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Biomedical subjects

I Klatzo

Publications and source records attributed to I Klatzo.

At least 19 recordsLinked to original sources
PubMed2003

Cécile & Oskar Vogt: the significance of their contributions in modern neuroscience.

A) By introducing and propagating the use of multidisciplinary approaches, Cécile and Okar Vogt played a decisive role in establishing brain research as a distinct branch of science, and thus laid the foundations for modern Neuroscience. B) The Vogts' and Brodmann's monumental work on brain cytoarchitectonics, supplemented with electrical stimulation of the exposed cerebral cortex, demonstrated correlations between evoked functional responses and the topography of brain regions endowed with distinct cytoarchitectonic structure (topistic units). This opened the field of functional brain mapping, a subject hotly pursued at the present time. C) One of the most important aspects of Pathoclisis is that the Vogts based their theory on molecular genetics. They envisaged that in any topistic unit the neurons had a different specific, molecular ("physico-chemical") composition, accounting for differences observed in the dynamics of neuronal development and involution. In sublethal injury, the induced genomic reactivity varies according to the selective vulnerability of various topistic units. Thus, in cerebral ischemia, the fluctuating genomic reactivity may play a significant role in designing therapeutic strategies, which would include enhancing regenerative expressions and suppressing harmful ones. D) The pathoclisis theory may be of assistance in analyzing the nature of various genetic disorders, which could be considered for the application of gene therapy.

Germany↗
PubMed1999

Cortical spreading depression increases protein synthesis and upregulates basic fibroblast growth factor.

Protective effects of cortical spreading depression (CSD) against ischemic damage have been demonstrated in cortex when elicited at either 24 h or 3 days prior to ischemia. The present study was carried out to investigate possible mechanisms of neuroprotection following CSD. In Sprague-Dawley rats, 5 M KCl, 5 M NaCl, or physiological saline was applied to the cortex for 1 h. Repetitive CSD waves were elicited only in the KCl group. Measurements of cerebral glucose utilization demonstrated a marked reduction in affected cortex and subcortical regions in both the NaCl and the KCl groups, whereas cortical and hippocampal protein synthesis was discretely increased only in the KCl group. Immunohistochemistry of GFAP demonstrated a rapid activation in reactive astrocytes at 3 days in the KCl group whereas only a discrete activation was observed in the NaCl group. Similar changes were observed for basic fibroblast growth factor. Our results suggest that CSD-induced ischemic tolerance is not due to a reduction in energy metabolism but rather is associated with an upregulation of trophic factors and glial cell activation which might provide a mechanism for a long-lasting neuroprotection.

Analysis of Variance↗
PubMed1997

Cortical spreading depression induces long-term alterations of BDNF levels in cortex and hippocampus distinct from lesion effects: implications for ischemic tolerance.

Cortical spreading depression (CSD) protects hippocampal and cortical neurons from an otherwise lethal ischemic insult delivered days later. The present study was undertaken to evaluate changes in the expression of BDNF following CSD, distinct from lesion effects and its possible involvement in delayed ischemic tolerance. CSD was elicited by KCl application and a cortical lesion was made by hyperosmolar NaCl application. BDNF mRNA was examined by in situ hybridization and Northern blot up to 7 days post-CSD. BDNF protein content was measured by ELISA. In the cortex, BDNF protein was mildly elevated despite minimal increases of mRNA in the NaCl lesion group. CSD specifically up-regulated BDNF mRNA at 4 h, followed by a delayed secondary increase at 2-3 days. BDNF protein exhibited smaller biphasic increases at 24 h and 3-7 days post-CSD which were significantly higher than the NaCl lesion group. In the hippocampus, BDNF protein levels showed a delayed decrease in both groups independent of mRNA changes, but CSD specifically delayed this decrease. Thus, CSD can alter BDNF levels independent of lesion effects. The increased BDNF following CSD in the cortex is consistent with the involvement of BDNF in cortical ischemic tolerance. BDNF could not, however, be directly related to ischemic tolerance in the hippocampus.

Animals↗
PubMed1995

Loss of parvalbumin immunoreactivity defines selectively vulnerable thalamic reticular nucleus neurons following cardiac arrest in the rat.

