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Biomedical subjects

M Kiessling

Publications and source records attributed to M Kiessling.

At least 73 records · Page 4Linked to original sources
PubMed1992

Induction of immediate early gene encoded proteins in the rat hippocampus after bicuculline-induced seizures: differential expression of KROX-24, FOS and JUN proteins.

Immunocytochemistry with specific antisera was used to assess regional levels of six immediate early gene encoded proteins (KROX-24, c-FOS, FOS B, c-JUN, JUN B and JUN D) in the rat hippocampus after 15 min of bicuculline-induced seizures. Serial sections of the dorsal hippocampus were examined at various postictal recovery periods up to 24 h. The results demonstrate a complex temporal and spatial pattern of immediate early gene synthesis and accumulation. Three major categories of immediate early gene products could best be distinguished in the dentate gyrus: KROX-24 and c-FOS showed a concurrent rapid rise with peak levels at 2 h and a return to baseline levels within 8 h after seizure termination. FOS B, c-JUN and JUN B levels increased more gradually with peak intensities in the dentate gyrus reached at 4 h. These immediate early gene products showed above normal levels in various hippocampal subpopulations up to 24 h. JUN D exhibited the most delayed onset combined with a prolonged increase of seizure-induced immunoreactivity. Irrespective of this differential temporal expression profile of individual transcription factors, the sequence of induction in the hippocampal subpopulations was identical for all immediate early gene-encoded proteins examined: first in the dentate gyrus granule cells followed by CA1 and CA3 neurons, respectively. Our data indicate an asynchronous synthesis of several immediate early gene-encoded proteins in the brain after status epilepticus. FOS and JUN proteins act via homo- or heterodimer complexes at the AP-1 and other DNA binding sites. The different time-courses for individual immediate early gene products strongly suggest, that at different time-points after status epilepticus, different AP-1 complexes are effective. In vitro studies have shown that different AP-1 complexes possess different DNA binding affinities as well as different transcriptional regulatory effects. Our results suggest that these molecular mechanisms are also effective in vivo.

Animals↗
PubMed1991

Three-dimensional time-of-flight MR-angiography and the surgical indication of brainstem cavernomas.

This study was designed to assess the diagnostic value of 3D time-of-flight MR-angiography in cerebral cavernomas. In seven patients, nine out of ten cavernomas were removed by microsurgery. While MR-angiography demonstrated well branches of brain arteries adjacent to the lesions, no flow signal in the vascular malformations was observed. On the other hand, there was a high intensity signal induced by methaemoglobin in those three patients with brainstem cavernomas who had experienced a significant bleeding attack seven months prior to admission. It had a spotted appearance in MR-angiography with volumes of the largest spots around 1.8 cm3. It is suggested that this spot signal could be used as a path marker for the surgical approach in brainstem cavernomas.

Adult↗
PubMed1990

Glucocorticoid therapy obscures the diagnosis of cerebral lymphoma.

Neuropathological and radiographical findings of two patients with primary CNS B cell lymphoma are presented. Prior to computerized tomographic (CT)-guided stereotactic biopsy both patients had received glucocorticoid therapy which led to marked tumor regression on CT scans and transient improvement of neurological deficits. Despite careful targeting and serial sampling, multiple biopsy specimens examined cytologically, histologically and immunomorphologically showed nonspecific reactive astrogliosis and conspicuous perivascular infiltrates of T lymphocytes. A second biopsy performed after an interval of 2 and 8 weeks, respectively, and short-term discontinuation of dexamethasone therapy in one case, unequivocally established the diagnosis of Non-Hodgkin lymphoma. It is concluded that steroid therapy may obscure the bioptic diagnosis of cerebral lymphoma. In addition to the well-known antiedematous effect of glucocorticoids neuropathologists and neurosurgeons should be aware of a rapid and pronounced lymphodepletive action of steroids on malignant CNS lymphomas.

