Bernd Wilken
University of Göttingen
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Featured researches published by Bernd Wilken.
Pediatric Research | 1999
P. J. W. Pouwels; Knut Brockmann; Bernd Kruse; Bernd Wilken; Markus Wick; Folker Hanefeld; Jens Frahm
Regional changes of metabolite concentrations during human brain development were assessed by quantitative localized proton magnetic resonance spectroscopy in vivo. Apart from measurements in young healthy adults, the study was based on regional spectra from 97 children who were either healthy or suffered from mental retardation, movement disorders, epilepsies, neoplasm, or vascular malformation. Metabolite quantitation focused on cortical gray and white matter, cerebellum, thalamus, and basal ganglia in six age groups from infancy to adulthood. During infancy and childhood, the concentration of the neuroaxonally located N-acetylaspartate increased in gray matter, cerebellum, and thalamus, whereas a constant level was detected in white matter. These findings are in line with regional differences in the formation of synaptic connections during early development and suggest a role of N-acetylaspartate as a marker of functioning neuroaxonal tissue rather than of the mere presence of nerve cells. This view is further supported by high concentrations of taurine in gray matter and cerebellum during infancy, because taurine is also believed to be involved in the process of synapse formation. Remarkably, in basal ganglia both N-acetylaspartate and taurine remain constant at relatively high concentrations. Other metabolite changes during maturation include increases of N-acetylaspartylglutamate, especially in thalamus and white matter, and a decrease of glutamine in white matter. Despite regional differences and some small changes during the first year of life, the concentrations of creatine, phosphocreatine, choline-containing compounds, myo-inositol, and glutamate remain constant afterward. The creatine to phosphocreatine concentration ratio yields 2:1 throughout the human brain irrespective of region or age. The observed increase of the proton resonance line-width with age is most pronounced in basal ganglia and corresponds to the age-related and tissue-dependent increase of brain iron.
International Journal of Cancer | 2000
Jochen Herms; Iris Neidt; Bernhard Lüscher; Annete Sommer; Peter Schürmann; Thomas Schröder; Markus Bergmann; Bernd Wilken; Stephan Probst-Cousin; Pablo Hernáiz-Driever; Julianne Behnke; Folker Hanefeld; Torsten Pietsch; Hans A. Kretzschmar
To identify prognostic factors in medulloblastoma, a common malignant brain tumor of childhood, expression of the oncogene c‐myc was examined at the mRNA level by in situ hybridization. c‐myc mRNA expression was observed in 30 of 72 tumors (42%). The c‐myc gene copy number was determined by quantitative PCR from genomic DNA of paraffin‐embedded tumors. c‐myc gene amplification was present in 5 of 62 cases (8.3%). Therefore, c‐myc amplification was obviously not the cause of c‐myc mRNA expression in most samples. Kaplan‐Meier estimation revealed a significant correlation between c‐myc mRNA expression and survival (total mean follow‐up 4.6 ± 3.6 years, log‐rank p = 0.02). Multivariate logistic regression analysis including sex, age, histological type, degree of surgical resection and expression of synaptophysin, GFAP and c‐myc, was carried out on 54 patients who received both radiotherapy and chemotherapy. The analysis identified expression of c‐myc as an independent predictive factor of death from disease. Int. J. Cancer 89:395–402, 2000.
American Journal of Physiology | 1999
Peter Dechent; P. J. W. Pouwels; Bernd Wilken; Folker Hanefeld; Jens Frahm
The effect of oral creatine supplementation on brain metabolite concentrations was investigated in gray matter, white matter, cerebellum, and thalamus of healthy young volunteers by means of quantitative localized proton magnetic resonance spectroscopy in vivo (2.0 T, stimulated echo acquisition mode sequence; repetition time = 6,000 ms, echo time = 20 ms, middle interval = 10 ms, automated spectral evaluation). Oral consumption of 4 × 5 g creatine-monohydrate/day for 4 wk yielded a statistically significant increase (8.7% corresponding to 0.6 mM, P < 0.001) of the mean concentration of total creatine (tCr) when averaged across brain regions and subjects ( n = 6). The data revealed considerable intersubject variability (3.5-13.3%), with the smallest increases observed for the two male volunteers with the largest body weights. A regional analysis resulted in significant increases of tCr in gray matter (4.7%), white matter (11.5%), and cerebellum (5.4%) and was most pronounced in thalamus (14.6% corresponding to 1.0 mM). Other findings were significant decreases of N-acetyl-containing compounds in cerebellum and thalamus as well as of choline-containing compounds in thalamus. All cerebral metabolic alterations caused by oral Cr were reversible, as evidenced by control measurements at least 3 mo after the diet. This work demonstrates that excess consumption of Cr yields regionally dependent increases of the tCr concentration in human brain over periods of several weeks.
