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G Hagemann

Publications and source records attributed to G Hagemann.

At least 37 records · Page 2Linked to original sources
PubMed2000

Intact functional inhibition in the surround of experimentally induced focal cortical dysplasias in rats.

Early postnatal injections of ibotenate into the rat neopallium induce cortical dysplasias mimicking human polymicrogyria which often goes along with seizure disorders. Under in vitro conditions these experimentally induced dysplasias cause widespread hyperexcitability. The underlying mechanisms are as yet not fully understood. Electrophysiologically there is clear evidence of widespread alterations of the excitatory system. Intracellular recordings also showed some changes of the inhibitory system but have concentrated on recordings from focal areas close to the microgyrus. We investigated the integrity of functional inhibition using a paired-pulse paradigm to map the whole ipsilateral hemisphere. In rat cortical slices double-pulses were applied in layer VI/white matter and field potentials recorded in layer II/III. The ratio of the field potential amplitude did not show significant alterations in the dysplasias or their surround as compared with control and sham-injected animals. This result was obtained with two different locations of the dysplasias, excluding a mere areal specific effect. Our results show that despite prominent hyperexcitability in the surround of ibotenate-induced cortical dysplasias the inhibitory network appears to be functionally intact.

Animals↗
PubMed1999

Electrophysiological transcortical diaschisis after middle cerebral artery occlusion (MCAO) in rats.

Remote changes in brain function following stroke are called diaschisis. These remote effects may contribute to the neurological deficit following brain infarction; in addition they may lead to post-stroke epilepsy and affect functional recovery. In the present study we addressed the question of whether an increase in excitability can be observed contralateral to middle cerebral artery (MCA) infarction. Permanent occlusion of the middle cerebral artery (MCAO) was induced experimentally in rats with an intraluminal silicon-coated filament. Seven days later, brain excitability was tested with extracellulare recording techniques in neocortical coronal brain slices using a paired-pulse stimulus protocol. In rats with MCAO, excitability was increased in the neocortex contralateral to the infarction compared with the control group. These alterations extended through wide parts of the contralateral neocortex. The study demonstrates that MCAO causes transcallosal electrophysiological diaschisis. Together with results obtained previously with photothrombotic cortical lesions, it can be concluded that these remote effects are not due to characteristics of the individual lesion model, but are common consequences of brain lesions.

Animals↗
PubMed1999

Effects of tetanus toxin on functional inhibition after injection in separate cortical areas in rat.

Tetanus Toxin is widely used as a model of chronic focal epilepsy and is assumed to act by blocking neurotransmitter release with high selectivity for inhibitory synapses. However, the exact mechanisms are not fully understood, since, e.g., GABA release is only temporarily decreased although epileptiform activity persists pointing towards a change in the interplay of excitation and inhibition. Furthermore there have been reports about different effects of tetanus toxin after injection in separate brain areas. Therefore, we investigated the functional inhibition after injecting tetanus toxin either in the motor or sensory cortex of adult rats by using a paired-pulse paradigm as a measure of excitatory and inhibitory drive. Tetanus toxin injection into the motor cortex (n=10) induced a marked, long-lasting reduction in inhibition which was highly significant in most parts of the injected cortical area. Injections into the sensory cortex, however, showed less marked changes in inhibition which were more widespread and significant only in 3 of 14 animals injected. These results give further evidence for a prominent effect of tetanus toxin on functional inhibition and strengthen the idea of a differential effect in separate cortical areas. They may be accounted for by the different cytoarchitecture of cortical areas with variable inhibitory and excitatory intracortical connections.

Analysis of Variance↗
PubMed1999

Fast, accurate, and reproducible automatic segmentation of the brain in T1-weighted volume MRI data.

A new fast automated algorithm has been developed to segment the brain from T1-weighted volume MR images. The algorithm uses automated thresholding and morphological operations. It is fully three-dimensional and therefore independent of scan orientation. The validity and the performance of the algorithm were evaluated by comparing the automatically calculated brain volume with semi-automated measurements in 10 subjects, by calculating the brain volume from repeated scans in another 10 subjects, and by visual inspection. The mean and standard deviation of the difference between semi-automated and automated measurements were 0.56% and 2.8% of the mean brain volume, respectively, which is within inter-observer variability of the semi-automated method. The mean and standard deviation of the difference between the total volumes calculated from repeated scans were 0.40% and 1.2% of the mean brain volume, respectively. Good results were also obtained from a scan of abnormal brains.

