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R Schmidt-Kastner

Publications and source records attributed to R Schmidt-Kastner.

At least 55 records · Page 3Linked to original sources
PubMed1991

Damage of substantia nigra pars reticulata during pilocarpine-induced status epilepticus in the rat: immunohistochemical study of neurons, astrocytes and serum-protein extravasation.

The substantia nigra has a gating function controlling the spread of epileptic seizure activity. Additionally, in models of prolonged status epilepticus the pars reticulata of substantia nigra (SNR) suffers from a massive lesion which may arise from a massive metabolic derangement and hyperexcitation developing in the activated SNR. In this study, status epilepticus was induced by systemic injection of pilocarpine in rats. The neuropathology of SNR was investigated using immunohistochemical techniques with the major emphasis on the time-course of changes in neurons and astrocytes. Animals surviving 20, 30, 40, 60 min, 2, 3, 6 hours, 1, 2, and 3 days after induction of status epilepticus were perfusion-fixed, and brains processed for immunohistochemical staining of SNR. Nissl-staining and antibodies against the neuron-specific calcium-binding protein, parvalbumin, served to detect neuronal damage in SNR. Antibodies against the astroglia-specific cytoskeletal protein, glial fibrillary acidic protein (GFAP), and against the glial calcium-binding protein, S-100 protein, were used to assess the status of astrocytes. Immunohistochemical staining for serum-albumin and immunoglobulins in brain tissue was taken as indicator of blood-brain barrier disturbances and vasogenic edema formation. Immunohistochemical staining indicated loss of GFAP-staining already at 30 min after induction of seizures in an oval focus situated in the center of SNR while sparing medial and lateral aspects. At 1 h there was additional vacuolation in S-100 protein staining. By 2 hours, parvalbumin-staining changed in the central SNR indicating neuronal damage, and Nissl-staining visualized some neuronal distortion. Staining for serum-proteins occurred in a patchy manner throughout the forebrain during the first hours. By 6 h, vasogenic edema covered the lesioned SNR. By 24 h, glial and neuronal markers indicated a massive lesion in the center of SNR. By 48-72 h, astrocytes surrounding the lesion increased in size, and polymorphic phagocytotic cells invaded the damaged area. In a further group of animals surviving 1 to 5 days, conventional paraffin-sections confirmed the neuronal and glial damage of SNR. Additional pathology of similar quality was found in the globus pallidus. Since astrocytes were always damaged in parallel with neurons in SNR it is proposed that the anatomical and functional interrelationship between neurons and astrocytes is particularly tight in SNR. Both cell elements may suffer in common from metabolic disturbance and neurotransmitter dysfunction as occur during massive status epilepticus.

Animals↗
PubMed1990

Transglutaminase activity in reversible cerebral ischemia in the rat.

Transglutaminase (TG, EC 2.3.2.13) activity and levels of putrescine (a natural acyl-acceptor in the transglutaminase reaction) were measured in rat brains after 30 min ischemia and 8 or 24 h recirculation. TG activity was significantly increased in the striatum and hippocampus already during cerebral ischemia and, more pronounced, after 8 and 24 h recirculation. In the cortex, in contrast, TG activity did not change during ischemia and 8 h recirculation but was significantly increased after 24 h recirculation. Putrescine levels were sharply increased after 8 h recirculation and even further after 24 h recirculation. It is suggested that in vivo during ischemia and early recirculation, when cells are overloaded with calcium ions, a pathological increase in the TG-catalyzed cross-linking of proteins may be apparent especially in the nerve endings of the hippocampus where the intrinsic concentration of the acyl-donor (protein-bound glutamyl-moiety) has been shown to be high.

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

Immunohistochemical study of glial reaction and serum-protein extravasation in relation to neuronal damage in rat hippocampus after ischemia.

