Biomedical subjects

K A Hossmann

Publications and source records attributed to K A Hossmann.

At least 163 records · Page 9Linked to original sources

PubMed1992

Transglutaminase activity in human brain tumors.

Transglutaminase (TG) activity was measured in tissue samples of 45 human brain tumors (pituitary adenomas, meningiomas and gliomas) obtained during neurosurgery. Biochemical analysis and histopathological classification were carried out in the same samples. Mean enzyme activity was highest in non-glial tumors, but due to a high variability of values no significant changes were found between the various histological groups. Thus, TG activity, although considered to play a role in neoplastic growth, does not represent a biochemical marker of malignancy in human brain tumors.

Adenoma↗

PubMed1992

[Evoked potentials following cerebral ischemia in the rat: the effect of the stimulus frequency].

EEG and somatosensory evoked potentials were recorded in anesthetized rats before and up to 24 h after 30 min of global forebrain ischemia. Before ischemia, SEP (sweep time 1000 ms) included primary (N25P50) components and late potentials of low amplitude. During ischemia, SEP and EEG were isoelectric. During postischemic recirculation SEP evoked by stimulation at 1.0 Hz remained severely suppressed for 24 h, although long-latency potentials (> 100 ms) recovered. Using a very low stimulation frequency of 0.1 Hz, late components strongly increased in amplitude and the overall evoked activity in the averaged post-stimulus-EEG reached 90% of control. These results demonstrate that the SEP evoked at very low stimulation frequency may serve as an early indicator of functional brain recovery after prolonged cerebro-circulatory arrest.

Animals↗

PubMed1992

Activity of ornithine decarboxylase (ODC) and polyamine levels as biochemical markers of malignancy in human brain tumors.

The content of the polyamines putrescine, spermidine and spermine, and the activity of their metabolic key enzyme ornithine decarboxylase (ODC) were measured in tissue samples obtained during operation of 45 patients with primary or recurrent gliomas, meningiomas and pituitary adenomas. Biochemical analysis and histopathological classification were carried out in the same tumor samples. In benign tumors ODC activity was less than 10 nmol/g/h, whereas in malignant gliomas values up to 34 nmol/g/h were observed. In rapidly growing tumors pronounced heterogeneity was observed with high values in solid tumor parts and low values in necrotic areas. Thus, high ODC activity represents a reliable biochemical marker of malignancy in brain tumors, but low values do not prove benignity.

Adenoma↗

PubMed1991

Therapeutic window of halothane anesthesia for reversal of delayed neuronal injury in gerbils: relationship to postischemic motor hyperactivity.

The effect of postischemic halothane anesthesia on locomotor activity and delayed neuronal injury in the hippocampal CA1 sector was examined in gerbils subjected to 5-min forebrain ischemia. Locomotor activity was assessed for 48 h after ischemia using an animal activity monitor, and CA1 injury was evaluated by counting the number of surviving neurons following 7 days of recirculation. Sham-treated animals exhibited a slight decrease of motor activity for about 1 day after surgery. Gerbils subjected to ischemia without postischemic halothane anesthesia developed significant motor hyperactivity (18 times higher than control activity) between 1.7 h and 6.7 h of recirculation. Surviving CA1 neurons in this group amounted to only 17% of those in the control animals. Postischemic halothane anesthesia during the initial 1.7 h of recirculation abolished subsequent motor hyperactivity and protected 84% of all CA1 neurons. Postischemic halothane anesthesia during 1.7 h-3.3 h of recirculation and 3.3-5 h of recirculation did not abolish motor hyperactivity except during the period of anesthesia, and did not protect hippocampal CA1 neurons (only 24% and 10% neuronal survival, respectively). These results demonstrate that the therapeutic window of halothane anesthesia for protection of hippocampal injury precedes the phase of locomotor hyperactivity, and that the appearance of the latter predicts delayed neuronal death.

Anesthesia↗

PubMed1991

Locomotor hyperactivity and hippocampal CA1 injury after transient forebrain ischemia of gerbils.

The influence of a repeated transient forebrain ischemia on the development of post-ischemic locomotor hyperactivity was determined in the gerbil. Animals were subjected to two episodes of 5 min bilateral carotid artery occlusion in halothane anesthesia separated by one week. By using an animal activity monitor for counting spontaneous movements, the locomotor activity was assessed before and after each ischemic period. Seven days after ischemia the number of intact hippocampal CA1 neurons was counted from histological sections. Following the first 5 min ischemia a phase of locomotor hyperactivity of more than 20-fold of control was observed. One week after ischemia less than 20% of CA1 neurons had survived. Exposure of gerbils at this time to a second 5 min ischemic episode did not cause any increased locomotor activity. These findings support the assumption that post-ischemic locomotor hyperactivity is a symptom of the acutely injured but still functionally active CA1 sector of hippocampus.

