Biomedical subjects

J Frahm

Publications and source records attributed to J Frahm.

At least 19 recordsLinked to original sources

PubMed2006

ROS release and Hsp70 expression after exposure to 1,800 MHz radiofrequency electromagnetic fields in primary human monocytes and lymphocytes.

The aim of this study is to investigate if 1,800 MHz radiofrequency electromagnetic fields (RF-EMF) can induce reactive oxygen species (ROS) release and/or changes in heat shock protein 70 (Hsp70) expression in human blood cells, using different exposure and co-exposure conditions. Human umbilical cord blood-derived monocytes and lymphocytes were used to examine ROS release after exposure to continuous wave or different GSM signals (GSM-DTX and GSM-Talk) at 2 W/kg for 30 or 45 min of continuous or intermittent (5 min ON/5 min OFF) exposure. The cells were exposed to incubator conditions, to sham, to RF-EMF, or to chemicals in parallel. Cell stimulation with the phorbol ester phorbol-12-myristate-13-acetate (PMA; 1 microM) was used as positive control for ROS release. To investigate the effects on Hsp70 expression, the human monocytes were exposed to the GSM-DTX signal at 2 W/kg for 45 min, or to heat treatment (42 degrees C) as positive control. ROS production and Hsp70 expression were determined by flow cytometric analysis. The data were compared to sham and/or to control values and the statistical analysis was performed by the Student's t-test (P<0.05). The PMA treatment induced a significant increase in ROS production in human monocytes and lymphocytes when the data were compared to sham or to incubator controls. After continuous or intermittent GSM-DTX signal exposure (2 W/kg), a significantly different ROS production was detected in human monocytes if the data were compared to sham. However, this significant difference appeared due to the lowered value of ROS release during sham exposure. In human lymphocytes, no differences could be detected if data were compared either to sham or to incubator control. The Hsp70 expression level after 0, 1, and 2 h post-exposure to GSM-DTX signal at 2 W/kg for 1 h did not show any differences compared to the incubator or to sham control.

Antigens, CD↗

PubMed2006

Association of Jacobsen syndrome and bipolar affective disorder in a patient with a de novo 11q terminal deletion.

We report on a young woman with Jacobsen syndrome (JBS) who was admitted to our psychiatric department because of a bipolar affective disorder (BPAD). Chromosome analysis was performed due to the fact that she had mental retardation, short stature, and subtle facial anomalies. A deletion of the distal long arm of chromosome 11 was found. A detailed mapping of the deletion breakpoint by quantitative real time PCR revealed a true terminal 11q deletion of approximately 8 Mb corresponding to the karyotype 46,XX,del(11)(q24.2). Polymorphic DNA marker analysis showed that the deletion is located on the paternal chromosome. Additionally, laboratory investigations revealed a low platelet count and magnetic resonance imaging of the brain showed white matter T2 hyperintensities in frontotemporal regions, which are unlikely to result from a demyelinating process as indicated by localized proton magnetic resonance spectroscopy. To our knowledge, this is the first report describing a BPAD in a case with JBS.

Abnormalities, Multiple↗

PubMed2005

Compatibility of glass-guided recording microelectrodes in the brain stem of squirrel monkeys with high-resolution 3D MRI.

Knowledge of the precise position of recording microelectrodes within the brain of a non-human primate is essential for a reliable exploration of very small anatomic structures. This work demonstrates the compatibility of a newly developed glass-guided microelectrode design and microfeed equipment with high-resolution 3D magnetic resonance imaging (MRI). T1- and T2-weighted images allow for the non-invasive visualization of chronically implanted microelectrodes within the brain stem of squirrel monkeys in vivo. Neural extracellular multi-unit recordings proved the functionality of the microelectrode before and after the use of 3D MRI suggesting the preservation of normal brain tissue at the tip of the electrode. Because histology confirmed the absence of lesions attributable to MRI, the approach offers an interactive monitoring during the course of neuroethological experiments. Consequently, MRI may become an in vivo alternative to common histological post mortem verifications of electrode tracks and hence may avoid the early sacrificing of primates after only a small number of experiments.

Action Potentials↗

PubMed2005

Quantitative proton MRS of Pelizaeus-Merzbacher disease: evidence of dys- and hypomyelination.

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.

Aspartic Acid↗

PubMed2004

In vivo diffusion tensor mapping of the brain of squirrel monkey, rat, and mouse using single-shot STEAM MRI.