The thalamic reticular nucleus (NRT) is one of the most vulnerable structures to selective neuronal damage both in human cardiac arrest patients and in experimental rodent global cerebral ischemia models. The detailed distribution of neuronal injury within the NRT was examined following 10-min cardiac arrest in the rat with conventional Nissl staining, 45Ca autoradiography and immunocytochemistry of the calcium binding proteins parvalbumin (PV) and calretinin (CR). While Nissl staining was almost unable to show the exact boundary of the nucleus and of the lesion, immunocytochemistry of PV proved to be the most useful index of the exact location and extent of neuronal loss in the NRT after ischemia. Calcium autoradiography was a sensitive method for detecting the lesion, and showed a similar distribution to the loss of PV staining, but did not give optimal spatial resolution. Quantitative analysis of PV staining at 7 days of recirculation demonstrated cell loss restricted to the lateral aspect of the middle segment of the NRT, identical with the distribution of large fusiform neurons in the somatosensory component of the nucleus. CR-positive neurons in the NRT were completely spared, although not all surviving neurons contained CR. These studies provide the first detailed characterization of the distribution of vulnerable neurons within the NRT after experimental ischemia and suggest that immunocytochemistry of PV is a useful tool for quantitative analysis of the lesion for use in further experiments to elucidate the mechanisms of selective vulnerability of the NRT.

Animals↗
PubMed1995

Development of susceptibility to audiogenic seizures following cardiac arrest cerebral ischemia in rats.

Susceptibility to audiogenic seizures (AGS) was investigated in Sprague-Dawley rats subjected to cardiac arrest cerebral ischemia (CACI), produced by compression of the major cardiac vessels. The onset of AGS was regularly observed 1 day after CACI of > 5 min duration. The duration of postischemic susceptibility to AGS was directly related to the density of cerebral ischemia, with 50% of more severely ischemic animals still showing AGS susceptibility 8 weeks after CACI. Lesioning of the inferior colliculi (IC) abolished the onset of AGS; no such effect was observed after lesioning the medial geniculate (MG). Glutamic acid decarboxylase (GAD) immunochemistry revealed approximately 50% loss of GAD-positive neurons in the IC, which was similar in animals with various durations of AGS susceptibility. Otherwise, there was a conspicuous sprouting of gamma-aminobutyric acid (GABA)-ergic terminals in the ventral thalamic nuclei, which peaked approximately 1 month after the CACI. Evaluation of GABA-A inhibitory function in the hippocampus by the paired pulse stimulation revealed changes indicating loss of GABA-A inhibition coinciding with the onset of AGS, and its return in animals tested 2 months after CACI. Our observations suggest a potential role of GABA-ergic dysfunction in the postischemic development of AGS.

Acoustic Stimulation↗
PubMed1995

Protective effect of spreading depression against neuronal damage following cardiac arrest cerebral ischaemia.

Effect of spreading depression (SD) on survival of CA1 hippocampal neurons was studied in Sprague-Dawley rats subjected to cardiac arrest cerebral ischaemia (CACI). SD was induced either by the topical application of KCI to the cerebral cortex (CSD) or by KCI perfusion of the hippocampus via a microdialysis cannula (HSD). CACI was carried out by intrathoracic compression of major cardiac vessels at 1, 3 and 7 days after CSD induction and 3 days after HSD, following which neuronal loss in the CA1 sector of the hippocampus was determined morphometrically. Our study revealed the significant protective effect of SD on survival of the CA1 pyramidal neurons in rats which were subjected to CACI 3 days later. No significant indication of a protective effect was observed in animals with SD induced 1 or 7 days prior to CACI nor in rats in which KCI was substituted by NaCl of equivalent concentration which did not induce any SD waves. Microdialysis assay during HSD showed a significant elevation of extracellular glutamate. Our studies, demonstrating an induction of a transitory period of neuronal resistance to ischaemia by preceding spreading depression, open an opportunity for elucidation of endogeneous factors responsible for the development of such resistance.

Animals↗
PubMed1993

Cardiac arrest-induced complete cerebral ischaemia in the rat: dynamics of postischaemic in vivo calcium uptake and protein synthesis.