Transient forebrain ischemia of 30 min duration was produced in anaesthetized rats by four-vessel occlusion. After survival periods of 3 h to three days brains were perfusion-fixed and sections through the mid-dorsal hippocampus were processed for conventional staining and immunohistochemical analysis. Neuronal damage in the hilus was manifested 3-8 h after ischemia; neurons in the CA1 and CA2 sector suffered delayed neuronal death after 48-72 h whereas the dentate gyrus and the CA3 sector were normal. Vasogenic edema formation was visualized using antibodies against rat serum-proteins, serum albumin and immunoglobulins. By 3 h after ischemia, only faint and diffuse serum-staining was detected. At 8 h survival, weak astrocytic-staining was present. After 24-72 h CA1-CA2 exhibited massive serum extravasation. The molecular layer of the dentate gyrus showed edema formation in the absence of granule cell damage. The glial reaction was studied using antibodies against glial fibrillary acidic protein, vimentin and S-100 protein. Glial fibrillary acidic protein and S-100 protein-staining increased in areas with either edema or neuronal damage. In contrast, changes in vimentin were only detected in areas with neuronal necrosis. The observations demonstrate that following 30 min of ischemia neuronal damage is accompanied by changes in blood-brain barrier function and reactive glial alterations. The dissociation between neuronal necrosis and astroglial hypertrophy and hyperplasia reflects differences in cellular responsiveness which constitute inherent features of postischemic hippocampal injury.

Animals↗
PubMed1989

A modified four-vessel occlusion model for inducing incomplete forebrain ischemia in rats.

The four-vessel occlusion (4VO) model of Pulsinelli and Brierley (Stroke 1979;10:267-272) has been modified for use in halothane-nitrous oxide-anesthetized, physiologically controlled rats that were ventilating spontaneously. Selection criteria for the classification of severity of ischemia were established by correlating changes in the electroencephalogram and the general physiological status with measurements of regional blood flow and regional energy metabolism. In 13% of animals, 4VO did not cause flattening of the electroencephalogram, and such animals were classified as undergoing only "oligemia." In 65% of rats, the electroencephalogram flattened and blood pressure sharply increased with 4VO, whereas spontaneous respiration continued. This group exhibited almost complete ischemia in autoradiographic blood-flow studies, severe acidosis, and depletion of adenosine 5'-triphosphate and glucose in the forebrain and, hence, was classified as the "ischemia" group. The remaining 22% stopped breathing after vascular occlusion and were rejected for further study. Survival experiments of ischemic animals revealed the typical postischemic sequelae, with primary metabolic recovery after 8 hours of recirculation in all brain structures followed after 8-24 hours by severe biochemical deterioration and neuronal death in the striatum and hippocampus. Postischemic seizure activity was rare. The main advantages of the present modification in comparison with the original method are 1) the application of anesthesia without loss of primary selection criteria, 2) the possibility of invasive physiological monitoring, and 3) the absence of postischemic seizures, which eliminates the necessity for secondary selection criteria.

Adenosine Triphosphate↗
PubMed1989

[The problem of selective vulnerability in neuropathology: the historical discussion between C. and O. Vogt and W. Spielmeyer as seen today (review)].

This review is focused upon the historical discussion on the topic of selective vulnerability. The extended controversy between C. and O. Vogt on the one side, and W. Spielmeyer on the other is reviewed. The major interest centers around the hippocampus where the phenomenon of selective vulnerability is most obvious. The theory of pathoclisis as proposed by the Vogts is reported which postulates physico-chemical peculiarities for different anatomical areas. Spielmeyer took an opposite position and stressed the vascular supply which was examined by Uchimura. The common issues of both theories are discussed, and the synthesis attempted by Scholz is explained. In the sense of an interim statement, present results from experimental research on cerebral ischemia and on selective vulnerability are discussed.

Brain Ischemia↗
PubMed1988

Polyamine metabolism in reversible cerebral ischemia: effect of alpha-difluoromethylornithine.

