlusion. An experimental study in pigs.

About 2/3 of all patients with thrombosis of the superior sagittal sinus (SSS) develop signs of increased ICP and/or brain oedema (BE). The time of onset and the spectrum of symptoms in SSS thrombosis vary extremely. This variability might be caused by differences in pathomechanism like BE and rise of ICP, parameters studied in the present contribution. 10 domestic pigs received a standardized occlusion of the SSS with two different balloon types (spherical and cylindrical). They were monitored for several systemic and intracranial pressures. After 4 hours of occlusion the brains were examined for BE (Evans blue, water content). They were compared with those of 4 sham-operated control animals. 4 animals underwent cerebral angiography. Within 4 hours ICP rose to 60 mm Hg in the group with the spherical balloon. Normal ICP of 5-10 mm Hg was seen in the group with the cylindrical balloon and in the sham-operated controls. The water content of the white matter was elevated in both occlusion groups differing significantly from the control group. Haemorrhagic infarction of the frontal parts of the cerebrum occurred in animals with concomitant obliteration of bridging and cortical veins. We conclude from our experiments that SSS occlusion may initiate a multitude of possible pathomechanisms depending on the involvement of bridging veins, cortical veins and inner brain veins.

Animals↗
PubMed1990

Prominent white matter lesions develop in Mongolian gerbils treated with 100% normobaric oxygen after global brain ischemia.

Carotid arteries were occluded bilaterally for 15 min in two groups of Mongolian gerbils. The first group received 100% oxygen during the first 3 h of reperfusion. During that period, room air was given to the second group. After 3 h, both groups received room air. Brains of gerbils that died within 14 days after occlusion were removed, fixed in formalin and embedded in paraffin. Gerbils that survived 15-28 days were perfused with formalin before their brains were removed and embedded in paraffin. Adjacent, serially cut sections were stained with luxol fast blue (LFB)-H&E, cresyl violet, according to the Bodian method, or immunocytochemically with antisera raised against myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP). In brain sections of gerbils receiving 3 h of 100% oxygen, there were circumscribed white matter lesions in the corpus striatum, lateral thalamus, mesencephalon and posterior limb of the internal capsule. Myelin sheaths were swollen, fragmented and were less intensely stained by MBP antiserum. MBP and LFB-stained myelin fragments were present extracellularly and in macrophages. Many axons in these areas appeared undamaged. Previously described ischemic changes were found in gray matter and some areas of white matter in both groups. However, neurons in the deeper laminae of the cerebral cortex appeared to be better preserved in gerbils given oxygen. The results suggest that hyperoxia, if present immediately after transient brain ischemia, may damage myelin more severely than other cellular elements.

Animals↗
PubMed1990

Effects of lactacidosis on glial cell volume and viability.

Effects of severe lactacidosis were analyzed in vitro by employment of C6 glioma cells and astrocytes from primary culture. The cells were suspended in a physiological medium, which was rendered acidotic by addition of lactic acid in rising concentrations. A pH range of 7.4-4.2 was studied under maintenance of isotonicity and a normal electrolyte concentration of the medium. Cell swelling was quantified by flow cytometry using an advanced Coulter system with hydrodynamic focusing. The method was also utilized for assessment of cell viability by exclusion of the fluorescent dye propidium iodide. The volume of C6 glioma cells was found to increase if the pH was titrated to pH 6.8 or below. From this level downward, the extent of cell swelling depended on the degree of acidosis and the duration of exposure. For example, lactacidosis of pH 6.2 for 60 min led to an increase in cell size to 124.5% of normal, while pH 5.0 or 4.2 led to a cell size of 151.1 or 190.9%, respectively. A comparative analysis of the acidosis-induced cell swelling was made by using sulfuric acid. Swelling of C6 glioma at a given pH was only half of what was found when using lactic acid. This indicates specific swelling-inducing properties of lactic acid, while cell viability was not differently affected by both acids. Of the C6 glioma cells, 89.1% were viable under control conditions at pH 7.4. The viability remained unchanged down to pH 6.2. At pH 5.6, viability remained normal for 30 min, but it decreased to 73.4% after 60 min. Further lowering of pH to 5.0 or 4.6 respectively, decreased the number of viable cells to 47.8 or 40.3%. At pH 4.2 only 21.1% of the cells were surviving 1 h of lactacidosis. Cell swelling from lactacidosis could be largely inhibited by replacement of Na+ and bicarbonate ions in the medium by choline chloride and N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid buffer, suggesting an involvement of the Na+/H+ and Cl-/HCO3- antiporters in the swelling process. Omission of Na+ and bicarbonate was, however, associated with reduced viability of the glial cells in acidosis. The swelling response of astrocytes obtained from primary culture was similar to that of C6 glioma. Lactic acid was also more effective in inducing cell swelling than sulfuric acid at the same level of acidosis. In astrocytes, viability at, e.g., pH 5.6 appeared to be more affected by lactic than by sulfuric acid.(ABSTRACT TRUNCATED AT 400 WORDS)