Dynamics of pathological changes following cardiac arrest induced cerebral ischaemia were related to the findings of double tracer autoradiography of 45Ca and 3H leucine uptake as respective indicators of ischaemic injury and metabolic disturbance. Abnormal calcium accumulation, determined by 45Ca uptake, was related to injured but still living neurons and to reactive glial elements. 45Ca autoradiography confirmed a high sensitivity to neuronal injury of the nucleus reticularis thalami (NRT), hippocampal CA1 pyramidal layer, inferior colliculus, ventral thalamic nucleus (VTN), caudate nucleus, and parietal cortex. 3H leucine incorporation revealed that an initially widespread inhibition of protein synthesis was followed by its considerable recovery. Observations concerning hippocampal CA1 sector and VTN suggested that a significant degree of protein synthesis, maintained at the late stage after postischaemic recovery, was related to survival and regeneration of neurons and not to the presence of glial elements.

Animals↗
PubMed1992

Evidence for increased calcium influx across the choroid plexus following brief ischemia of gerbil brain.

Following 5 min ischemia of gerbil brain, unidirectional transfer of calcium from plasma to cerebrospinal fluid was measured quantitatively with 45CaCl2 at 4 days postischemic recirculation. 45Ca influx across the choroid plexus increased significantly from 0.0101 +/- 0.001 min-1 measured in sham-operated animals (n = 15) to 0.0294 +/- 0.002 min-1 determined in ischemic animals (n = 21; P less than 0.05). Histological examination of choroid plexus was carried out in Cresyl violet-stained sections from gerbils subjected to 5 min ischemia followed by 4 days (n = 6) and 7 days (n = 7) postischemic recirculation. Increased calcium transfer to cerebrospinal fluid was associated with cell damage of choroid plexus observed at 4 days postischemia. Endothelial choroid plexus injury was still detectable at 7 days after the ischemic insult suggesting a long-lasting pathomorphological process. Postischemic alterations in choroid plexus functions apparently expose brain tissue to much higher calcium influx into cerebrospinal fluid which, in turn, may contribute to calcium-related cell damage of the central nervous system.

Animals↗
PubMed1992

Global cerebral ischemia associated with cardiac arrest in the rat: I. Dynamics of early neuronal changes.

Light microscopic neuronal changes were studied in rats subjected to 10 min of global ischemia produced by compression of the major cardiac vessels. Observations of cresyl violet-stained sections revealed early changes involving predominantly GABAergic neurons in various locations. In rats killed 15 min after recirculation, the changes were characterized by the appearance of a clear peripheral zone with condensation of the remaining neuronal cytoplasm. After 1 h, these zones appeared to be compartmentalized into individual pearl-like vacuoles, especially prominent in the nucleus reticularis thalami. After 3 h, the cytoplasmic vacuoles disappeared and the neuronal changes, particularly in the cerebral cortex, striatum, hippocampus, and pars reticulata of the substantia nigra, consisted mainly of hyperchromasia or loss of Nissl substance. After 2 days, the cerebral cortex and thalamus contained occasional neurons with conspicuously large nucleoli. After 7 days, the hippocampus revealed an approximately 50% loss of CA1 pyramidal neurons, associated with intense microglial reactivity in the stratum radiatum, whereas the neuronal destruction was more complete in the nucleus reticularis thalami. Our observations suggest a possibility that early changes in GABAergic neurons may provide a period of neuronal disinhibition and thus contribute to an excitatory ischemic damage in regions connected by GABAergic circuitry.

Animals↗
PubMed1992

Reduced latency of the visual evoked cortical response following cryogenic injury to the cerebral cortex--a neuroexcitatory phenomenon.