Astrocytes↗
PubMed1990

Cerebrovascular and metabolic effects on the rat brain of focal Nd:YAG laser irradiation.

To investigate the effects of focal neodymium:yttrium-aluminum-garnet (Nd:YAG) laser irradiation (lambda = 1060 nm) on regional cerebral blood flow, cerebral protein synthesis, and blood-brain barrier permeability, the parietal brain surface of 44 rats was irradiated with a focused laser beam at a constant output energy of 30 J. Survival times ranged from 5 minutes to 48 hours. Laser irradiation immediately caused well-defined cortical coagulation necrosis. Within 5 minutes after unilateral irradiation, 14C-iodoantipyrine autoradiographs demonstrated severely reduced blood flow to the irradiation site and perilesional neocortex, but a distinct reactive hyperemia in all other areas of the forebrain. Apart from a persistent ischemic focus in the vicinity of the cortical coagulation necrosis, blood flow alterations in remote areas of the brain subsided within 3 hours after irradiation. Autoradiographic assessment of 3H-tyrosine incorporation into brain proteins revealed rapid onset and prolonged duration of protein synthesis inhibition in perifocal morphologically intact cortical and subcortical structures. Impairment of amino acid incorporation proved to be completely reversible within 48 hours. Immunoautoradiographic visualization of extravasated plasma proteins using 3H-labeled rabbit anti-rat immunoglobulins-showed that, up to 1 hour after irradiation, immunoreactive proteins were confined to the neocortex at the irradiation site. At 4 hours, vasogenic edema was present in the vicinity of the irradiation site and the subcortical white matter, and, at later stages (16 to 36 hours), also extended into the contralateral hemisphere. Although this was followed by a gradual decrease in labeling intensity, resolution of edema was still not complete after 48 hours. Analysis of sequential functional changes in conjunction with morphological alterations indicates that the evolution of morphological damage after laser irradiation does not correlate with the time course and spatial distribution of protein synthesis inhibition or vasogenic edema. Although the central coagulation necrosis represents a direct effect of radiation, the final size of the laser-induced lesion is determined by a delayed colliquation necrosis due to persistent perifocal ischemia. Extent and severity of ischemia in a zone with initial preservation of neuroglial cells can be explained by the optical properties of the Nd:YAG laser; extensive scattering of light within brain parenchyma associated with a high blood-to-brain absorption ratio selectively affects blood vessels outside the irradiation focus.

Amino Acids↗
PubMed1988

Blood flow and metabolism in heterotopic cerebellar grafts during hypoglycemia.

Hypoglycemia-induced disturbances of brain metabolism and neuronal injury exhibit a distinct predilection for forebrain structures, in particular the caudate-putamen, hippocampus and cerebral cortex, whereas the cerebellum is remarkably resistant. In an attempt to assess the biological basis of this differential regional vulnerability, we have used a neural transplantation technique to compare hemodynamic and metabolic changes in cerebellum during severe hypoglycemia with those in heterotopic cerebellar grafts. To this end, the cerebellar anlage of fetal rat brain (day 15 of gestation) was stereotactically transplanted into the vulnerable caudate-putamen. Following a differentiation period of 8 weeks the grafts had developed into an organotypic population of mature cells with laminar histoarchitecture. Host animals were then subjected to insulin-induced hypoglycemia. After 15 min of isoelectric EEG, blood flow was increased throughout the brain but residual glucose consumption was significantly higher in cerebellum (0.29 mumol/g per min) and cerebellar grafts (0.22 mumol/g per min) as a result of increased glucose extraction. Hypoglycemia caused a depletion of ATP in all brain structures except cerebellum where normal levels were maintained. Correlation of local ATP content and glucose utilization revealed a threshold-like decline of ATP at a glucose utilization rate of 0.27 mumol/g per min. ATP, in consequence, was normal in cerebellum but partially depleted in cerebellar grafts. It is concluded that the resistance of cerebellum to hypoglycemia is due to its capacity for higher glucose extraction at low blood glucose levels, and that this unique intrinsic property is preserved after heterotopic transplantation.