Acidosis, Lactic↗
PubMed1990

Intravenous glutamate enhances edema formation after a freezing lesion.

The effect of intravenous infusion of glutamate on edema formation after a freezing lesion in rats is reported. Twenty-four hours of continuous intravenous glutamate application led to a significant increase of hemispheric swelling, and of the water and sodium content as compared with animals receiving infusions of physiological saline after trauma. The results suggest that glutamate entering the e.c. space together with the edema fluid causes additional cytotoxic edema as a consequence of an enhanced glutamate uptake by the glia. Therefore, the use of amino acid infusions containing glutamate for parenteral nutrition may present an additional risk for neurosurgical patients with a disturbed BBB.

Animals↗
PubMed1990

Molecular mechanisms of glial cell swelling in acidosis.

The mechanism of glial swelling in acidosis were investigated in an in vitro model. C6 glial cells were exposed to pH levels between 7.4 and 6.2. The cell volume response was determined by flow cytometry. Cell swelling of 110% to 115% was observed if pH was reduced to 6.8 or below. This effect was independent of the length of exposure to acidosis. Swelling induced by pH could be attenuated by (a) inhibition of the Na+/H+ antiporter by amiloride, (b) replacement of bicarbonate by HEPES, and (c) inhibition of carbonic anhydrase by acetazolamide. Absence of Na+ ions from the incubation medium completely prevented acidosis-induced glial swelling. Inhibition of the Cl-/HCO3- antiporter reduced swelling only in its first phase. The results suggest that glial swelling in acidosis may be from an activation of anion and cation antiporters as an attempt to maintain a normal intracellular pH. It is concluded that swelling of glial cells in the ischemic penumbra zone evolves along similar mechanisms.

Acetazolamide↗
PubMed1990

An improved closed cranial window technique for investigation of blood-brain barrier function and cerebral vasomotor control in the rat.

A modification of the closed cranial window technique for small laboratory animals is presented. The method facilitates investigation of blood-brain barrier permeability in association with studies of the cerebrovascular response under normal and pathological conditions. Following trephination and preparation of the pia-arachnoid surface, the skull defect is closed again by sealing a cover glass onto a wall of dental cement surrounding the cranial window. The intracranial pressure can then be studied and experimentally manipulated. Care is taken to maintain normal blood-brain barrier function to a small barrier indicator (Na(+)-fluorescein, MW: 376). This is accomplished by opening the skull and dura mater under a column of paraffin oil to avoid exposure of brain tissue to atmospheric pressure. Reactivity of the cerebral surface vessels was assessed during hypercapnia at an arterial PaCO2 of 50.8 +/- 1.1 mm Hg. It was found that small arterioles of 20-50 microns phi had a significantly larger CO2-response than large arterioles of 50-100 microns phi. Pial venules did not respond at all. Superfusion of the cranial window preparation at a rate of 5 ml/h with buffered artificial CSF was tolerated for hours. No alterations of arteriolar or venular diameters nor opening of the blood-brain barrier to Na(+)-fluorescein was observed. These technical modifications enable us to employ a closed cranial window model in small laboratory animals for studies of cerebral microcirculation and blood-brain barrier function under normal as well as under pathological conditions related to brain damage.