Neurology | 2003
Knut Brockmann; Peter Dechent; Bernd Wilken; O. Rusch; Jens Frahm; Folker Hanefeld
Background: Krabbe disease (globoid cell leukodystrophy [GLD]) is an autosomal recessive lysosomal disorder affecting the central and peripheral nervous system. The authors performed MRS to characterize metabolic alterations and their regional variation in brain tissue in GLD in vivo. Methods: Abnormalities of cerebral metabolite concentrations were assessed in seven patients with biochemically proven GLD—four with infantile, two with juvenile, and one with adult subtype—using quantitative localized proton MRS of standardized brain regions. Results: In infantile GLD, pronounced elevation of both myo-inositol and choline-containing compounds in affected white matter reflected demyelination and glial proliferation. The accompanying decrease of N-acetylaspartate pointed to neuroaxonal loss. Gray matter showed similar, albeit much milder alterations. In juvenile GLD, MRS indicated astrocytosis with minor neuroaxonal damage in white matter. In a patient with adult GLD, results of MRS of affected white matter were close to normal. MRS data are in agreement with histopathologic features of GLD. Conclusion: Proton MRS provides a powerful tool for assessing metabolic disturbances and the extent of brain damage noninvasively in GLD.
Respiration Physiology | 1997
Diethelm W. Richter; Peter M. Lalley; Olivier Pierrefiche; Akira Haji; Anne M. Bischoff; Bernd Wilken; Folker Hanefeld
Medullary respiratory neurons are influenced by a variety of neuromodulators, but there is a lack of information about the specific intracellular signal pathways involved. In this report we describe the modulatory effects of the cyclic adenosine-triphosphate (cAMP)-dependent protein kinase and of protein kinase C pathways on voltage- and ligand-controlled ionic conductances and demonstrate their functional significance in regulating the excitability of medullary respiratory neurons of the vivo cat. Evidence is presented that PKA and PKC pathways are persistently activated. PKA regulates current flow through persistently activated and GABAB receptor-controlled potassium channels as well as GABAA receptor-controlled chloride channels. PKC also depresses persistent potassium currents but it potentiates excitatory and inhibitory synaptic currents. The clinical significance of these intracellular signal pathways is demonstrated in a case of a child suffering from apneustic breathing, who was successfully treated with a 5HT-1A receptor agonist.
Pediatric Research | 1998
Bernd Wilken; Jan-Marino Ramirez; I Probst; Diethelm W. Richter; Folker Hanefeld
The effect of creatine (Cr) on the response of the respiratory center to anoxia was analyzed at different postnatal stages in a brainstem slice preparation of mice. Spontaneous rhythmic activity was recorded from hypoglossal rootlets (XII) and from identified neurons within the preBötzinger complex using the whole cell patch clamp technique. The hypoxic response was evaluated in slices from animals (n = 46), which received normal nutrition (controls, n = 16), from litters of animals fed with Cr (2 g/kg/day; nutrition group, n = 8), or after incubating slices for 3 h in Cr (200 μM) (incubation group, n = 22). ATP was measured in slices from controls and Cr-incubated slices which underwent 30-min anoxia. In neonatal animals (P0-5), amplitudes of hypoglossal bursts increased initially during anoxia by 14% in controls and by 41% in Cr-supplemented animals when compared with preanoxic values. Hypoglossal burst duration increased by 3% in controls, but by 18% in the Cr-nutrition group. In brainstem slices, the initial increase of amplitudes changed from 14%(controls) to 59% (Cr incubation) and prolongation of bursts from 3%(controls) to 37% (Cr incubation) compared with preanoxic values. In juvenile controls (P6-13), burst amplitude and duration increased by 12 and 14% during early anoxia when referred to preanoxic values. In slices from Cr-pretreated animals, increases of 48% (amplitude) and 21% (burst duration) occurred. The ATP levels remained constant during a 30-min anoxic period in the Cr-pretreated group compared with a decrease of 44% in slices from controls. Our data suggest that Cr can ameliorate hypoxic energy failure. Further studies will examine the neuroprotective potential in humans.
Neurology | 2005
Folker Hanefeld; Knut Brockmann; P. J. W. Pouwels; Bernd Wilken; Jens Frahm; Peter Dechent
Background: Pelizaeus–Merzbacher disease (PMD) is a rare X-linked recessive neurologic disorder caused by a mutation in the proteolipid protein (PLP) gene on chromosome Xq22. The associated depletion of PLP and severe reduction of other major myelin proteins results in dysmyelination. MRI reveals loss of T1 contrast between gray and affected white matter and T2 hyperintensities of white matter due to elevated water content. Methods: In vivo proton magnetic resonance spectroscopy (MRS) was used to determine cerebral metabolite patterns in five patients with genetically proven PMD. Absolute metabolite concentrations were obtained in cortical gray matter, affected white matter, and basal ganglia and compared to age-matched control values. Results: In comparison to age-matched controls, MRS of affected white matter resembled the metabolite pattern of cortical gray matter, as indicated by increased concentrations of N-acetylaspartate and N-acetylaspartylglutamate (tNAA), glutamine (Gln), myo-inositol (Ins), and creatine and phosphocreatine. Most remarkably, the concentration of choline-containing compounds was reduced. Parietal gray matter and basal ganglia appeared normal but showed a tendency for elevated tNAA, Gln, and Ins. Conclusions: Magnetic resonance spectroscopy (MRS)–detected alterations are consistent with enhanced neuroaxonal density, astrogliosis, and reduction of oligodendroglia. These disturbances in cellular composition are in close agreement with the histopathologic features characteristic of dys- and hypomyelination. The proton MRS profile of Pelizaeus–Merzbacher disease (PMD) differs from the pattern commonly observed in demyelinating disorders and allows PMD to be distinguished from other leukodystrophies.
