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Biomedical subjects

G W Eschweiler

Publications and source records attributed to G W Eschweiler.

15 recordsLinked to original sources
PubMed2006

[Brain-derived neurotrophic factor: from nerve growth factor to modulator of brain plasticity in cognitive processes and psychiatric diseases].

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family and plays an important role in neuronal survival and plasticity in the CNS. The proform of BDNF (pro-BDNF) is secreted and cleaved extracellularly by the serine protease plasmin to mature BDNF, which potentiates synaptic plasticity and long-term potentiation. Recent findings in animal models suggest an involvement of BDNF and its genetic functional single nucleotide polymorphism in the pathogenesis of different psychiatric diseases including depression, mania, schizophrenia, eating disorders, dementia, and Huntington's disease. In the brain and serum, BDNF is modulated by different factors. It is downregulated by stress and upregulated by learning processes, several antidepressive treatments, physical activity, and dietary restriction. Measurement of BDNF serum concentrations may be of diagnostic value. Additionally, the influence of different strategies for BDNF allocation seems to be relevant for the treatment and prevention of the above psychiatric disorders.

Animals↗
PubMed2005

Stage-dependent BDNF serum concentrations in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by cognitive decline and loss of neurons in specific brain regions. Recent findings have suggested an involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of AD. BDNF is an endogenous protein involved in the maintenance of neuronal function, synaptic plasticity and structural integrity in the adult brain. To our knowledge, the present pilot study assessed for the first time BDNF serum and CSF concentrations in 30 patients with different stages of AD in comparison to 10 age-matched non-demendet controls. AD patients were divided in two groups according to their MMSE score: Group 1 (n = 15) in early stages with MMSE scores >or=21 (mean of 25.5) and Group 2 (n = 15) with more severe stages of dementia with MMSE scores <21 (mean of 13.3). As main results, we found in patients with early stages of probable AD significantly increased BDNF serum concentrations as compared to more severe stages of AD (p < 0.0001) and age-matched healthy controls (p = 0.028). BDNF serum values in all AD patients correlated significantly with MMSE scores (r = 0.486; p < 0.0001). Levels of BDNF were below the detection limit of the assay in unconcentrated CSF samples of AD patients and non-demendet controls.In summary, BDNF serum values are increased in early stages of Alzheimer's disease, which may reflect a compensatory repair mechanism in early neurodegeneration and could also contribute to increased degradation of beta-amyloid (Abeta). During the course of the disease, BDNF is decreasing, which correlates with the severity of dementia. The decrease of BDNF may constitute a lack of trophic support with an increase of Abeta accumulation and thus contribute to progressive degeneration of specific regions in the AD-affected brain. BDNF should be further evaluated as a candidate marker for clinical diagnosis and therapeutic monitoring in Alzheimer's disease.

Aged↗
PubMed2003

Indicators of quality of in-patient psychiatric treatment: the patients' view.

OBJECTIVES: The object of this study was to find out from psychiatric in-patients which aspects of care and treatment they considered important and how satisfied they were with these. DESIGN: One hundred and ninety-four in-patients were asked to rate the importance of, and their satisfaction with, 22 different aspects of in-patient care and treatment. The questionnaire, developed for the purpose of the study after a pilot phase including professional care givers and patients, contained 92 items and was returned by 52% of all discharged patients from the Psychiatric university hospital during a 3-month period. RESULTS: Patients made a clear distinction between aspects of treatment they considered important and aspects they were satisfied with. Ranked of highest importance were various therapeutic relationships, and respect for their rights and privileges. They were satisfied with their relationships with clinical staff but dissatisfied with medication. CONCLUSION: A well differentiated assessment of importance and satisfaction has implications for the evaluation of the quality of psychiatric care, for specific methods of treatment, and for the improvement of in-patient psychiatric care.

Health Services Research↗
PubMed2002

[Correlation of diffusion-weighted magnetic resonance imaging with neurological deficits in sporadic Creutzfeldt-Jakob Disease].