Adult↗
PubMed1999

Possible carcinogenic effects of X-rays in a transgenerational study with CBA mice.

A lifetime experiment using 4279 CBA/J mice was carried out to investigate whether the pre-conceptual exposure of sperm cells to X-ray radiation or urethane would result in an increased cancer risk in the untreated progeny, and/or increased susceptibility to cancer following exposure to a promoting agent. The study consisted of four main groups, namely a control group (saline), a urethane group (1 mg/g body wt) and two X-ray radiation groups (1 Gy, 2 Gy). At 1, 3 and 9 weeks after treatment, the males of these four parental groups were mated with untreated virgin females. The offspring of each parental group was divided into two subgroups: one received s.c. urethane (0.1 mg/g body wt once) as a promoter, the other saline, at the age of 6 weeks. All animals were evaluated for the occurrence of tumours. K-ras oncogene and p53 tumour suppressor gene mutations were investigated in frozen lung tumour samples. The female offspring of male parents exposed to X-rays 1 week before their mating showed a trend towards a higher tumour incidence of the haematopoietic system than the F1 controls. In addition, a higher percentage of bronchioloalveolar adenocarcinomas in male offspring born to irradiated paternals mated 1 week after X-ray treatment points to a plausible increased sensitivity of post-meiotic germ cell stages towards transgenerational carcinogenic effects. On the other hand, no increased tumour incidence and malignancy were observed in the offspring born to irradiated paternals mated 3 and 9 weeks after X-ray treatment. Paternal urethane treatment 1, 3 and 9 weeks prior to conception did not result in significantly altered incidence or malignancy of tumours of the lung, liver and haematopoietic tissue in the offspring. K-ras mutations increased during tumour progression from bronchioloalveolar hyperplasia to adenoma. Codon 61 K-ras mutations were more frequent in lung tumours of urethane-promoted progeny from irradiated parents than from control parents. P53 mutations were absent from these lung alterations.

Adenocarcinoma↗
PubMed1998

Long-term evolution of excitotoxic cortical dysgenesis induced in the developing rat brain.

Cortical dysplasias are frequently caused by excitotoxic brain damage due to hypoxia or ischemia during development. Ibotenate, a glutamatergic agonist, was injected in the neopallium of rat pups at day of birth. The resulting cytoarchitectonic pattern includes neuronal depopulation in deep cortical layers, sulcus formation, and molecular ectopias, mimicking human polymicrogyria and disorders of neuronal migration. These cortical dysplasias persist until adulthood, providing a rat model to investigate the long-term functional consequences of cortical malformations.

Abnormalities, Drug-Induced↗
PubMed1998

Epileptiform discharges to extracellular stimuli in rat neocortical slices after photothrombotic infarction.

Seizures are one of the most frequent complications after cerebral ischemia in patients. Up to now it is unknown which mechanisms are responsible for this. As shown previously photothrombotic infarction in rat neocortex leads to a sweeping suppression of GABAergic inhibition. In this study we investigated whether and to what extent epileptiform discharges can be observed in this ischemia model. In neocortical slices from lesioned animals we did not find spontaneous epileptic activity or paroxysmal depolarisation shifts. However, ipsi- and contralateral to a photothrombotic lesion the frequency of double and multiple discharges was markedly increased when compared to unlesioned controls. Surprisingly, neither the drug lubeluzole which was has been shown to prevent the GABAergic disinhibition observed after photothrombotic lesioning of rat neocortex, nor the prevention of spreading depressions by the NMDA-receptor antagonist MK-801 during lesion induction significantly affected the frequency of epileptiform discharges. This indicates that the epileptiform discharges are probably caused by functional alterations of glutamatergic receptors.

Animals↗
PubMed1998

Increased long-term potentiation in the surround of experimentally induced focal cortical infarction.

Functional recovery after stroke is partly due to cortical reorganization on a structural as well as a functional level. Recent investigations have shown that the excitability of brain areas surrounding cortical ischemic lesions is increased, probably due to a down-regulation of gamma-aminobutyric acid-receptor activity. There is some evidence that these changes might increase the susceptibility of the lesioned brain for adaptive changes and recovery. Here, we investigated the propensity for the induction of long-term potentiation (LTP) in the surround of experimentally induced focal cortical infarcts in rat somatosensory cortex in vitro. By using standard paradigms, LTP induction was found to be facilitated ipsilaterally in slices of lesioned animals 1 week after lesion induction. In homotopic contralateral areas, LTP was not different from control values. As LTP is commonly associated with plasticity and learning, the results provide further evidence for the lesion-induced amplification of network plasticity, as it is required for the reshaping of cortical circuits by timely training procedures.