Adenosine Triphosphate↗
PubMed1988

Focal brain ischemia in the rat: methods for reproducible neocortical infarction using tandem occlusion of the distal middle cerebral and ipsilateral common carotid arteries.

This article describes a 3-year experience with focal neocortical ischemia in three rat strains. Multiple groups of adult Wistar (n = 50), Fisher 344 (n = 31), and spontaneously hypertensive (n = 72) rats were subjected to permanent occlusion of the distal middle cerebral (MCA) and ipsilateral common carotid arteries (CCA). Twenty-four hours later the animals were killed, and frozen brain sections were stained with hematoxylin and eosin to demarcate infarcted tissue. The infarct volume for each section was quantified with an image analyzer, and the total infarct volume was calculated with an iterative program that summed all interval volumes. Neocortical infarct volume was the largest and most reproducible in the spontaneously hypertensive rats (SHR). Statistical power analysis to project the numbers of animals necessary to detect a 25 or 50% change in infarct volume with alpha = 0.05 and beta = 0.2 revealed that only the SHR model was practical in terms of requisite animals: i.e., less than 10 animals per group. Tandem occlusion of the distal MCA and ipsilateral CCA in the SHR strain provides a surgically simple method for causing large neocortical infarcts with reproducible topography and volume. The interanimal variability in infarct volume that occurs even in the SHR strain dictates that randomized, concomitant controls are necessary in each study to ensure the accurate assessment of experimental manipulations or pharmacologic therapies.

Animals↗
PubMed1986

Resistance to hypoglycemia of cerebellar transplants in the rat forebrain.

Prolonged insulin-induced hypoglycemia causes widespread loss of neurons and permanent brain damage with irreversible coma. Although the deprivation of carbohydrate stores affects all brain regions, the breakdown of energy metabolism and cessation of protein synthesis occur predominantly in the cerebral cortex, caudoputamen and hippocampus. The cerebellum, brain stem and hypothalamus are largely resistant. Following transplantation of the cerebellar anlage of rat fetuses (day 15 of gestation) into the caudoputamen of adult rats, the grafts were allowed to differentiate for a period of 8 weeks. The host animals were then subjected to 30 min of severe hypoglycemia with isoelectric EEG ('coma'). In contrast to the surrounding vulnerable brain structures, protein synthesis was fully preserved within the cerebellar transplant. Grafting of fetal forebrain cortex to the same location did not result in escape from hypoglycemic cell injury. This indicates that resistance to hypoglycemia is part of the programmed differentiation of the cerebellum and develops irrespective of its location and functional integration within the nervous system.

Animals↗
PubMed1986

Persistent inhibition of protein synthesis precedes delayed neuronal death in postischemic gerbil hippocampus.

Regional cerebral protein synthesis was investigated in the Mongolian gerbil during recovery from forebrain ischemia produced by bilateral common carotid artery occlusion for 5 min. At various recirculation periods up to 72 h animals received a single dose of L-(3,5-3H)tyrosine and were killed 30 min later. Brains were processed for autoradiography using the stripping film technique. During the initial 30 min of recirculation autoradiographs revealed an almost complete inhibition of protein synthesis in all forebrain structures with the exception of the medio-dorsal thalamic nuclei. Between 30 min and 12 h of recirculation amino acid incorporation was completely restored in neurons of the cerebral cortex, basal ganglia, hippocampal CA3 and CA4 zones and the dentate gyrus. In CA1, early (90-min postischemia) and progressive recovery of a few irregularly dispersed neurons was observed, but the vast majority of pyramidal cells never regained their normal biosynthetic activity. Between 3 and 6 h of recirculation CA1 neurons showed faint labeling, followed by a secondary deterioration resulting in complete lack of incorporation within 12 h after restoration of blood flow. Autoradiographs at all subsequent time points exhibited persistent inhibition of protein synthesis in CA1 until neuronal necrosis occurred 2-3 days later. Thus, in contrast to ischemia-resistant cell populations with rapid progressive and complete restoration of protein synthesis, hippocampal neurons undergoing delayed necrosis are characterized by an early incomplete recovery immediately followed by a secondary persistent inhibition.