Severe forebrain ischemia was produced in rats by occluding both carotid and vertebral arteries. Following 30 min ischemia brains were recirculated for 8 or 24 h. Twelve animals subjected to 8 or 24 h recirculation (n = 6, each group) were given alpha-difluoromethylornithine (DFMO; injected intraperitoneally) immediately before recirculation. At the end of the experiments brains were frozen and samples were taken from the cerebellum, cortex, caudatoputamen and hippocampus. Samples from the left hemisphere were used for measuring ornithine decarboxylase (ODC) activity, and those from the right hemisphere for determining putrescine profiles. During recirculation ODC activity increased markedly in all brain structures, the most pronounced change being in the caudatoputamen after 8 h recirculation. Putrescine increased drastically after 8 h and even more after 24 h recirculation. DFMO-treatment significantly reduced ODC activity after 8 h recirculation and following 24 h recirculation. Putrescine, however, was significantly reduced following 24 h but not after 8 h recirculation. The discrepancy between reduction in ODC activity and putrescine levels in DFMO-treated animals was most prominent in the hippocampus after 8 h recirculation: here DFMO reduced ODC activity to control values without affecting putrescine levels. The results suggest that the observed overshoot in putrescine formation following ischemia is only partly caused by activation of ODC.

Animals↗
PubMed1988

Distribution of ischemic neuronal damage in the dorsal hippocampus of rat.

Selective neuronal death was investigated in dorsal hippocampus of rats subjected to 30 min of four-vessel occlusion (4VO) and recirculation times of 3, 8, 24, 48, and 72 h. Anatomical orientation was achieved in different subsectors by use of histochemical techniques for the enzyme acetylcholinesterase (AChE) and for heavy metals (Timm-stain). A systematic study of subsectors was performed in different section levels from mid-dorsal levels to the septal pole of the hippocampus. In the hilus of the dentate gyrus, there was early neuronal injury accompanied by microvacuolation of the neuropil. Delayed neuronal death occurred in sector CA1 in parallel to CA2 damage. The use of the Timm-stain allowed the first direct documentation of involvement of CA2 in ischemic injury. The CA3 sector was largely spared from lesions at mid-dorsal levels. At the septal extreme, however, there were lesions of CA3 pyramidal cells, and also portions of the dentate gyrus granule cells were affected. These findings demonstrate that all areas of the hippocampus can be involved in ischemic injury, depending on their position along the temporoseptal axis of the hippocampal formation.

Acetylcholinesterase↗
PubMed1987

Recovery of integrative central nervous function after one hour global cerebro-circulatory arrest in normothermic cat.

Functional and metabolic recovery of a female cat is described which survived for 1 year following 1 hour global cerebro-circulatory arrest at normothermia. Ischemia was produced by intrathoracal occlusion of the innominate, the left subclavian and both mammary arteries. Following ischemia the animal was kept under intensive care for 46 h. EEG and evoked potentials began to recover after 3 h following ischemia, and spontaneous respiration returned promptly on the 2nd day when the animal was weaned from the respirator. The neurological deficit score declined from a maximum of 395 immediately after ischemia to 158 during the first week and to 40 within 4 weeks. At this time the animal was slightly ataxic but she was able to walk and to feed and clean herself. One year after ischemia EEG and evoked potentials were normal. Morphological studies and the autoradiographic evaluation of protein biosynthesis revealed an almost normal pattern in cortical structures but there was almost complete atrophy of dorsal hippocampus and striatum leading to enlargement of the ventricular system. These observations demonstrate that despite these lesions the central nervous system is able to recover integrative neurological function after cerebro-circulatory arrest in normothermia of as long as 1 h.

Animals↗
PubMed1987

Pial artery pressure after one hour of global ischemia.

Pial artery pressure was measured in anesthetized control cats and in animals subjected to 1 h of global ischemia and 6 h of recirculation. Cerebral blood flow (CBF) was measured with the intraarterial 133Xe technique before and after ischemia, and lumped segmental resistances upstream and downstream to the pial artery were calculated. In the control brain, upstream resistance was 1.30 +/- 0.28 and downstream resistance 0.94 +/- 0.1 mm Hg ml-1 100 g min. During the postischemic hypoperfusion period, both resistances significantly increased, indicating that hypoperfusion constitutes a dysregulation of both large extracerebral and small intracerebral vessels. Hypercapnia induced an increase of CBF in the control brain and was accompanied by a fall in downstream resistance, demonstrating intracortical vasodilation. By contrast, hypercapnia did not provoke changes in either CBF or segmental resistances in the hypoperfusion period. In conclusion, during the postischemic hypoperfusion period, both extra- and intracortical resistances are increased and vascular reactivity to CO2 is abolished.