Animals↗

PubMed1991

Two-stage resuscitation of the cat brain after prolonged cardiac arrest.

Following prolonged cardiac arrest, reperfusion of the brain is endangered by the low blood perfusion pressure during the early resuscitation phase. In order to avoid low perfusion brain injury, a two-stage resuscitation protocol was applied to cats submitted to 30 min potassium chloride induced cardiac arrest: first, the heart was resuscitated, followed--after stabilisation of blood pressure--by recirculation of the brain. During cardiac resuscitation the brain was disconnected from the general circulation by inflating a pneumatic cuff around the neck. The results were compared with the outcome of conventional one-stage resuscitation following 15 min cardiac arrest. Cardiac resuscitation was successful in 5 out of 8 animals with 15 min and in 6 out of 13 animals with 30 min cardiac arrest. In successfully resuscitated animals of both groups, brain energy metabolism recovered to normal within 3 h although two-stage resuscitation increased brain ischemia time to 37-61 min. Two-stage resuscitation, in consequence, is a promising approach for revival of the brain after prolonged cardiac arrest.

Adenosine Triphosphate↗

PubMed1991

Ischemic thresholds of cerebral protein synthesis and energy state following middle cerebral artery occlusion in rat.

The ischemic threshold of protein synthesis and energy state was determined 1, 6, and 12 h after middle cerebral artery (MCA) occlusion in rats. Local blood flow and amino acid incorporation were measured by double tracer autoradiography, and local ATP content by substrate-induced bioluminescence. The various images were evaluated at the striatal level in cerebral cortex by scanning with a microdensitometer with 75 microns resolution. Each 75 x 75 microns digitized image pixel was then converted into the appropriate units of either protein synthesis, ATP content, or blood flow. The ischemic threshold was defined as the flow rate at which 50% of pixels exhibited complete metabolic suppression. One hour after MCA occlusion, the threshold of protein synthesis was 55.3 +/- 12.0 ml 100 g-1 min-1 and that of energy failure was 18.5 +/- 9.8 ml 100 g-1 min-1. After 6 and 12 h of MCA occlusion, the threshold of protein synthesis did not change (52.0 +/- 9.6 and 56.0 +/- 6.5 ml 100 g-1 min-1, respectively) but the threshold of energy failure increased significantly at 12 h following MCA occlusion to 31.9 +/- 9.7 ml 100 g-1 min-1 (p less than 0.05 compared to 1 h ATP threshold value; all values are mean +/- SD). In focal cerebral ischemia, therefore, the threshold of energy failure gradually approached that of protein synthesis. Our results suggest that with increasing duration of ischemia, survival of brain tissue is determined by the high threshold of persisting inhibition of protein synthesis and not by the much lower one of acute energy failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1991

[14C]leucine incorporation into brain proteins in gerbils after transient ischemia: relationship to selective vulnerability of hippocampus.

Regional [14C]leucine incorporation into brain proteins was studied in gerbils after global ischemia for 5 min and recirculation times of 45 min to 7 days, using a combination of quantitative autoradiography and biochemical analysis. After recirculation for 45 min, incorporated radioactivity was reduced to approximately 20-40% of control values in all ischemic brain regions. Specific activity of the tracer, in contrast, was increased, a finding indicating that the reduced incorporation of radioactivity was not due to reduced tracer influx from plasma or a dilution of the tracer by increased proteolysis. After recirculation for 6 h, [14C]leucine incorporation returned to control levels in all regions except the CA1 sector of the hippocampus, where it amounted to less than 50%. After 1 day, protein synthesis in the CA1 sector returned to approximately 70% of control values, followed by a secondary decline to less than 50% after 3 days and returned to near control values after 7 days. Histological evaluations revealed selective neuronal death in the CA1 sector of the hippocampus after 3 days of recirculation. The complex time course of protein synthesis in the CA1 sector suggests a biphasic mode of injury, which may be related to similar changes of calcium homeostasis. The final return to near normal after CA1 neurons have disappeared is explained by astroglial proliferation and demonstrates that at this time protein synthesis is not a marker of neuronal viability.

Animals↗

PubMed1991

Cerebral polyamine metabolism in reversible hypoglycemia of rat: relationship to energy metabolites and calcium.