Animals↗
PubMed1986

Protein synthesis in postischemic rat brain: a two-dimensional electrophoretic analysis.

This study examined the pattern of protein synthesis in the neocortex, caudate-putamen, and the hippocampus following transient forebrain ischemia in rats. The animal model of temporary ischemia used in this study causes permanent damage to vulnerable neurons with a time course of injury that varies from hours (caudate nucleus) to days (hippocampus). To examine the spectrum of proteins synthesized in these regions at 3 and 18 h after recirculation, cerebral proteins were pulse-labeled in vivo by an intravenous injection of [35S]methionine. Newly synthesized (35S-labeled) and constitutive (unlabeled) proteins were analyzed by two-dimensional gel electrophoresis and fluorography. In all three brain regions, specific proteins underwent preferential synthesis (Mr approximately 27,000, approximately 65,000, approximately 70,000, approximately 110,000), while others showed decreased synthesis (neuron-specific enolase, alpha- and beta-tubulin). There was an early (3 h post ischemia) induction of the Mr approximately 70,000 mammalian "stress" protein; at 18 h post ischemia, its synthesis remained high in the hippocampus but was diminished in the neocortex and had largely subsided in the caudate-putamen. All regions at 18 h showed increased synthesis of an Mr approximately 50,000 protein, tentatively identified as glial fibrillary acidic protein. The results show that temporary forebrain ischemia induces changes in protein synthesis that include features similar to those observed in other eukaryotic cells subjected to injurious stress. These postischemic changes in protein synthesis are qualitatively similar in all brain regions examined despite regional differences in the severity of subsequent neuronal damage. The persistent synthesis of the Mr approximately 70,000 stress protein in the hippocampus, however, may reflect continued metabolic injury long after the ischemic episode has passed.

Animals↗
PubMed1986

Selective gene expression in focal cerebral ischemia.

Regional patterns of protein synthesis were examined in rat cortex made ischemic by the occlusion of the right common carotid and middle cerebral arteries. At 2 h of ischemia, proteins were pulse labeled with intracortical injections of a mixture of [3H]leucine, [3H]isoleucine, and [3H]proline. Newly synthesized proteins were analyzed by two-dimensional gel fluorography, and the results correlated with local CBF, measured with [14C]iodoantipyrine as tracer. Small blood flow reductions (CBF = 50-80 ml 100 g-1 min-1) were accompanied by a modest inhibition in synthesis of many proteins and a marked increase in one protein (Mr 27,000). With further reduction in blood flow (CBF = 40 ml 100 g-1 min-1), synthesis became limited to a small group of proteins (Mr 27,000, 34,000, 73,000, 79,000, and actin) including two new polypeptides (Mr 55,000 and 70,000). Severe ischemia (CBF = 15-25 ml 100 g-1 min-1) caused the isoelectric modification of several proteins (Mr 44,000, 55,000, and 70,000) and induced synthesis of another protein (Mr 40,000). Two polypeptides (Mr 27,000 and 70,000) dominated residual protein synthesis in severe ischemia. The changes in protein synthesis induced by different grades of ischemia most likely comprise a variation of the so-called "heat shock" or "stress" response found in all eukaryotic cells subjected to adverse conditions. Since heat shock genes are known to confer partial protection against anoxia and a variety of other noxious insults, their induction may be a factor in limiting the extent of ischemic tissue damage.

Animals↗
PubMed1986

Cerebral protein synthesis during long-term recovery from severe hypoglycemia.