Animals↗
PubMed1989

Mechanisms of ischemic cerebral damage: the role of glial cells.

Glial cells exert an important homeostatic function in the brain in protecting neurons from extracellular mediators of secondary brain damage. In vitro studies suggest that glial swelling as observed in ischemia is not simply an indication of glial damage but rather of the activation of glial homeostatic functions. The mechanisms of glial swelling due to exposure to glutamate and acidosis, as well as therapeutic consequences, are discussed.

Journal Article↗
PubMed1989

Release of glutamate and of free fatty acids in vasogenic brain edema.

The pathophysiological potential of mediator substances in manifestations of secondary brain damage is attracting increased attention. This is particularly true of the excitatory transmitters glutamate and arachidonic acid. Noxious properties of these compounds in central nervous tissue have been demonstrated. The current study was performed to determine whether glutamate and arachidonate are released in brain tissue secondary to focal trauma. For this purpose, a cold injury of exposed cerebral cortex was induced in cats. Marked accumulation of glutamate was observed in interstitially drained edema fluid, reaching 10 to 15 times the level that was assessed in normal cerebrospinal fluid (CSF) prior to trauma. The extracellular release of glutamate was further dramatically enhanced by a critical decrease of the cerebral perfusion pressure due to a malignant increase of intracranial pressure. Under these conditions, glutamate concentrations 1000 to 1500 times normal levels accumulated in vasogenic edema fluid, demonstrating a relationship between the extent of the release of glutamate in damaged brain and the severity of the insult. Although under normal conditions glutamate concentrations in plasma were considerably higher than in the interstitial fluid, the pronounced increase of glutamate in this compartment due to trauma cannot be explained by transport of the compound together with the plasma-like edema from the intravascular space. Corresponding findings were obtained for free fatty acid concentrations in edema fluid. Almost all fatty acids that were studied had a significantly higher concentration in edema fluid than in normal CSF obtained as a control prior to trauma. However, contrary to the findings for glutamate, fatty acid concentrations in edema fluid were lower than in plasma. Accumulation of fatty acids in vasogenic edema fluid might, therefore, have resulted from uptake of the material together with edema fluid through the breached blood-brain barrier. Arachidonic acid was an exception. Its concentrations were significantly higher in edema fluid than in plasma, suggesting that it was released from cerebral parenchyma as the underlying mechanism of its extracellular accumulation. The current observations provide further support for a mediator function of glutamate and arachidonic acid in acute traumatic lesions of the brain. Quantitative assessment of the release of highly active mediator substances in brain tissue may facilitate analysis of the therapeutic efficiency of specific treatment aimed at interfering with the release or pathological function of mediators of secondary brain damage.

Animals↗
PubMed1988

Determinants of survival after forebrain ischemia in Mongolian gerbils.

Mongolian gerbils were exposed to 15 min of cerebral ischemia. Quantitative histology was used to establish neuronal damage in the CA1, CA2/3, and CA3 sectors of the hippocampus 2 weeks after the insult. Seven moribund animals were sacrificed earlier to examine whether there is a correlation between hippocampal damage and mortality. Surviving animals had a 86.6% loss of CA1 neurons. In the CA2/3 and CA3 sectors 62.7 and 72.6% of the neurons were preserved. Moribund animals had a further dramatic loss of nerve cells in these sectors, to 14.8 and 20.3%, respectively. The reduction of CA2/3 neurons and survival time were correlated. In addition, gerbils which would later become moribund were found to have a significant increase in plasma osmolarity from 319 to 342 mosm/liter and of hematocrit from 47.4 to 53.9 at day 4 after ischemia.

Animals↗
PubMed1988

Mediators of brain edema and secondary brain damage.