The purpose was to assess the potential of half Fourier diffusion-weighted single-shot STEAM MRI for diffusion tensor mapping of animal brain in vivo. A STEAM sequence with image acquisition times of about 500 ms was implemented at 2.35 T using six gradient orientations and b values of 200, 700, and 1200 s mm(-2). The use of half Fourier phase-encoding increased the signal-to-noise ratio by 45% relative to full Fourier acquisitions. Moreover, STEAM-derived maps of the relative anisotropy and main diffusion direction were completely free of susceptibility-induced signal losses and geometric distortions. Within measuring times of 3 h, the achieved resolution varied from 600x700x1000 microm3 for squirrel monkeys to 140x280x720 microm3 for mice. While in monkeys the accessible white matter fiber connections were comparable to those reported for humans, detectable fiber structures in mice focused on the corpus callosum, anterior commissure, and hippocampal fimbria. In conclusion diffusion-weighted single-shot STEAM MRI allows for in vivo diffusion tensor mapping of the brain of squirrel monkeys, rats, and mice without motion artifacts and susceptibility distortions.

Animals↗

PubMed2004

Stroke-like pattern in DTI and MRS of childhood mitochondrial leukoencephalopathy.

In a 13-month-old boy with recurrent motor deterioration provoked by fever MRI and proton MRS detected a leukoencephalopathy with reduced cerebral metabolites and elevated lactate. At follow-up 6 and 16 months later these abnormalities improved gradually. Serial diffusion tensor imaging revealed a stroke-like pattern with an initial strong reduction of the apparent diffusion coefficient followed by elevated values 6 months later. The relative diffusion anisotropy remained reduced. Muscle biopsy confirmed a mitochondrial encephalomyopathy.

Anisotropy↗

PubMed2003

Diffusion tensor imaging for long-term follow-up of corticospinal tract degeneration in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a predominantly clinical and electromyographic diagnosis. Conventional MRI reveals atrophy of the motor system, particularly the pyramidal tract, in the advanced stages but does not provide a sensitive measure of disease progression. Three patients with different principal symptoms of ALS, i.e., with predominant involvement of the upper (UMN) or lower (UMN) motor neurons, or bulbar disease, respectively, underwent serial clinical examination including lung function tests, conventional MRI, and diffusion tensor imaging (DTI). MRI demonstrated changes in of the pyramidal tract without measurable variation on follow-up. The patient with UMN involvement showed remarkable progressive loss of diffusion anisotropy in the pyramidal tract. DTI might be useful, together with clinical follow-up, as an objective morphological marker in therapeutic trials.

Amyotrophic Lateral Sclerosis↗

PubMed2003

Proton MRS profile of cerebral metabolic abnormalities in Krabbe disease.

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.

Adult↗

PubMed2003

Megalencephalic leukoencephalopathy with subcortical cysts in an adult: quantitative proton MR spectroscopy and diffusion tensor MRI.

A 37-year-old macrocephalic woman was investigated for increasing gait disturbance due to longstanding spasticity and ataxia. MRI showed widespread bilateral increase in signal from cerebral white matter on T2-weighted images. Numerous subcortical cysts were visible in anterior-temporal and parietal regions. These clinical and neuroradiological features are those of megalencephalic leukoencephalopathy with subcortical cysts (MLC), a recently delineated white-matter disease with onset in childhood. Quantitative localised proton MR spectroscopy of white matter revealed marked reduction of N-acetylaspartate, creatine, and choline with normal values for myo-inositol, consistent with axonal loss and astrocytic proliferation. Diffusion tensor imaging showed an increased apparent diffusion coefficient and reduced anisotropy in affected white matter pointing to reduced cell density with an increased extracellular space. These findings are in line with histological changes alterations known to occur in MLC.

Adult↗

PubMed2003

Magnetization transfer MRI of mouse brain reveals areas of high neural density.

Extending applications of magnetization transfer contrast (MTC) in magnetic resonance imaging (MRI) of the human central nervous system, this work quantitatively describes MTC of the murine brain. As a novel finding, complementing T(1)- and T(2)-weighted MRI, MTC allows for the distinction of densely packed gray matter from normal gray and white matter. Examples include the Purkinje cell layer and the granular cell layer in the mouse cerebellum as well as the delineation of the CA3 subfield of the hippocampus relative to surrounding hippocampal gray matter and white matter tracts such as the hippocampal fimbria. Using a kainate lesion model, the CA3 hyperintensities in MTC and T(1)-weighted MRI are assigned to the densely packed somata of pyramidal cells.

Animals↗

PubMed2003

Thresholding in correlation analyses of magnetic resonance functional neuroimaging.