Regional protein synthesis was investigated in the rat brain during long-term recovery from insulin-induced hypoglycemia with 30 min of cerebral electrical silence. At various time intervals up to 14 days after glucose replenishment, animals received a single dose of L-[3,5-3H]tyrosine and were killed 30 min later. Brains were processed for autoradiography using the stripping film technique. Although hypoglycemia sufficiently severe to cause cessation of EEG activity leads to almost complete inhibition of amino acid incorporation in all "vulnerable" forebrain structures (cerebral cortex, hippocampus, caudoputamen), autoradiographs revealed a very specialized sequence with differential posthypoglycemic restoration of biosynthetic activity in certain neuronal cell types. Three major subpopulations could be distinguished: Neurons that fully regained their protein synthetic capacity within 6 h following hypoglycemia (cortical neurons of layer III-VI, large neurons in the caudoputamen, CA3 and CA4 pyramidal neurons, the majority of granule cells of the dentate gyrus) seemed to escape neuronal necrosis. Prolonged impairment of protein synthesis with only partial restoration during the early posthypoglycemic recovery period (CA1 neurons, most small- to medium-sized neurons of the caudoputamen) carried an increased risk of permanent cell damage. The large majority of these neurons, however, showed full recovery of protein synthesis as late as 7 days after hypoglycemia. Neurons with complete lack of amino acid incorporation after 6 h of recovery (granule cells at the crest of the dentate gyrus, small neurons of the dorsolateral caudoputamen) never resumed protein synthesis, regressed, and died. These studies in conjunction with morphological analysis indicate that the sequential recovery of protein synthesis reflects the extent to which neuronal populations are at risk during severe hypoglycemia.

Animals↗
PubMed1986

Synthesis of heat shock proteins in rat brain cortex after transient ischemia.

Cell-free protein synthesis and two-dimensional gel autoradiography were used to characterize early postischemic protein synthesis in rat neocortex. Severe forebrain ischemia was induced for 30 min (four-vessel occlusion model) and followed by 3 h of recirculation. Polysomes were isolated from the cerebral cortex, translated in vitro in a reticulocyte system, and analyzed by two-dimensional gel electrophoresis. The translation products of postischemic polysomes included a major new protein family (70 kDa) with multiple isoelectric variants that was found to comigrate with the 68- to 70-kDa "heat shock" protein synthesized from polysomes of hyperthermic rats. Two other stress proteins (93 and 110 kDa) also appeared to be synthesized in increased amounts after ischemia. A complement of proteins that was indistinguishable from that of controls was also synthesized after ischemia, indicating that messenger ribonucleic acid coding for most brain proteins is preserved after ischemia and is bound to polysomes.

Animals↗
PubMed1985

Time course and spatial distribution of neodymium: yttrium-aluminum-garnet (Nd:YAG) laser-induced lesions in the rat brain.

Cerebral lesions made by focal neodymium:yttrium-aluminum-garnet (Nd:YAG) laser irradiation of the rat forebrain were studied in adult Wistar rats. For the analysis of time-dependent changes, the brains of 28 animals were irradiated with a constant energy density of 461 J/cm2. In this series, survival time ranged from 0.5 hours to 80 days. Immediately after irradiation, a circular lesion appeared on the surface of the brain. This lesion was surrounded by an edematous area intensively stained with Evans blue. At energy levels higher than 30 J, this circular edema contained numerous thrombosed vessels. Histopathologically, the lesion consisted of three distinct zones: the central coagulation necrosis was surrounded by a zone of delayed colliquation necrosis and by perifocal edema. At approximately 80 days after irradiation, the resulting cortical defect was covered by a pial membrane. Edematous changes of the brain cortex and the adjacent white matter were observed as early as 1 hour after irradiation. Within 16 hours, the perifocal edema spread over the white matter of both hemispheres, and it had disappeared by the 5th day after irradiation. In a second experiment, the energy density varied from 231 to 3077 J/cm2. This series consisted of 84 animals that were allowed to survive 48 hours. The size of the lesion depended on the level of energy applied, but the depth of the lesion varied less than the diameter at the brain surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