Progress is our understanding of the roles of vasogenic and cytotoxic brain edema in secondary brain damage can be expected from studies of the ability of biochemical factors to open the blood-brain barrier, derange the microcirculation, and cause cell swelling and necrosis. Mediator compounds are considered to form or to become released in an area of primarily damaged brain (necrosis) and to enter the cerebral parenchyma through the broken blood-brain barrier from the intravascular space. Many biochemical factors must be considered. We suggested three criteria for determining the roles of mediators: a) they must inflict brain tissue damage, b) they must occur in pathologic concentrations or in compartments not normally present, and c) specific inhibition should attenuate secondary brain damage. These requirements are met by the kallikrein-kinin system and by glutamate. In the case of arachidonic acid and its many metabolites, the concept is difficult to test because fatty acids may be active only if not bound to proteins, and therapeutic inhibition might be difficult. A variety of mediators may enhance each other in a cascade manner by various initiating reactions that might be amenable for pharmacologic inhibition.

Animals↗
PubMed1988

Glial swelling during extracellular acidosis in vitro.

Intracellular and extracellular acidosis may determine the ultimate outcome for brain tissue in cerebral ischemia. An extracellular acidosis that occurs in the penumbra zone was investigated in vitro as to its role in the formation of cytotoxic cell swelling. For that purpose, C6 glioma cells or primary cultured astrocytes were suspended in normal isotonic medium in normoxia during acidification to a final pH of 6.2. The cell volume response was determined by flow cytometry using hydrodynamic focusing, which allows one to recognize changes in cell size of less than 1%. A threshold pH of 6.8 was found that had to be crossed to induce cell swelling by acidosis. Once pH fell below this threshold, the increase in cell size appeared to be an all-or-nothing phenomenon. The cells rapidly assumed a final cell size of 115% of normal in the case of C6 glioma or of 118% in the case of primary cultured astrocytes independent of the actual level of acidosis or the duration of exposure. Acidosis-induced glial swelling could be significantly attenuated by 1) addition of amiloride, 2) administration of acetazolamide, or 3) replacement of bicarbonate buffer against N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES). Replacement of extracellular Na+ by choline chloride led to complete prevention of the acidosis-induced cell swelling. Taken together, the findings strongly indicate a central involvement of Na+/H+ and Cl-/HCO3- exchange mechanisms in the development of cell swelling under these conditions. Activation of the Na+/H+ antiporter can be considered an attempt to maintain a normal intracellular pH at the expense of an abnormal cell volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1988

Cyclohexyl adenosine protects against neuronal death following ischemia in the CA1 region of gerbil hippocampus.

Sixty-five male gerbils were exposed to 30 minutes of cerebral ischemia induced by a bilateral carotid artery occlusion. One group of 15 gerbils received a single injection of 25 microliter of 5 microM cyclohexyladenosine into the cerebral ventricle 15 minutes after release of the occlusion. Another group of 45 gerbils received a similar injection of the vehicle. Five days after ischemia, the hippocampal histology was examined under light microscopy. In the gerbils treated with the adenosine receptor agonist N-6-cyclohexyladenosine, the CA1 region of the hippocampus showed significant quantitative pyramidal cell preservation (p less than 0.01, Mann-Whitney U test). Qualitatively, substantial destruction of CA1 neurons was present in all hippocampi of the vehicle-injected gerbils. The CA1 neurons in the cyclohexyladenosine-treated gerbils did not differ from those seen in the five nonischemic controls. The precise mechanism of the protective action of cyclohexyladenosine is unknown, although it has been demonstrated that adenosine agonists reduce presynaptic glutamate release in vitro. It is possible that postischemic administration of cyclohexyladenosine decreases the release of this neurotransmitter in the intact brain as well. The concomitant reduction of the neurotoxic effect of glutamate may, therefore, result in better histologic preservation of the pyramidal cells in the postischemic CA1.

Adenosine↗
PubMed1987

Cerebromicrovascular endothelial permeability. In-vitro studies.