Thirty minutes of insulin-induced reversible hypoglycemic coma (defined in terms of cessation of EEG activity) was produced in anesthetized rats. At the end of the hypoglycemic coma or after recovery for 3, 24, or 72 h induced by glucose infusion, the animals were reanesthetized and their brains frozen in situ. Two control groups were used: untreated controls without prior manipulations, and insulin controls, which received injections of insulin followed by glucose infusion to maintain blood glucose within the physiological range. The brains of these latter animals were frozen 3, 24, or 72 h after glucose infusion. Tissue samples from the cortex, striatum, hippocampus, and thalamus were taken to measure ornithine decarboxylase (ODC) activity, and putrescine and spermidine levels, as well as phosphocreatine (PCr), ATP, glucose, and lactate content. In addition, 20-microns thick coronal sections taken from the striatum and dorsal hippocampus were used for histological evaluation of cell damage and also stained for calcium. Insulin in the absence of hypoglycemia produced a significant increase in ODC activity and putrescine level but had no effect on the profiles of energy metabolites or spermidine. During hypoglycemic coma, brain PCr, ATP, glucose, and lactate levels were sharply reduced, as expected. Energy metabolites normalized after 3 h of recovery. In the striatum, significant secondary decreases in PCr and ATP contents and rises in glucose and lactate levels were observed after 24 h of recovery. ODC activity, and putrescine and spermidine levels were unchanged during hypoglycemic coma. After 3 h of recovery, ODC activity increased markedly throughout the brain, except in the striatum. After 24 h of recovery, ODC activity decreased and approached control values 2 days later. Putrescine levels increased significantly throughout the brain after reversible hypoglycemic coma, the highest values observed after 24 h of recovery (p less than or equal to 0.001, compared with controls). After 72 h of recovery, putrescine levels decreased, but still significantly exceeded control values. Reversible hypoglycemic coma did not produce significant changes in regional spermidine levels except in the striatum, where an approximately 30% increase was observed after 3 and 72 h of recovery (p less than or equal to 0.01 and p less than or equal to 0.05, respectively). Twenty-four hours after hypoglycemic coma, intense calcium staining was apparent in layer III of the cerebral cortex, the lateral striatum, and the crest of the dentate gyrus. After 72 h of recovery, the intense calcium staining included also cortical layer II, the septal nuclei, the subiculum, and the hippocampal CA1-subfield.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

[Studies of experimental cerebral ischemia with NMR spectroscopy].

In vivo NMR (nuclear magnetic resonance) spectroscopy allows for non-invasive measurement of the intracellular pH and the concentration of different metabolites in defined areas of the brain. Phosphocreatine, ATP and lactic acid are of prime interest in ischaemia research. Moreover, a distinction can be made between glycolysis and the oxidative breakdown of glucose after administering C-13-labelled glucose. Finally, spectroscopy of fluorine-containing inert gases such as Freon-23 allows for measuring cerebral blood flow and for directly relating the metabolic alterations to the changes in cerebral blood flow. Given the non-invasive character of NMR spectroscopy all metabolic process occurring throughout one experiment can for the first time be followed up. Thus metabolic alterations during ischaemia can directly be correlated with post-ischaemic recovery processes. It has been shown with the cerebral ischaemia model in the cat that recovery after circulatory failure rather depends on post-ischaemic changes such as the recirculation rate or the speed of high-energy phosphate formation than on the speed of energy metabolism breakdown or acidosis occurring during ischaemia. The future of nuclear magnetic resonance spectroscopy in experimental ischaemia research certainly lies in the therapeutic range. As the exact extent of ischaemic damage can be determined in each experiment it is possible for the first time to define the effect of a drug substance on metabolic dysfunction in each individual experiment. This method is not only expected to reduce the number of laboratory animals but also to dramatically improve statistical variability compared to group comparisons.

Animals↗

PubMed1990

Magnetic resonance imaging and regional biochemical analysis of experimental brain tumours in cats.

Multiexponential evaluation of in vivo multi-echo T2 measurements at 4.7T in cat brain with implanted tumour led to monoexponential results in all tissues. T2 of normal brain tissue, tumour and oedema was 67 ms, 10-100 ms and 90-180 ms, respectively. In the ventricles biexponential solutions were observed with T2 values and relative contributions of these two components differing for ipsi- and contralateral side. Best discrimination between tumour and oedema was achieved by the magnetization value M (O), and between oedema and normal brain tissue by T2. T2 values were compared with in vitro biochemical analyses for ATP, lactate, glucose, tissue electrolytes and water content. NMR parameters provide reliable predictions about the water content and metabolic state of oedema, but not of the tumour.