Changes in the latency of visual cortical evoked responses (VER) were studied in rats subjected to cryogenic injury of the cerebral cortex. Four hours after cold injury the animals revealed a significant reduction of VER latency, which lasted approximately one week, with maximal reduction in latency occurring after 3 days. A potential role of excitotoxic amino acids in this phenomenon was tested by direct application of glutamate to the exposed cerebral cortex of the control rat and by administration of MK-801, antagonist of the NMDA receptor, in rats subjected previously to cryogenic injury and displaying a significant reduction in the VER latency. The direct application of glutamate to the cortex resulted in a decrease of the VER latency similar in magnitude to that observed after cold injury and this effect could repeatedly be demonstrated after washing out the initial application of the glutamate. The administration of MK-801 in animals subjected previously to cryogenic injury produced, within 5 minutes, reversion of reduced VER latencies. The maximal prolongation of latency occurred 30 min after MK-801 administration and reached in some cases latency values greater than in controls. Reduced latencies, corresponding to those observed originally, reappeared within 2 to 4 hours. Our studies suggest that the described reductions in the VER latencies are related to cortical areas of hyperexcitation due to excessive release of neuroexcitatory transmitters.

Animals↗
PubMed1992

Decreased visual evoked cortical response latency associated with cerebral ischaemia in the gerbil.

The observation of Xu et al. concerning reduction in latency of the visual evoked responses (VER) following cortical cryogenic injury, prompted us to ascertain whether similar VER changes could be demonstrable after ischaemic brain injury, especially, since both conditions have in common involvement of neuroexcitatory mechanisms. In our study, the Mongolian gerbils, which were subjected to 10 min bilateral carotid occlusion ischaemia, revealed decreased latency of the VER, with the peak of latency reduction between 4 and 7 h. An almost immediate decrease in VER latency was observed when glutamate was directly applied to the pial surface of the brain. These observations indicate that the reduction of VER latency may be related to neuroexcitation induced by release of excitatory amino acids, the latter constituting a widespread phenomenon, concomitant with brain injuries of various aetiologies.

Animals↗
PubMed1992

Oskar and Cécile Vogt, Lenin's brain and the bumble-bees of the Black Forest.

Oskar Vogt (1870-1955) was a prominent German neurologist and neuroanatomist with a strong interest in the pathogenesis of brain diseases. Together with his wife Cécile (1875-1962), he published landmark papers on the cyto- and myelo-architecture of the brain and the functional anatomy of the basal ganglia. He developed the concept of pathoclisis, i.e., the selective vulnerability of specific neuronal populations in the CNS. In the 1920's, Vogt created a multi-disciplinary brain research institute, the Kaiser-Wilhelm-Institut für Hirnforschung in Berlin-Buch. After Lenin's death in 1924, Oskar Vogt was called to Moscow where he formed a new brain research institute, with the main purpose to investigate the revolutionary's brain. After being dismissed from office by the Nazi government in 1937, the Vogts continued their work in a privately funded institute in Neustadt, the Black Forest.

Academies and Institutes↗
PubMed1990

Repetitive ischaemia of cat brain: pathophysiological observations.

The cumulative effect of repetitive ischaemia on brain injury was studied in halothane-anaesthetized cats submitted to three episodes of global cerebro-circulatory arrest. Ischaemia of 5.0, 7.5 and 10.0 min duration was produced at hourly intervals by intrathoracic clamping of the innominate and subclavian arteries, and the resulting pathophysiological changes were evaluated by recordings on the electroencephalogram (EEG), blood flow and specific gravity. During each episode of ischaemia EEG flattened within 15 s. After ischaemia the latency of EEG recovery increased with the duration and with the number of repetitions of each ischaemic episode, indicating cumulation of electrophysiological impairment. The flow studies revealed a minor degree of hyperaemia after each ischaemic episode, followed by severe hypoperfusion in the caudate nucleus but not in the cerebral cortex. Brain oedema - as assessed by specific gravity measurements - developed in the hippocampus after three episodes of 5 min ischaemia, and in all grey matter structures investigated after three episodes of 10 min ischaemia. To evaluate the resistance of the ischaemically injured brain to respiratory hypoxia, total oxygen was repeatedly reduced to 5% for 5 min. During these episodes EEG activity progressively declined as a function of the length and the repetition of ischaemia. Parallel n.m.r. spectroscopic measurements in the same model have demonstrated that disturbances of brain energy state during the hypoxic episodes are minor even after three episodes of 10 min ischaemia. EEG suppression, in consequence, is an electrical shut-down phenomenon for the maintenance of cerebral energy state under critical conditions of oxygen delivery.