Animals↗
PubMed1987

Polyamine changes in reversible cerebral ischemia.

Putrescine, spermidine, and spermine levels were measured in the cortex, caudoputamen, and hippocampus of rats during 30 min of severe forebrain ischemia (induced by occlusion of both carotid and vertebral arteries) and subsequent recirculation. During ischemia, polyamine levels did not change significantly. During postischemic recirculation, however, putrescine levels dramatically increased whereas those of spermine and spermidine did not change, with the exception of the severely damaged caudoputamen, where the concentration declined after 24 h. The increase of putrescine is explained by postischemic activation of ornithine decarboxylase and inhibition of S-adenosylmethionine decarboxylase. It is suggested that the accumulation of putrescine during postischemic recirculation may be responsible for the delayed neuronal death occurring after ischemia.

Animals↗
PubMed1987

Lactate and pH in the brain: association and dissociation in different pathophysiological states.

Brain tissue pH and lactate content were measured in rats under three different experimental conditions, namely: during complete global cerebral ischemia; after reversible near-complete cerebral ischemia; and in experimental brain tumors. At the end of the experiments brains were frozen with liquid nitrogen. A series of 20-microns thick coronal sections was prepared in a cryostat and then used for the regional determination of tissue pH (umbelliferone technique) and tissue lactate (bioluminescent technique). In addition, tissue samples were taken for the quantitative measurement of brain lactate (enzymatic fluorometric technique). The relationship between lactate content and tissue pH was different for each of the three experimental models studied: only after short-term global cerebral ischemia did an increase in the lactate content correlate with a decrease in tissue pH (r = 0.94; p less than 0.001). A highly significant increase in the lactate content (p less than 0.001) was accompanied by physiological pH values (6.96 +/- 0.08 in comparison to 6.97 +/- 0.04 in controls) during recirculation after transient cerebral ischemia and in brain tumors even by an alkaline pH shift. In view of these observations the term "lactacidosis" should not be used without measuring both the lactate content and the pH. The observed dissociation between pH and lactate is due to the fact that both parameters are regulated independently. During anaerobiosis the main source of proton production is ATP hydrolysis rather than glycolysis. It is, therefore, suggested that the terms "acidosis" and "lactosis" should be used instead of "lactacidosis."

Animals↗
PubMed1986

Delayed recovery of CO2 reactivity after one hour's complete ischaemia of cat brain.

The cerebrovascular CO2 reactivity was examined after 6 h, 1, 2, and 3 days and 1 year following 1 h complete brain ischaemia in the cat. After 6 h recirculation, the CO2 reactivity was completely suppressed although major EEG activity had recovered. After 2 days, CO2 reactivity began to reappear, but even after 1 year restitution was not complete. The prolonged (though partly reversible) attenuation of CO2 responsiveness suggests that ischaemia is followed by a long-lasting state of haemodynamic imbalance, which may be responsible for the slow progress of post-ischaemic recovery processes.

Animals↗
PubMed1985

Mitochondrial calcium sequestration in cortical and hippocampal neurons after prolonged ischemia of the cat brain.