Animals↗
PubMed1998

Structural alterations and changes in cytoskeletal proteins and proteoglycans after focal cortical ischemia.

In order to study structural alterations which occur after a defined unilateral cortical infarct, the hindlimb region of the rat cortex was photochemically lesioned. The infarcts caused edema restricted to the perilesional cortex which affected allocortical and isocortical areas differently. Postlesional changes in cytoskeletal marker proteins such as microtubule-associated protein 2, non-phosphorylated (SMI32) and phosphorylated (SMI35, SMI31 and 200,000 mol. wt) neurofilaments and 146,000 mol. wt glycoprotein Py as well as changes in proteoglycans visualized with Wisteria floribunda lectin binding (WFA) were studied at various time points and related to glial scar formation. The results obtained by the combination of these markers revealed six distinct regions in which transient, epitope-specific changes occurred: the core, demarcation zone, rim, perilesional cortex, ipsilateral thalamus and contralateral homotopic cortical area. Within the core immunoreactivity for microtubule-associated protein 2 and SMI32 decreased and the cellular components showed structural disintegration 4 h post lesion, but partial recovery of somatodendritic staining was seen after 24 h. Microtubule-associated protein 2 and SMI32 persisted up to days 7 and 5 respectively in the core, whereas the number of glial fibrillary acidic protein- and WFA-positive cells decreased between days 7 and 14. The demarcation zone showed a dramatic loss of immunoreactivity for all epitopes 4 h post lesion which was not followed by a phase of recovery. In the inner region of the demarcation zone there was an invasion and accumulation of non-neuronal WFA-positive cells which formed a tight capsule around the core. Neuronal immunoreactivities for microtubule-associated protein 2, SMI31 and Py as well as astrocytic glial fibrillary acidic protein increased strongly within an approximately 0.4-1.0 mm-wide rim region directly bordering the demarcation zone. Py immunoreactivity increased significantly in the perilesional cortex, whereas glial fibrillary acidic protein-positive astrocytes became transiently more numerous in the entire lesioned hemisphere including strongly enhanced immunoreactivity in the thalamus by days 5-7 post lesion. Glial fibrillary acidic protein immunoreactivity increased in the corpus callosum and the homotopic cortical area of the unlesioned hemisphere by days 5-7. In this homotopic area additional changes in SMI31 immunoreactivity occurred. Our results showed that a cortical infarct is not only a locally restricted lesion, but leads to a variety of cytoskeletal and other structural changes in widely-distributed functionally-related areas of the brain.

Animals↗
PubMed1998

Uncoupling of blood flow and metabolism in focal epilepsy.

PURPOSE: Interictal measurements of cerebral blood flow are less helpful in localizing epileptic foci than are measurements of brain metabolism. This may be related to an uncoupling of blood flow and metabolism. In this study, brain metabolism and blood flow were compared in an acute experimental model of focal interictal epilepsy. METHODS: Interictal epileptic foci were induced by an epicortical application of penicillin in rats. After 1 h, stereotyped interictal activity was initiated, lasting until the end of the experiment. Brain metabolism was determined with [14C]deoxyglucose, and cerebral blood flow with [14C]iodoan-tipyrine autoradiography. RESULTS: In control experiments, metabolism and blood flow were coupled. In animals with focal interictal epileptic activity, the metabolism was strongly increased in the focus and reduced in areas lateral to the focus. In contralateral brain areas, blood flow and metabolism varied in a parallel fashion. Ipsilateral to the focus, however, blood flow and metabolism were altered disproportionately. In the focus, the increase of blood flow was less marked than the increase of metabolism, and the area with increased blood flow was larger than the area with increased metabolism. Lateral to the focus, in the area with a hypometabolism, blood flow was not concomitantly reduced. CONCLUSIONS: The experiments show that blood flow and metabolism in focal epilepsy may be uncoupled in widespread regions. This is due neither to structural abnormalities nor to the duration or discharge pattern of epileptic activity. The results explain why interictal metabolic investigations have a higher predictive value in presurgical epilepsy evaluation than do interictal measurements of blood flow.

Animals↗
PubMed1998

Brain hypometabolism in a model of chronic focal epilepsy in rat neocortex.