This case report describes the sporadic Creutzfeldt-Jakob disease (CJD) of a 53-year-old man who initially complained about vertigo and dizziness. Within 18 weeks, he developed impaired memory, hemineglect, and sensory impairment of the left half of the body. A CSF tap was positive for 14-3-3 protein and showed increased tau protein, neuron-specific enolase (NSE), and the astroglial protein S-100 B. The EEG showed right temporal sharp waves without periodicity. Diffusion-weighted MRI revealed hyperintensities in the right temporo-occipital cortex which corresponded well with hypometabolic areas in a PET scan and the neurological and neuropsychological deficits. The morphological FLAIR T2 MRI showed no pathological changes. Within 20 weeks, the patient developed severe dementia with decreased spatial orientation and myoclonia, became incontinent, and was confined to bed. He died within 22 weeks after the first presentation of symptoms.

Creutzfeldt-Jakob Syndrome↗
PubMed2002

Heart-rate variability (HRV) in the ECG trace of routine EEGs: fast monitoring for the anticholinergic effects of clozapine and olanzapine?

Drug monitoring in psychiatry usually serves psychoactive drug plasma concentration measurement. Anticholinergic properties offer a faster approach to monitoring pharmacodynamic intraindividual effects of the drug by measuring their effects on heart rate variability (HRV), which is sympathetically and parasympathetically controlled via cholinergic synapses. The plasma concentrations of the atypical antipsychotics clozapine and olanzapine correlated with parameters of HRV in 59 patients suffering from schizophrenia or schizoaffective disorder. HRV during 4 minutes at rest was extracted from the ECG trace of a routine digital EEG registration in addition to blood sampling for plasma concentration measurement (HPLC method). We calculated sympathetically and parasympathetically controlled heart frequency bands (low, medium and high frequency) and other HRV parameters, coefficient of variation (CV), and root mean square of successive differences (RMSSD). All HRV parameters were significantly more impaired in clozapine patients (n = 33, mean clozapine plasma concentration 331 +/- 294 ng/ml) than in olanzapine patients (n = 26, mean olanzapine plasma concentration 42 +/- 32 ng/ml) and demonstrated 1.7 - 4.8 times the cardiac anticholinergic properties of clozapine in vivo. 14 out of 14 patients with a CV beyond 3.2 % had clozapine plasma concentrations below the proposed optimal therapeutic concentration of 350 ng/ml. All HRV parameters were inversely and significantly correlated with the clozapine plasma concentrations (such as lgCV: r = - 0.73, p < 0.001) and, to a lesser extent, with the olanzapine plasma concentrations (lgCV r = - 0.44, p < 0.05). These results underline the potential clinical value of HRV parameter extraction from routine ECGs in predicting plasma concentrations and objective individual neurocardiac effects of drugs with anticholinergic properties.

Adolescent↗
PubMed2001

[Which patients with major depression benefit from prefrontal repetitive magnetic stimulation].

Antidepressive benefit of prefrontal repetitive magnetic stimulation (RTMS) for one or two weeks varies between 6 % and 60 % (mean 37 %) improvement of the Hamilton depression scale vs. 12 % improvement following sham RTMS. This variance is probably caused by study specific stimulus parameters but also by genetic, psychopathological and neuropsychological characteristics of the patients as well as by the functional state of the cortex area below the stimulation coil. Data from 10 open and 7 sham controlled studies including two own studies comprising more than 300 patients with major depression have been published to date. In synopsis several positive predictors for antidepressive response of prefrontal RTMS become apparent: 1) younger age, 2) somatic signs of anxiety, 3) lack of cortical hyperactivity below the magnetic coil pulsed by 10 Hz stimuli, 4) cortical hypermetabolism below the 1 Hz pulsed coil. Negative predictors of response to prefrontal RTMS were: 1) Advanced age, 2) prefrontal atrophy, 3) cognitive impairment in neuropsychological tasks assigned to the prefrontal cortex, 4) psychotic symptoms, 5) cortical hyperactivity below 10 Hz pulsed coil 6) non-response to electroconvulsive therapy (ECT). While prefrontal RTMS will probably not replace ECT in severe major depression with psychotic symptoms it could be beneficial especially in younger anxious patients without cognitive impairment.