Animals↗
PubMed1990

Putative neuroexcitation in cerebral ischemia and brain injury.

Involvement of neuroexcitatory mechanisms in cerebral ischemia and brain injury was explored in experimental models of repetitive forebrain ischemia by temporary occlusion of carotid arteries in gerbils and cryogenic injury to the cerebral cortex in rats and gerbils. Our observations in these models revealed a pattern of injury that involved some anatomic structures outside the areas of direct ischemic or traumatic insult. Such foci of injury revealed conspicuously abnormal uptake of 45Ca associated with slight or moderate neuronal alteration, whereas severely injured areas showed no 45Ca uptake. Electron microscopic observations revealed a characteristic presence of calcium in swollen dendrites, closely resembling pictures obtained in neuroexcitatory conditions such as epileptic seizures. Abnormal uptake of 45Ca was associated with apparent blood-brain barrier changes characterized by intracytoplasmic uptake of extravasated albumin into the neurons. Protein synthesis assayed by in vivo [3H]leucine incorporation was reduced in regions showing calcium accumulation. Our observations suggest that neuroexcitation may play an important role in development of secondary and chronic changes after ischemic or traumatic brain insults.

Animals↗
PubMed1990

[Changes in RCBF and edema after transient cerebral ischemia--ischemic threshold of postischemic hypoperfusion].

Brain damage after transient cerebral ischemia may be related to changes in postischemic cerebral blood flow and brain edema. In this study, the relationship between postischemic cerebral blood flow and edema was evaluated in the gerbil. Bilateral carotid occlusion (for 1, 1.5, 5, 15, or 30 min) was carried out in 110 female gerbils (50-70 g) under anesthesia with 2% halothane in 30% O2 and 70% NO2. Cerebral blood flow was measured by a [14C]-iodoantipyrine method modified slightly for use in small animals, and brain edema was evaluated by a specific gravity method. The threshold duration of ischemia which gives rise to subsequent hypoperfusion or edema was also established. In another 52 female gerbils under the same anesthesia, we investigated the effect of ischemia of variable duration on postischemic blood pressure and blood gas. Throughout all experiments, rectal temperature was maintained at 37-38 degrees C with a heating pad. Student's t test was used to calculate statistical significance. Neither blood pressure nor blood gas did vary significantly at any time following recirculation. Each brain region showed the same pattern of blood flow change, one almost independent of duration of occlusion. Namely, after the release of occlusion, transient recovery of blood flow was observed. But the flow then fell to 30-40% of the normal value at 1 h, after which it returned up to normal at 6 h. The severity of postischemic hypoperfusion was also independent of occlusion time. Interestingly, we did not observe postischemic hyperemia in any experimental groups except mild hyperemia in hippocampus after 5 and 15 min ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Cumulative effect of repeated ischemia on brain edema in the gerbil. Biochemical and physiological correlates of repeated ischemic insults.

Using a bilateral carotid artery occlusion model in the gerbil, we evaluated the cumulative effect of repeated ischemic insults on various physiological and biochemical parameters in brain. The most striking consequence of repeated occlusions is a profound, delayed increase in brain edema between 6- and 24-hr recirculation, after a series of three 5-min occlusions carried out at 1-hr intervals. This increment in brain water is accompanied by morphological evidence of compressed capillaries with increased filling of larger vessels, consistent with impaired microcirculation even though total blood flow and total vascular volume return toward control levels. The effect on edema is most severe when occlusions are repeated during the period of postischemic hypoperfusion, although the mechanisms responsible for this effect remain to be determined. Histograms of cerebral cortical oxygen tension show a shift toward progressively lower values during the recirculation interval after each occlusion, suggesting that secondary hypoxia accompanying hypoperfusion may worsen the impact of successive ischemic intervals. Although levels of PCr and ATP indicate adequate recovery of energy metabolism between occlusions, slight elevations of brain lactate persist, consistent with continued hypoxia. Under the conditions employed in these studies, repeated occlusions give rise to progressively more prolonged deficits in brain protein synthesis activity, which may thus provide a useful index of the severity of the accumulated ischemic insult. Continued studies using this well-defined model should provide further insight into the pathophysiology of ischemic brain edema.

Animals↗