Adult normothermic cats were submitted to 1- h complete cerebrocirculatory arrest, followed by blood recirculation for 6-8 h. Two groups of animals could be distinguished: In one group electrocorticogram and somatically evoked primary cortical potentials steadily recovered after ischemia, and in another electrophysiologic recovery was absent. At the end of the recirculation period, calcium content was measured in tissue samples taken from cerebral cortex and hippocampus, and compared with mitochondrial calcium sequestration as assessed by electron-microscopic cytochemistry. Protein content of cortex and hippocampus was also determined for evaluation of tissue swelling. The two regions were selected because previous experiments had revealed that in animals with electrophysiologic recovery cerebral cortex remains intact although hippocampus is selectively injured, whereas in animals without electrophysiologic recovery both cerebral cortex and hippocampus are damaged. In animals with functional recovery, neither calcium content nor mitochondrial calcium sequestration were significantly increased in either cerebral cortex or hippocampal subfield CA1. Only in dentate gyrus a minor degree of mitochondrial calcium sequestration was present. Calculation of tissue swelling revealed no change in cerebral cortex, but a volume increase by 18% in hippocampus, indicating development of brain edema in this region. In animals without functional recovery tissue calcium significantly increased both in cortex and hippocampus (by 49% and 73% of control, respectively), and there was significant mitochondrial calcium accumulation in both regions. Calculated brain swelling in these animals amounted to 16% and 26% in cortex and hippocampus, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Use of acridine orange for histologic analysis of the central nervous system.

The application of the fluorescent dye acridine orange (AO) to the staining of histologic sections of the brain, and its use for automatic cyto- and histophotometric evaluation are described and compared with the results obtained using cresyl violet. The most suitable procedure for aldehyde-fixed brain tissue, embedded in paraffin and sectioned at 5 micron, proved to be treatment of the sections with an aqueous solution of AO (1:50,000) at pH 1.2 for 30 min, followed by rinsing in distilled water for 10 min. This procedure revealed the morphology in a highly acceptable manner, clearly differentiating various cell components; its characteristics included exact reproducibility and high contrast. The degree of fading was calculable, with a very gradual decrease in fluorescent intensity. The AO procedure appears to be compatible with most other staining procedures that do not rely on the same binding mechanisms. Thus, AO staining has two advantages over the classical cytoarchitectural staining methods: first, it is more suitable for automated morphometric analysis, and second, it can be used in conjunction with immunologic and other techniques.

Acridine Orange↗
PubMedDate not supplied

Polyamines in cerebral ischemia.

The present series of experiments was designed to study regional profiles of polyamines (putrescine, spermidine, and spermine) in reversible cerebral ischemia produced in rats and Mongolian gerbils. Polyamine profiles did not change during ischemia, but did following recirculation. The most prominent changes were a dramatic postischemic increase in putrescine and a marked decrease in spermine in severely damaged regions. Within a given brain structure, the postischemic putrescine levels correlated closely with the density of ischemic cell injury and the time period of cerebral ischemia. Furthermore, putrescine was already considerably increased in the CA1-subfield of the hippocampus of gerbils after 8 h recirculation, i.e., at a time when the cells are still intact. The results indicate that putrescine may be viewed as an excellent biochemical correlate of ischemic cell injury. The postischemic changes in putrescine levels are discussed in relation to the known activities of this compound.

Animals↗
PubMedDate not supplied

Relationship between metabolic recovery and the EEG prolonged ischemia of cat brain.

In normothermic cats, cerebral blood flow was arrested for 1 hour followed by blood recirculation for 5-6 hours. Functional recovery was evaluated by qualitative and quantitative EEG analysis, and metabolic recovery by measuring metabolite and electrolyte levels in tissue samples taken from the cerebral cortex. In 5 out of 12 animals EEG activity did not recover after ischemia (group I); in 3 animals, intermittent EEG activity (group II) and in 4 animals continuous EEG activity returned during the observation period (group III). In group I the energy state was severely disturbed and an increase of calcium was detected, in group II this disturbance was much less pronounced, and in group III changes in energy metabolism and ion concentration were absent with the only exception of lower ADP levels. During recovery, the total intensity of EEG correlated positively with ATP (p less than 0.01) and inversely with lactate (p less than 0.05), and the intensity of the delta band inversely with sodium content (p less than 0.05). The results obtained demonstrate that electrophysiological recovery after prolonged ischemia is closely correlated with the restoration of the energy state and of electrolyte homeostasis of the brain. The inverse relationship of EEG intensity with lactate and sodium are interpreted as evidence for the adverse effects of ongoing post-ischemic glycolysis, resulting in the activation of the H+/Na+ antiporter for the regulation of intracellular pH.

Animals↗