Adenosine Triphosphate↗

PubMed1990

MRI contrast enhancement by MnTPPS of experimental brain tumours in rats.

In the experimental F98 rat glioma model the nuclear magnetic resonance contrast agent MnTPPS was used to increase the contrast between tumour and peritumourous brain tissue. By evaluating pre- and postcontrast CPMG echo trains after different dose and circulation times of MnTPPS, the transverse relaxation time T2, the magnetization extrapolated to the time zero M (0), and the contrast ratio Rc of the magnetizations in neoplastic and normal tissues were determined. According to these data a maximum contrast is obtained a few hours after injection of 0.25 mmol MnTPPS/kg bw, using spin echo pulse sequences with short repetition times TR (1,100 ms), and short spin echo time TE (25 ms).

Animals↗

PubMed1990

Relationship between cerebral blood flow and blood-brain barrier permeability of sodium and albumin in cerebral infarcts of rats.

The permeability of the blood-brain barrier to sodium and albumin was investigated in rats following occlusion of the middle cerebral artery. Regional blood flow and unidirectional transfer coefficients of sodium and albumin were measured by triple tracer autoradiography, and tissue electrolyte content by atomic absorption spectroscopy. In sham-operated controls regional transfer coefficients of sodium ranged between 1.3 and 3.2 x 10(-3) ml.g-1.min-1; the transfer coefficient of albumin was below the detection limit of autoradiography. During the initial 4h of vascular occlusion neither albumin nor sodium permeability changed although tissue sodium content increased from 56 +/- 3 to 76 +/- 8 mumol.g-1. After 24 h transfer coefficient of sodium rose to between 2.91 and 7.0 x 10(-3) ml.g-1.min-1, and tissue sodium content to 90 +/- 9 mumol.g-1. Despite this rise the net uptake rate of sodium was 4 to 60 times lower than the unidirectional influx, indicating that permeability changes of the blood-brain barrier are without relevance for the development of stroke oedema.

Animals↗

PubMed1990

Relationship between of blood flow, glucose metabolism, protein synthesis, glucose and ATP content in experimentally-induced glioma (RG1 2.2) of rat brain.

In experimental RG1 2.2 glioma of rat brain, local blood flow, glucose utilization, protein synthesis, glucose and ATP content were measured by means of triple tracer autoradiography and bioluminescence technique, respectively, to determine hemodynamic and metabolic thresholds for local tumor energy failure. Perfusion thresholds were estimated at tumor blood flow values of 69.0 +/- 0.1 ml/100 g/min (estimate +/- standard error) and of 69 +/- 7.1 ml/100 g/min for the beginning of the decline in regional ATP and glucose content, respectively. Metabolic thresholds were derived at tumor glucose utilization values of 70.6 +/- 8.3 mumol/100 g/min for reduced protein synthesis, of 55.0 +/- 0.2 mumol/100 g/min for the decrease in glucose content, and 34.7 +/- 4.7 mumol/100 g/min for decline in ATP content. Our results suggest that blood flow limits glucose supply to tumor tissue at much higher flow rates than in normal brain which, in turn, is associated with a decrease in tumor glucose utilization. A reduction and not an increase in tumor glucose availability could be a more appropriate strategy for the induction of energy failure in tumors.

Adenosine Triphosphate↗

PubMed1990

Selective vulnerability in the gerbil hippocampus: morphological changes after 5-min ischemia and long survival times.

The morphology of the hippocampus of Mongolian gerbils was investigated by light and electron microscopy after 5-min forebrain ischemia and survival times of up to 10 months. After 3 weeks recirculation only 5.8% of pyramidal neurons of the CA1 (cornu ammonis 1) sector had survived but the thickness of the inner and outer hippocampal layers did not change. After recirculation times of 6 and 10 months the number of surviving neurons declined no further but all layers of the CA1 subfield shrank markedly. Ultrastructurally, many but not all surviving CA1 neurons were altered. After 3 weeks both "dark" and "pale" type neurons were present, while after 6 and 10 months only the "pale" type of injury persisted. Axonal enlargements and myelin breakdown were observed at all survival times up to 10 months of recirculation. The astrocytes of CA1 sector contained numerous glial fibrils which were most pronounced after the longer recirculation times. The stratum radiatum presented intact presynaptic terminals densely packed with an abundance of clear vesicles even after survival of 10 months. Initially, morphologically damaged postsynaptic structures were still attached to these terminals but they disappeared after longer recirculation times. However, even after 10 months some intact synapses were observed involving dendrites which probably originated from surviving CA1 neurons. In CA3 sector and dentate gyrus no ultrastructural changes occurred at any survival time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Pattern of neuronal vulnerability in the cat hippocampus after one hour of global cerebral ischemia.