PURPOSE: Metabolic mapping of the human brain has become a widely used method for identifying and localizing epileptic foci. A reduction of glucose consumption usually is found interictally in the area of the focus. By contrast, animal models of acute epilepsy show a hypermetabolism in the epileptic focus. Here we investigated how metabolism is altered in an animal model of chronic epilepsy caused by focal injection of tetanus toxin into rat neocortex. METHODS: A total of 27 male Wistar rats were anesthetized and injected into the motor or sensory cortex either with dissolved tetanus toxin or with the solvent only. Animals recovered for 7, 14, or 30 days and then were anesthetized again for quantitative 14C-deoxyglucose autoradiography. Data were analyzed with an imaging program, and regional cerebral glucose metabolism (rCMRGlc) was determined. RESULTS: Injection of tetanus toxin into the motor cortex caused a focal hypometabolism which was confined to the cytoarchitectonic boundaries of the injected area, whereas sensory cortex injection caused a more widespread hypometabolism in all sensory cortical and connected, areas. None of the animals displayed focal hypermetabolism and we observed no significant time-dependent alteration of brain metabolism. CONCLUSIONS: Tetanus toxin injection into the cortex of the rat induces chronic epileptic activity accompanied by a focal hypometabolism. The data suggest that the spread of the metabolic alterations depends on the connectivity of the injected cortical area.

Animals↗
PubMed1998

[Comparison of film-screen combinations in contrast-detail diagram and with interactive image analysis. 3: Trimodal histograms of gray scale distribution in bar groups of lead pattern images].

The following four screen film combinations were compared: a) a combination of anticrossover film and UV-light emitting screens, b) a combination of blue-light emitting screens and film and c) two conventional green fluorescing screen film combinations. Radiographs of a specially designed plexiglass phantom (0.2 x 0.2 x 0.12 m3) with bar patterns of lead and plaster and of air, respectively were obtained using the following parameters: 12 pulse generator, 0.6 mm focus size, 4.7 mm aluminum prefilter, a grid with 40 lines/cm (12:1) and a focus-detector distance of 1.15 m. Image analysis was performed using an Ibas system and a Zeiss Kontron computer. Display conditions were the following: display distance 0.12 m, a vario film objective 35/70 (Zeiss), a video camera tube with a PbO photocathode, 625 lines (Siemens Heimann), an Ibas image matrix of 512 x 512 pixels with a spatial resolution of ca. 7 cycles/mm, the projected matrix area was 5000 micron 2. Maxima in the histograms of a grouped bar pattern were estimated as mean values from the bar and gap regions ("mean value method"). They were used to calculate signal contrast, standard deviations of the means and scatter fraction. Comparing the histograms with respect to spatial resolution and kV setting a clear advantage of the UVR system becomes obvious. The quantitative analysis yielded a maximum spatial resolution of approx. 3 cycles/mm for the UVR system at 60 kV which decreased to half of this value at 117 kV caused by the increasing influence of scattered radiation. A ranking of screen-film systems with respect to image quality and dose requirement is presented. For its evaluation an interactive image analysis using the mean value method was found to be superior to signal/noise ratio measurements and visual analysis in respect to diagnostic relevance and saving of time.

Humans↗
PubMed1997

Coupling of cortical and thalamic metabolism in experimentally induced visual and somatosensory focal epilepsy.

Focal epileptic activity induces widespread metabolic disturbances beyond the area of the electroencephalographically detectable focus. In order to find out whether the metabolic coupling between the epileptic focus and other brain regions depends on the localization of the focus, two groups of rats with epileptic foci at different sites were investigated. In the first group acute epileptic activity was induced by application of penicillin to the secondary visual cortex (Oc2), and in the second group to the primary somatosensory cortex (Par1). Metabolism was analyzed using the [14C]deoxyglucose autoradiographic method. In both groups of animals, hypermetabolism in the area of the focus and in specific functionally coupled thalamic nuclei was observed. Focal epileptic activity in the secondary visual cortex induced significant hypometabolism in remote ipsilateral cortical areas. In rats with epileptic foci in the primary somatosensory cortex hypometabolism in extrafocal ipsilateral cortical areas was less prominent. These findings provide further support for the integral involvement of the thalamus in modulating metabolism in remote cortical brain regions during focal epileptic activity. The extent of metabolic alterations may depend on the site of the epileptic focus and the connectivity of the recruited thalamic nuclei.

Animals↗
PubMed1997

[Comparison of film-screen combination in a contrast detail diagram and with interactive image analysis. 1: Contrast detail diagram].