Clinical Trials as Topic↗
PubMed2000

Left prefrontal activation predicts therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) in major depression.

There is evidence that repetitive transcranial magnetic stimulation (rTMS) applied to the prefrontal cortex has antidepressive properties. In the present study we evaluated the clinical status and the hemodynamic responses during mental work in the prefrontal cortex before therapeutic rTMS. Twelve patients diagnosed with major depression (DSM-IV) were randomized in a sham-controlled cross-over treatment protocol of 4 weeks' duration consisting of two periods of 5 days with rTMS separated by 9 days of no stimulation. rTMS (10 Hz) was applied to the left dorsolateral prefrontal cortex. Hemodynamic changes in the prefrontal cortex during mental work were evaluated by multi-site near-infrared spectroscopy (NIRS). Scores on the Hamilton Depression Rating Scale (HAMD) decreased significantly by -5.4 points after 5 days of active stimulation, whereas it did not change (+1.6 points) after sham stimulation. Absence of a task-related increase of total hemoglobin concentrations at the stimulation site (P<0.005), but not at other locations, before the first active rTMS significantly predicted the clinical response to active rTMS. Clinical benefits of rTMS are predicted by low local hemodynamic responses and support the idea of activation-dependent targeting of rTMS location.

Brain Mapping↗
PubMed1994

[Neuronal protection in neurologic diseases?].

Several types of lesions of the mature central nervous system (CNS), such as craniocerebral trauma or spinal cord trauma, may initiate secondary cascades, which may cause damage to primarily uninjured neurons. The exact mechanisms which cause neuronal cell death are still unknown. It has been suggested that retrogradely transported target-derived neurotrophic factors which are necessary for neuronal survival might be lacking after certain types of lesions. On the other hand, neurons might be damaged by calcium-overload resulting from excessive release of excitatory amino acids (EAAs) after trauma. The present review summarizes current concepts of post-traumatic neuronal cell damage with a focus on the putative neuroprotective role of calcium channel blockers and their interaction with glutamate mediated cytotoxicity, neurotrophic factors and free radicals.

Amino Acids↗
PubMed1993

Temporal integration in visual cortex of cats with surgically induced strabismus.

Single unit response latencies in striate cortex after visual stimulation with stationary flashed bars were measured and interocularly compared in anaesthetized cats with surgically induced strabismus, in order to elucidate the neural basis of strabismic amblyopia. Four unilateral esotropic and two exotropic cats were studied. The visual onset latencies of cortical neurons ranged from 30 to 170 ms after stimulation of the non-deviating eye at a contrast of 82%. Responses after visual stimulation of the deviating eye were consistently delayed by approximately 10 ms. The latency increase was independent of the direction and absolute angle of squint in the different animals. Peak latencies of cortical neurons ranged from 43 to 245 ms. Median peak latency was 85 ms for the non-deviating and 95 ms for the deviating eye. The rise time of cortical flash responses, as determined from onset-peak differences, ranged between 2 and 170 ms. Direct interocular comparison of response latencies in the remaining binocular neurons revealed an invariable advantage for the non-deviating eye. Supragranular neurons showed a greater interocular latency difference than neurons in layer IV. Visual latencies were contrast-dependent. However, the latency reduction with increasing contrast was less pronounced for the deviating eye. We discuss the possibility that central integration times, especially within cortex, are prolonged in strabismic cats, affecting temporal coincidence of signal processing in the visual cortex. The resulting disturbance of spatio-temporal integration, as caused by a scrambling of geniculo-striate and intracortical connections, may be the substrate of binocular suppression and strabismic amblyopia.