The dorsal hippocampus of cat was investigated by light microscopy and immunohistochemistry following 1 h global cerebral ischemia and various recirculation times from 1 day to 1 year. Complete ischemia was produced by combining hypotension with intrathoracic occlusion of major arteries. Post-ischemic resuscitation was carried out using an intensive care regimen with continuous neurophysiological monitoring. Brains of controls (n = 4) and post-ischemic animals (n = 12) were fixed in formaldehyde and prepared for histology and immunohistochemistry of glial fibrillary acidic protein (GFAP). In all post-ischemic animals the hilus and the regio superior of dorsal hippocampus which encompasses the CA1 subfield were severely damaged. Neurons in these regions exhibited the typical sequela of neuronal death. GFAP staining revealed vivid astroglial proliferation in stratum lacunosum-moleculare and stratum oriens. Changes in the regio inferior of dorsal hippocampus, i.e., CA3 subfield, and in dentate gyrus granular layer, were variable. Although most animals exhibited moderate to severe neuronal and glial alterations, groups of surviving cells were observed in the stratum oriens and in the granular layer of dentate gyrus. In one animal the majority of CA3 pyramidal cells and granule cells was preserved. These findings demonstrate that after 1 h of complete cerebral ischemia dorsal hippocampus exhibits two different types of injury: a consistent pattern of selective vulnerability in the hilus and the regio superior, and a variable pattern of non-selective injury in the regio inferior and dentate gyrus. The two patterns can be best explained by intrinsic (pathoclitic) and extrinsic (hemodynamic/edema) factors, respectively and are likely to represent basically different mechanisms of ischemic injury.

Animals↗

PubMed1990

Determination of endogenous serum proteins in normal and oedematous brain tissue of cat by rocket and crossed immunoelectrophoresis.

A quantitative method for determination of endogenous serum proteins has been established and tested in an experimental model of peritumoural brain oedema in cats. Rocket and crossed immunoelectrophoresis were applied for determination of total serum proteins, albumin, IgG and haemoglobin in blood and brain homogenates. Modifications such as the use of non-ionic detergents and of antisera with different specificity were established for each antigen under investigation. The content of total serum proteins, albumin and IgG was substantially higher in tumour and peritumoural brain tissue than in the non-oedematous brain. The measurement of haemoglobin allowed the calculation of blood volume and, in consequence, the differentiation between intra- and extravascular serum proteins. The results are in line with earlier measurements obtained by different analytical methods and demonstrate that the present technique provides a reliable approach for the quantitative assessment of serum protein extravasation.

Animals↗

PubMed1990

Putrescine content and structural defects in isolated fractions of rat brain after reversible cerebral ischemia.

Reversible cerebral ischemia was produced in rats by occluding both vertebral and both carotid arteries. Following 30 min of ischemia, brains were recirculated for 24 h. The hippocampus, the striatum, and the cortex were sampled, homogenized, and fractionated on a discontinuous sucrose gradient. The fractions were evaluated morphologically by electron microscopy and biochemically by measuring the activity of marker enzymes. Putrescine was extracted from the isolated fractions and measured quantitatively using HPLC and a fluorescence detector. In the total tissue homogenate of control animals putrescine content amounted to 72.0 +/- 3.1, 70.2 +/- 7.6, and 72.7 +/- 2.1 pmol/mg protein in samples prepared from the cortex, the hippocampus, and the striatum, respectively. In the mitochondrial fraction the content was lower, while in the synaptosomal fraction and in myelin it was higher than that in total tissue homogenate. Following cerebral ischemia there was a 6- to 10-fold increase in putrescine in tissue homogenate: In the cortex it increased to 429 +/- 24 pmol/mg protein, in the hippocampus to 585 +/- 70 pmol/mg protein, and in the striatum to 718 +/- 98 pmol/mg protein. Among the isolated fractions the highest levels of putrescine were found in synaptosomes from the striatum (663 +/- 196 pmol/mg protein), followed by the hippocampus (500 +/- 125 pmol/mg protein) and the cerebral cortex (349 +/- 45 pmol/mg protein). This order correlated to the degree of morphological injury which was most pronounced in the striatum and the hippocampus and less in the cerebral cortex. The results of the present study provide further evidence of a relationship between postischemic putrescine levels and the extent of ischemia-induced neuronal injury.

Animals↗