The definition of objective and effective thresholds in MRI of human brain function is a crucial step in the analysis of paradigm-related activations. This paper introduces a user-independent and robust procedure that calculates statistical parametric maps based on correlation coefficients. Thresholds are introduced as p values and defined with respect to the physiologic noise distribution of the individual maps. Experimental examples from the human visual and motor system rely on dynamic acquisitions of gradient-echo echo-planar images (2.0 T, TR = 2,000 ms, 96 x 128 matrix) with blood oxygenation level-dependent contrast. The results demonstrate the disadvantages of thresholding with fixed correlation coefficients. In contrast, taking the individual noise into account allows for a derivation of p values and a reliable identification of highly significant activation centers. An adequate delineation of the spatial extent of activation may be achieved by adding directly neighboring pixels provided their correlation coefficients comply with a second lower p value threshold.

Brain↗

PubMed2003

Quantitative proton magnetic resonance spectroscopy of children with adrenoleukodystrophy before and after hematopoietic stem cell transplantation.

About 35-40 % of boys with X-linked adrenoleukodystrophy (ALD) develop a rapidly progressive cerebral form which leads to severe neurologic disability and death within 3-5 years after onset of clinical symptoms. Because previous proton magnetic resonance spectroscopy (MRS) studies of ALD identified metabolite patterns characteristic of demyelination, gliosis, and neuroaxonal loss, this work tested the hypothesis that MRS--apart from indicating disease progression--provides criteria for the outcome after hematopoietic stem cell transplantation (HSCT) which has been promising at an early stage of the active disease. Follow-up quantitative proton MRS was performed in frontal and occipital white matter of ALD patients (n = 12) before and up to 5 years after HSCT. The observed metabolite alterations were retrospectively correlated with the clinical outcome representing either a stable condition (n = 5), a further deterioration (n = 5), or death (n = 2). While disease progression of patients before HSCT was mainly characterized by a further increase of elevated choline-containing compounds (Cho) as an indicator of active demyelination, a positive outcome after HSCT was correlated with high N-acetylaspartate (tNAA) levels in affected white matter before HSCT yielding positive and negative predictive values for tNAA of 80 %. Although to be confirmed in a larger cohort of patients, the present findings suggest the preservation of neuroaxonal integrity as a prerequisite for an arrested course. Conversely, the combination of increased Cho with markedly reduced tNAA before HSCT apparently reflects a degree of tissue degeneration which precludes a successful therapeutic intervention.

Adrenoleukodystrophy↗

PubMed2002

High-resolution 3D MRI of mouse brain reveals small cerebral structures in vivo.

This work demonstrates technical approaches to high-quality magnetic resonance imaging (MRI) of small structures of the mouse brain in vivo. It turns out that excellent soft-tissue contrast requires the reduction of partial volume effects by using 3D MRI at high (isotropic) resolution with linear voxel dimensions of about 100-150 microm. The long T(2)* relaxation times at relatively low magnetic fields (2.35 T) offer the benefit of a small receiver bandwidth (increased signal-to-noise) at a moderate echo time which together with the small voxel size avoids visual susceptibility artifacts. For measuring times of 1-1.5 h both T(1)-weighted (FLASH) and T(2)-weighted (Fast Spin-Echo) 3D MRI acquisitions exhibit detailed anatomical insights in accordance with histological sections from a mouse brain atlas. Preliminary applications address the identification of neuroanatomical variations in different mouse strains and the use of Mn(2+) as a T(1) contrast agent for neuroaxonal tracing of fiber tracts within the mouse visual pathway.

Animals↗

PubMed2002

Distortion-free diffusion tensor imaging of cranial nerves and of inferior temporal and orbitofrontal white matter.

The main impact of functional neuroimaging has been its ability to locate neuronal activity either directly (EEG, MEG) or through the hemodynamic response caused by neuronal activity (PET, fMRI). In the past decade functional neuroimaging has been extended to investigate how brain regions interact, using the concepts of functional and effective connectivity. These concepts are further strengthened by estimates of anatomical connectivity of the same subject. A tool to determine anatomical connectivity in vivo may be provided by diffusion tensor imaging (DTI) methods. These can be used to determine the orientation of fiber bundles in white matter on the basis of the diffusion characteristics of water. Commonly, DTI data are acquired using echo planar imaging which suffers from susceptibility artifacts in orbitofrontal and inferior temporal cortex. Here we demonstrate the use of an alternative pulse sequence, diffusion-weighted single-shot STEAM, for assessing fiber orientation in orbitofrontal cortex and the cranial nerves. The scope of DTI needs to be extended to these structures to investigate psychiatric disorders in which orbitofrontal pathology or temporo-frontal disconnection have been postulated.

Adult↗

PubMed2002

Synaptic plasticity and tianeptine: structural regulation.