Animals↗
PubMed1993

Formation of functional synapses by regenerating adult rat retinal ganglion cell axons in midbrain target regions in vitro.

The ability of adult rat retinal ganglion cell (RGC) axons to reinnervate normal target regions was examined in vitro. In co-culture experiments, adult rat retinal explants were placed adjacent to fetal rat midbrain sections that contained the superior colliculus (SC) which is the main target for RGC axons. Adult rat RGCs regrew axons over more than 500 microns on a polylysine-laminin substrate to reach the co-cultured explants. By using neurofilament immunohistochemistry and the fluorescent dye DiI for anterograde and retrograde tracing, it was shown that (1) adult rat RGCs with a stereotyped morphology survived in explant cultures for more than 4 weeks in the presence of fetal midbrain explants, (2) regenerating RGC axons preferentially terminated within midbrain target regions, and (3) RGCs formed functional synapses. In addition, the maturation of the SC region in midbrain explants was examined histologically and ultrastructurally to demonstrate appropriate target development.

Acetylcholinesterase↗
PubMed1993

Flunarizine enhances rat retinal ganglion cell survival after axotomy.

After axotomy most central nervous neurons including retinal ganglion cells (RGCs) die in a few weeks, although their somata are not injured. This neuronal death could be due to lack of retrogradely transported target derived neurotrophic factors or due to a calcium overload after excessive release of excitatory amino acids from dying cells. Flunarizine, as a potent blocker of voltage dependent Ca2+ channels and in higher concentration being an inhibitor of the Ca2+/calmodulin-dependent protein kinase II, is able to mimic the neurotrophic effect of NGF on dorsal root ganglion (DRG) neurons. To examine its neuroprotective value in the central nervous system (CNS), flunarizine (5 mg/kg body weight) was given daily to rats after unilateral axotomy of the optic nerve. The density of retrogradely labelled retinal ganglion cells (RGCs) was determined 14 days after axotomy. It could be demonstrated that flunarizine significantly enhanced RGC survival after axotomy in adult rats (P < 0.001; 1065 +/- 142 vs. 922 +/- 237 RGCs/mm2).

Animals↗
PubMed1992

Precrushed sciatic nerve grafts enhance the survival and axonal regrowth of retinal ganglion cells in adult rats.

We have examined the influence of normal and precrushed ("conditioned") sciatic nerve grafts on the survival and axonal growth of retinal ganglion cells (RGCs) in adult rats. Normal sciatic nerves (group A) or sciatic nerves which had been crushed 1 week before transplantation (group B, conditioned grafts) were used as grafts. The nerves were removed and sutured to the proximal stump of intraorbitally axotomized optic nerves. Neuronal survival and axon growth were determined by counting the numbers of surviving, DiI-prelabled RGCs, cresyl violet-stained RGCs and the numbers of axons which had grown into the grafts 3 and 6 months after transplantation. Counting of axons was performed by combined use of light and electron microscopy. We observed that the use of conditioned grafts (group B) significantly enhanced RGC survival and axonal regrowth as compared to normal grafts 3 months after transplantation. Six months after grafting, RGC survival (as determined in DiI-stained retinae) and axonal growth were not significantly different in both groups. These results suggest that the functional status of a peripheral nerve used for grafting in the CNS influences neuronal viability and axonal reelongation especially during the first 3 months after grafting. Very long-term RGC survival, however, may be determined by functional reconnection of regenerating RGC axons rather than by the graft itself.

Animals↗
PubMed1991

Regenerating adult rat retinal axons reconnect with target neurons in-vitro.

We have established an in-vitro coculture-system of adult rat retina with fetal midbrain explants to examine whether regenerating central nervous system axons are still able to recognize appropriate target neurons. Our results show that the retinal ganglion cell axons regenerate their axons and reinnervate the retino-recipient areas of cocultured fetal midbrain slices after one to seven weeks in-vitro. Functional connections as defined by electrophysiological criteria are detected only within these areas.

Animals↗