Pediatric Neurology | 2000
Bernd Wilken; Peter Dechent; Jochen Herms; Caroline Maxton; Evangelos Markakis; Folker Hanefeld; J. Frahm
The diagnostic value of single-voxel proton magnetic resonance spectroscopy (2 T, stimulated echo acquisition mode, TR = 6,000 ms, TE = 20 ms, 4-5 mL volumes-of-interest) was assessed for a differentiation of focal brain lesions of unknown etiology in 17 patients 1-14 years of age. Absolute metabolite concentrations were compared with age-matched control subjects and an individual control region. Most of the brain tumors were characterized by strongly reduced total N-acetylaspartyl compounds and marked increases of myo-inositol and choline-containing compounds, consistent with a lack of neuroaxonal tissue and a proliferation of glial cells. Lactate was elevated in only four patients. When using this pattern for a metabolic discrimination of brain tumors from other focal lesions, proton spectroscopy correctly identified 14 of 17 abnormalities, as confirmed by histologic examination after neurosurgical intervention. One false-positive tumor diagnosis was a severe reactive gliosis mimicking a typical tumor spectrum. Two inconclusive cases comprised an astrocytoma with moderately elevated myo-inositol but reduced choline-containing compounds and a patient with an abscess leading to a marked reduction of all metabolites but strong contributions from mobile lipids. In summary, quantitative proton spectroscopy has considerable clinical value for preoperative characterization of focal brain lesions.
Archives of Disease in Childhood-fetal and Neonatal Edition | 2000
Bernd Wilken; Jan-Marino Ramirez; I Probst; Diethelm W. Richter; Folker Hanefeld
BACKGROUND Sufficient ATP concentrations maintain physiological processes and protect tissue from hypoxic damage. With decreasing oxygen concentration, ATP synthesis relies increasingly on the presence of phosphocreatine. AIM The effect of exogenously applied creatine on phosphocreatine and ATP concentrations was studied under control and anoxic conditions. METHODS Pregnant mice were fed orally with creatine monohydrate (2 g/kg body weight/day). Brainstem slices from these mice pups were compared with those from pups of non-creatine supplemented pregnant mice. Measurements were performed under normoxic and anoxic conditions. In addition, brainstem slices from non-creatine treated mice pups were incubated for 3 hours in control artificial cerebrospinal fluid (CSF) (n = 10) or in artificial CSF containing 200 μM creatine (n = 10). ATP and phosphocreatine contents were determined enzymatically in single brainstem slices. RESULTS ATP concentrations were in the same range in all preparations. However, there was a significant increase of phosphocreatine in the brainstems from pups of creatine fed mice when compared with the brainstems of pups from non-creatine treated mice or in non-incubated brainstems of control animals. After 30 minutes anoxia, ATP as well as phosphocreatine concentrations remained significantly higher in creatine pretreated slices compared with controls. CONCLUSION The data indicate that exogenous application of creatine is effective in neuroprotection.
European Journal of Pediatrics | 2003
Matthias Baumann; Christoph Korenke; Almuth Weddige-Diedrichs; Ekkehard Wilichowski; Donald H. Hunneman; Bernd Wilken; Knut Brockmann; Thomas Klingebiel; Dietrich Niethammer; Jörn Kühl; Wolfram Ebell; Folker Hanefeld
Abstract. In an attempt to elucidate prognostic factors, the data on 12 boys who underwent haematopoietic stem cell transplantation (HSCT) for cerebral X-linked adrenoleukodystrophy were evaluated. Two further patients received HSCT but died from transplantation-related complications. The data included neurological examination, neuropsychological testing and magnetic resonance imaging (MRI). Follow-up after HSCT was up to 5.5 years. Six patients showed a moderate to severe clinical deterioration after HSCT including two who died within 6 months. In this group, a MRI severity score of 10 or higher before HSCT was associated with severe impairment and a score of more than 12 was followed by rapid deterioration and death after HSCT. The presence of neurological symptoms before HSCT also affected prognosis. Six patients showed no deterioration in neurological or neuropsychological assessment after HSCT. Conclusion: our data confirm that haematopoietic stem cell transplantation can stop the progress of demyelination when performed at a critical early stage of the disease. The prognosis in an individual patient for the clinical course after stem cell transplantation can in general be given based on the status before transplantation, although individual patients may show an unexpected course.