Permeability of cerebromicrovascular endothelium has been investigated in a new model of cultured cells. The endothelial cells are grown on dextran microcarriers and constitute a barrier for trypan blue (TB) binding to the dextran beads. Changes in the permeability of microcarrier-cultured endothelium have been investigated during the exposure of cells to arachidonic acid or substances involved either in arachidonate metabolism or stimulation of cAMP. The results demonstrate enhanced TB passage through the endothelial barrier during exposure to high concentrations of arachidonic acid and indomethacin, but not to ibuprofen. The effect of indomethacin could be prevented by pretreatment with dexamethasone. Dexamethasone alone did not influence the barrier. Forskolin, a drug which stimulates the catalytic unit of adenylate cyclase, did not affect the endothelial permeability to TB. These findings support the contention that substances derived from a disturbed cellular membrane contribute to the altered blood-brain barrier function found under pathological conditions.

Animals↗
PubMed1987

Effects of forskolin on growth and morphology of cultured glial and cerebrovascular endothelial and smooth muscle cells.

The present experiments were designed to evaluate the effectiveness of forskolin on cAMP production, growth and morphology on cell cultures of glia, endothelium and smooth muscle derived from brain microvessels. Forskolin significantly increased formation of cAMP and decreased incorporation of thymidine in all three cell types. The thymidine incorporation was reduced dose-dependently with maximal growth inhibition at 100 microM forskolin. A 1 hr preincubation with forskolin abolished thymidine incorporation by cells grown in fetal calf serum (FCS)-containing media over the following 24 hr. In cerebromicrovascular endothelium and smooth muscle, forskolin caused drastic and immediate changes of cell morphology and F-actin composition that were reversible. In glial cells, morphological changes were visible only after exposure to forskolin for more than 24 hr. These changes were accompanied by increased staining with antibodies against glial fibrillary acidic protein (GFAP). These findings support the contention of cAMP involvement in growth regulation of these cells and indicate that forskolin might be used as a tool to induce growth arrest and possible differentiation in cell cultures from mammalian brain.

Animals↗
PubMed1987

Therapeutic effect of dexamethasone in T-2 toxicosis.

T-2 Toxin is a mycotoxin that induces toxemia characterized by numerous hematological and biochemical changes. We have previously shown that prostaglandin (PG) production in brain tissue is increased following T-2 toxin. The present study was designed in order to test the effect of dexamethasone on brain prostaglandins and survival of rats subjected to T-2 toxin. Furthermore, the effect of BW 755c, a dual inhibitor of the cyclooxygenase and lipoxygenase pathways of arachidonate metabolism, on the survival of rats exposed to T-2 toxin was also examined. The present study demonstrated that dexamethasone increases the survival of rats exposed to a highly lethal T-2 toxicosis. This effect was demonstrated at low as well as high doses and at different times after T-2 administration. Dexamethasone depressed PGE2 levels in the brain cortex 6 hr after T-2 toxin but abolished the reduction of PGE2 in brain cortex seen 24 hr after T-2. BW 755c had no consistent effect on the survival of rats in T-2 toxicosis. It is suggested that dexamethasone might be a useful therapeutic agent in T-2 toxicosis in animals and humans, but its mechanism of action remains obscure.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1986

Interaction between myelin basic protein-sensitized T lymphocytes and murine cerebral vascular endothelial cells.

Lymph node cells from SJL mice immunized with guinea pig myelin basic protein proliferate in vitro to the same antigen. This proliferative response is abolished by depletion of macrophages-monocytes, but can be reconstituted by the addition of cerebral vascular endothelial cells (EC) freshly isolated from syngeneic mice with adoptively transferred acute experimental allergic encephalomyelitis (EAE). Reconstitution by EC from mice with EAE can be blocked by pretreatment of EC with syngeneic anti-I-A antisera. Freshly isolated EC from normal syngeneic mice do not restore responsiveness, but can be induced to present antigen by culture with murine recombinant immune interferon-gamma or supernatants from a variety of immune cell cultures. These findings are consistent with the hypothesis that immune cells release interferon and/or other soluble factors which induce I-A molecules on EC, which subsequently acquire the capacity to present antigen. The implications of these findings relate to the migration of cells across the blood-brain-barrier into the central nervous system, and are of importance in the understanding of the pathogenesis of several neurologic disorders.

Animals↗