Stress-induced structural and cellular alterations in the hippocampus can contribute to the pathophysiology of depression. The reversal of these alterations may be a mechanism by which antidepressants achieve their therapeutic effect. The aim of the present study was therefore to investigate the effect of tianeptine on stress-induced structural changes and alterations in cerebral metabolites. To this end, psychosocially stressed male tree shrews were treated with tianeptine. A combination of in vivo and postmortem methods was used to evaluate the antidepressant treatment on the preservation of neuronal plasticity. It was found that all stress-induced effects were prevented by the administration of tianeptine. It is concluded that these findings provide experimental evidence for recent theories that impairment of neuronal viability and neuroplasticity might be important causal factors in mood disorders, suggesting tianeptine as a potential stimulator of neural resilience.

Administration, Oral↗

PubMed2002

Substance P receptor antagonist and clomipramine prevent stress-induced alterations in cerebral metabolites, cytogenesis in the dentate gyrus and hippocampal volume.

The neuropeptide substance P and its receptor, the neurokinin 1 receptor (NK(1)R) have been proposed as possible targets for new antidepressant therapies. The present study investigated the effect of the NK(1)R antagonist L-760,735 and the tricyclic antidepressant clomipramine in the chronic psychosocial stress paradigm of adult male tree shrews. Animals were subjected to a 7-day period of psychosocial stress before the onset of daily oral administration of L-760,735 (10 mg kg(-1) day(-1)) or clomipramine (50 mg kg(-1) day(-1)). The psychosocial stress continued throughout the treatment period of 28 days. Brain metabolite concentrations were determined in vivo by proton magnetic resonance spectroscopy. Cell proliferation in the dentate gyrus and hippocampal volume were measured post mortem. Stress significantly decreased in vivo concentrations of N-acetyl-aspartate (-14%), creatine and phosphocreatine (-15%) and choline-containing compounds (-15%). The proliferation rate of the granule precursor cells in the dentate gyrus was reduced (-45%), and hippocampal volume was decreased (-14%). The stress-induced changes of brain metabolites, hippocampal volume and dentate cytogenesis rate were prevented by concomitant drug administration. Elevated myo-inositol concentrations after both treatments hint to an astrocytic enhancement. These results suggest that-despite a different pharmacological profile-the NK(1)R antagonist L-760,735, a member of a novel class of antidepressant drugs, has comparable neurobiological efficacy to tricyclic antidepressants such as clomipramine.

Animals↗

PubMed2001

Functional MRI of cortical activations induced by transcranial magnetic stimulation (TMS).

The effects of repetitive transcranial magnetic stimulation (rTMS) on human brain activity and associated hemodynamics were investigated by blood-oxygenation-level-dependent (BOLD) MRI using echo-planar imaging at 2.0 T. Apart from bilateral activation of the auditory cortex by the audible rTMS discharges (23 bursts, 1 s duration, 10 Hz, 10-20 s interstimulus intervals), BOLD responses were restricted to cortical representations of actual finger movements performed either voluntarily or evoked by suprathreshold rTMS of the motor cortex. Neither subthreshold rTMS of the motor cortex nor suprathreshold rTMS of the lateral premotor cortex induced a detectable BOLD response. These findings suggest that neuronal depolarization as induced by rTMS modulates the spiking output of a brain area but does not automatically alter cerebral blood flow and oxygenation. The observation of BOLD MRI activations probably reflects the afferent intracortical processing of real movements.

Adult↗

PubMed2001

Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine.

Stress-induced structural remodeling in the adult hippocampus, involving debranching and shortening of dendrites and suppression of neurogenesis, provides a cellular basis for understanding the impairment of neural plasticity in the human hippocampus in depressive illness. Accordingly, reversal of structural remodeling may be a desirable goal for antidepressant therapy. The present study investigated the effect of tianeptine, a modified tricyclic antidepressant, in the chronic psychosocial stress model of adult male tree shrews (Tupaia belangeri), a model with high validity for research on the pathophysiology of major depression. Animals were subjected to a 7-day period of psychosocial stress to elicit stress-induced endocrine and central nervous alterations before the onset of daily oral administration of tianeptine (50 mg/kg). The psychosocial stress continued throughout the treatment period of 28 days. Brain metabolite concentrations were determined in vivo by proton magnetic resonance spectroscopy, cell proliferation in the dentate gyrus was quantified by using BrdUrd immunohistochemistry, and hippocampal volume was measured post mortem. Chronic psychosocial stress significantly decreased in vivo concentrations of N-acetyl-aspartate (-13%), creatine and phosphocreatine (-15%), and choline-containing compounds (-13%). The proliferation rate of the granule precursor cells in the dentate gyrus was reduced (-33%). These stress effects were prevented by the simultaneous administration of tianeptine yielding normal values. In stressed animals treated with tianeptine, hippocampal volume increased above the small decrease produced by stress alone. These findings provide a cellular and neurochemical basis for evaluating antidepressant treatments with regard to possible reversal of structural changes in brain that have been reported in depressive disorders.

Animals↗