The following three film-screen combinations were compared: a) a combination of anticrossover film and UV-light emitting screens, b) a combination of blue-light emitting screens and film, and c) a conventional green fluorescing screen film combination. Radiographs of a specially designed plexiglass phantom (0.2 x 0.2 x 0.12 m3) were obtained that contained bar patterns of lead and plaster (calcium sulfate) to test high and intermediate contrast resolution and bar patterns of air to test low contrast resolution, respectively. An aluminum step wedge was integrated to evaluate dose-density curves of the radiographs. The dose values for the various step thicknesses were measured as percentage of the dose value in air for 60, 81, and 117 kV. Exposure conditions were the following: 12 pulse generator, 0.6 mm focus size, 4.7 mm aluminum prefilter, a grid with 40 lines/cm (12:1), and a focus-detector distance of 1.15 m. The thresholds of visible bars of the various pattern materials were assessed by seven radiologists, one technician, and the authors. The resulting contrast detail diagram could not prove any significant differences between the three tested screen film combinations. The pairwise comparison, however, found 8 of the 18 paired differences to be statistically significant between the conventional and the two new screen-film combinations. The authors concluded that subjective visual assessment of the threshold in a contrast detail study alone is of only limited value to grade image quality if no well-defined criteria are used (BIR report 20 [1989] 137-139). The statistical approach of paired differences of the estimated means appeared to be more appropriate.

Humans↗
PubMed1997

[Comparison of film-screen combinations with contrast detail diagram and interactive image analysis. 2: Linear assessment of grey scale ranges with interactive image analysis].

The following three screen-film combinations were compared: a) a combination of anticrossover film and UV-light emitting screens, b) a combination of blue-light emitting screens and film, and c) a conventional green fluorescing screen-film combination. Radiographs of a specially designed plexiglass phantom (0.2 x 0.2 x 0.12 m3) with bar patterns of lead and plaster and of air, respectively were obtained using the following parameters: 12 pulse generator, 0.6 mm focus size, 4.7 mm aluminum pre-filter, a grid with 40 lines/cm (12:1) and a focus-detector distance of 1.15 m. Image analysis was performed using an IBAS system and a Zeiss Kontron computer. Display conditions were the following: display distance 0.12 m, a vario film objective 35/70 (Zeiss), a video camera tube with a PbO photocathode, 625 lines (Siemens Heimann), an IBAS image matrix of 512 x 512 pixels with a resolution of 7 lines/mm, the projected matrix area was 5000 microns2. Grey scale ranges were measured on a line perpendicular to the grouped bar patterns. The difference between the maximum and minimum density value served as signal. The spatial resolution of the detector system was measured when the signal value was three times higher than the standard deviation of the means of multiple density measurements. The results showed considerable advantages of the two new screen-film combinations as compared to the conventional screen-film combination. The result was contradictory to the findings with pure visual assessment of thresholds (part I) that had found no differences. The authors concluded that (automatic) interactive image analysis algorithms serve as an objective measure and are specifically advantageous when small differences in image quality are to be evaluated.

Algorithms↗
PubMed1996

Neuronal hyperexcitability and reduction of GABAA-receptor expression in the surround of cerebral photothrombosis.

Changes of neuronal excitability and gamma-aminobutyric acid (GABAA)-receptor expression were studied in the surround of photothrombotic infarcts, which were produced in the sensorimotor cortex of the rat by using the rose bengal technique. In a first series of experiments, multiunit recordings were performed on anesthetized animals 2-3 mm lateral from the lesion. Mean discharge frequency was considerably higher in recordings from lesioned animals (> 100 Hz in the first postlesional week) compared with control animals (mean, 15 Hz). These alterations were already present after 1 day but were most pronounced 3 to 7 days after lesion induction. Thereafter the hyperexcitability declined again, although it remained visible up to 4 months. In a second series of experiments, the GABAA-receptor expression was studied autoradiographically. This revealed a reduction of GABAA receptors in widespread brain areas ipsilateral to the lesion. The reduction was most pronounced in the first days after lesion induction and declined with longer intervals. It is concluded that cortical infarction due to photothrombosis leads to a long-lasting and widespread reduction of GABAA-receptor expression in the surround of the lesion, which is associated with an increased neuronal excitability. Such alterations may be responsible for epileptic seizures that can be observed in some patients after stroke and may contribute to neurologic deficits after stroke.

Animals↗