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Biomedical subjects

A Baethmann

Publications and source records attributed to A Baethmann.

At least 127 records · Page 7Linked to original sources
PubMed1990

The effect of various steroid treatment regimens on cold-induced brain swelling.

The role of steroid therapy in brain oedema following acute cerebral lesions is still unsolved. This study was conducted to compare the efficacy of dexamethasone and triamcinolone, and to analyze the influence of timing and duration of treatment on cold-induced brain swelling. In rabbits, a cryogenic lesion of the left parietal cortex was induced. 24, or 48 hrs after trauma, hemispheric swelling, water- and electrolyte-contents were measured. A first series of animals received dexamethasone, triamcinolone or saline for 24 hrs, starting treatment 10 min after trauma. In a second series, steroid treatment lasted 48 hrs and in a third series the animals were additionally pretreated for 24 hrs. Dexamethasone and triamcinolone slightly decreased posttraumatic hemispheric swelling, from 7.7% in controls to 7.0% in treated animals. There was no significant difference between dexamethasone and triamcinolone. Reduction of swelling was most pronounced in animals with 48 hrs treatment. Pretreatment with steroids was not superior to early posttraumatic treatment. On the other hand, dexamethasone and triamcinolone significantly decreased cerebral water content in the traumatized and contralateral hemisphere, as well as in non-traumatized animals. The unspecific reduction of water content by steroids in rabbits might explain the moderate therapeutical effect on brain swelling. This effect might be beneficial, nevertheless, with respect to an improvement of the intracranial compliance.

Animals↗
PubMed1990

Electrical impedance, rCBF, survival and histology in Mongolian gerbils with forebrain ischaemia.

Survival, quantitative morphology of the hippocampus, cerebral tissue impedance and regional cerebral blood flow (rCBF) were studied in the Mongolian gerbil after 15 minutes of bilateral common carotid occlusion. A subgroup of animals was placed in cages with free access to running-wheels for two weeks preceding ischaemia to measure voluntary locomotor activity. Survival was enhanced in the running-wheel subgroup, with 90% of the animals still alive after 14 days as compared to 48% of the non-running group. Neuronal loss was found in all animals in the hippocampus (CA1, CA2, CA3 and CA4), and was most pronounced in the CA1 sector. In the running-wheel group, however, neuronal loss was significantly lower in sectors CA2, CA3 and CA4. The increases of cerebral impedance, which indicate ischaemic cell swelling, reached 190% in both groups during ischaemia. During postischaemic recirculation, however, impedance normalized more rapidly in the running-wheel group, indicating earlier resolution of ischaemic cell swelling. In wheel-running gerbils, postischaemic hyperperfusion evolved earlier and was more pronounced as compared to non-runners. No differences in systemic blood pressure were observed during cerebral ischaemia or thereafter.

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

Role of leukotrienes as mediator compounds in brain edema.

Leukotrienes accumulate in brain tissue after cerebral ischemia and in brain tumors. Thus, their release might contribute to the blood-brain barrier damage observed under these conditions and, hence, brain edema. The effect of these substances on the permeability of pial vessels and whether inhibition of LT synthesis reduces cold injury brain edema were studied. The pial vasculature of cats was studied by fluorescence microscopy. The cortex was superfused with LTC4, LTD4, or LTE4 via a cranial window. Na(+)-fluorescein was intravenously administered as blood-brain barrier indicator. LT concentrations up to 2 microM did not induce any leakage of the blood-brain barrier indicator into the parenchyma. However, all LTs tested constricted pial arteries and veins. Brain edema formation was studied in rabbits with cold injury. BW755C, an inhibitor of cyclooxygenase and lipoxygenase preventing formation of LTs, was given before and after trauma. Control animals received saline only. BW755C was ineffective in attenuating cold injury edema. Hemispheric swelling in control animals was 7.8 +/- 1.1%, and 7.7 +/- 0.4% in animals with treatment. LTs, even when administered to the brain in concentrations exceeding levels occurring under pathological conditions, did not induce barrier damage, nor did inhibition of LT synthesis attenuate formation of vasogenic edema. The results provide further evidence against LTs as mediator compounds of this process.

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

Blood-brain barrier permeability and vascular reactivity to bradykinin after pretreatment with dexamethasone.

The role of kinins as mediator substances is increasingly recognized in cerebral ischemia and trauma. It has previously been shown that cerebral exposure to bradykinin, which causes brain edema, is associated with arteriolar dilatation and selective opening of the blood-brain barrier (BBB) to small molecular weight indicators, such as Na+-fluorescein. Since the evidence suggests that these effects results from an activation of the arachidonic acid cascade, particularly from formation of E- and I-type prostaglandins, therapeutical inhibition of the cerebral effect of bradykinin has been attempted by pretreatment of experimental animals with dexamethasone. The BBB function and changes of the pial vessel diameters were studied by fluorescence microscopy in cats in alpha-chloralose anesthesia during superfusion of the exposed cerebral cortex. After a control phase bradykinin was added to a cerebral superfusate in concentrations of 4 x 10(-8) M to 4 x 10(-3) M. Two additional groups of animals received dexamethasone in a dose of 1, or 5 mg/kg body wt., respectively, 5 h prior to the cerebral superfusion with bradykinin. Na+-fluorescein (mol wt.: 376) was infused intravenously as a BBB indicator. The BBB marker remained strictly confined to the intravascular compartment under control conditions. Pretreatment with dexamethasone did not prevent opening of the BBB by bradykinin, either at the low, or high dose. However, the low dose of dexamethasone blunted the vasodilatory response to bradykinin, whereas the high dose (5 mg/kg) was found to enhance the dilatory properties of bradykinin at concentrations of 4 x 10(-3) M.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
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

Effects of free radicals on permeability and vasomotor response of cerebral vessels.

To obtain further evidence on the role of free radicals as mediators of secondary brain damage, blood-brain barrier (BBB) function and vasomotor response of pial vessels were studied during cortical superfusion of a free radical-generating system of xanthine-oxidase (XO) and hypoxanthine (HX). Intravenously administered Na+-fluorescein (mol. wt. 376), or fluorescein isothiocyanate (FITC)-dextran (mol. wt. 62,000) served as low- and high-molecular weight BBB indicators. Since undialyzed XO considerably increased the osmolarity of artificial cerebrospinal fluid, XO was subjected to equilibrium dialysis, which did not affect enzyme activity. Cortical superfusion with either HX (4 mM) or dialyzed XO alone (0.5 U/ml; osmolarity, 310 mosmol/l) did not induce a vasomotor response. Cortical superfusion with the free radical-generating system under normotonic conditions (HX plus dialyzed XO), led to moderate arterial dilation only with a maximum of +13%. The venous diameters remained unaffected. Moderate extravasation of the low molecular weight indicator Na+-fluorescein was seen in only 33% of the experiments, leakage of FITC-dextran was never observed. To assess the role of hypertonicity of the superfusate, the same experiments were performed with undialyzed XO. When superfusing the cortex with undialyzed XO (0.5 U/ml; osmolarity, 420 mosmol/l), the pial arteries dilated to 146%-168% of normal. Similarly, simultaneous superfusion with undialyzed XO (0.25 U/ml) and HX (2 mM) elicited arterial dilatation to 161%-178% of normal. Even the pial veins were significantly dilated to 108% of normal. In this series a moderate extravasation of Na+-fluorescein occurred in 75%, with leakage of FITC-dextran in 25%.(ABSTRACT TRUNCATED AT 250 WORDS)

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↗