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Otto W Witte

Publications and source records attributed to Otto W Witte.

At least 37 records · Page 2Linked to original sources
PubMed2004

Delayed neuronal death and damage of GDNF family receptors in CA1 following focal cerebral ischemia.

Delayed neuronal death (DND) of pyramidal neurons in the CA1 and CA3 regions of the hippocampus has been extensively studied following global brain ischemia, whereas only little is known about DND in this highly vulnerable brain region after focal brain ischemia. In the present study, the distribution and time course of hippocampal neuronal apoptosis were studied following transient middle cerebral artery occlusion (MCAO) in rats 1, 3, 7, 14, and 30 days after the insult. In 60% of the animals, more than 90% of CA1 pyramidal neurons showed strong nick-end labeling (TUNEL) staining at day 3 with fragmentation and marginalization of the nuclei in approximately 40% of these cells. The number of TUNEL-positive cells decreased within the next days, but 30 days after MCAO, some apoptotic neurons were still present. Analysis of the expression of the glial cell line-derived neurotrophic factor (GDNF) and its receptors GFRalpha1, GFRalpha2, and GFRalpha3 using triple immunofluorescence and confocal laser scanning microscopy revealed that in all animals showing marked hippocampal DND, the neuronal staining for GFRalpha1, GFRalpha3, and GDNF decreased prior to the onset of TUNEL staining in CA1. After 7 days, some apoptotic neurons still expressed GFRalpha3, whereas only few showed GFRalpha1 immunoreactivity, indicating that GFRalpha1 may be beneficial for the survival of hippocampal neurons. The data suggest that reduced expression of GDNF and impairment of GFRalpha1/3 may contribute to hippocampal DND after focal brain ischemia.

Animals↗
PubMed2004

Shrinkage of somatosensory hand area in subjects with upper extremity dysmelia revealed by magnetoencephalography.

The effect of peripheral lesions on cerebral somatosensory representations is well studied for experimentally induced amputations and deafferentations acquired later in life. However, few studies have investigated the brain's capacity for plastic changes in congenital malformations. We studied somatosensory-evoked fields to electrical stimulation of the bordering fingers in 10 subjects with upper extremity dysmelia in comparison with 10 control subjects using a 122-channel whole-head magnetometer. The number of developed fingers varied between two and four in the affected subjects. We localized finger representations in the primary somatosensory cortex and calculated Euclidian distances to estimate the size of the somatosensory hand area. Euclidian distances were significantly smaller in dysmelic subjects (5.7 mm) than in control subjects (11.6 mm) and were related to the number of the developed fingers on the contralateral hand. In contrast, individual finger representations were not found to be reduced. We suggest that the shrinkage of the somatosensory hand area might be related to the congenital nature of the malformation, to the smaller anatomical hand size in the affected subjects, and/or to use-dependent effects due to impaired hand function.

Adult↗
PubMed2004

Organic bipolar disorder occurring together with spontaneous intracranial hypotension.

Spontaneous intracranial hypotension (SIH) is known to cause postural headache, often combined with auditory, and vestibular symptoms, nausea, vomiting, and diplopia. We report a 63-year-old male patient who for the first time developed a depressive episode followed by acute manic symptoms during the course of SIH, both relieved after treatment of the underlying organic disturbance.

Bipolar Disorder↗
PubMed2004

Recovery of glucocorticoid-related loss of synaptic density in the fetal sheep brain at 0.75 of gestation.

Antenatal glucocorticoids routinely used to accelerate fetal lung maturation in human pregnancy at risk of preterm delivery decrease synaptic density and complex electrocortical activity in the fetal sheep brain at 0.87 gestation. We examined whether the effects of betamethasone on synaptic density depend on maturation of hypothalamo-pituitary-adrenal (HPA) axis and whether these effects are reversible. Betamethasone infusion to fetal sheep comparable to the dose used clinically (3.3 microg kg(-1) h(-1) over 48 h) at 0.75 gestation and, thus, before the prepartum increase of cortisol, reduced synaptophysin immunoreactivity (SY-IR) in the frontal neocortex, caudate putamen and hippocampus (P < 0.05). Loss of SY-IR exceeded that shown previously at 0.87 gestation (P < 0.05). It was not accompanied by neuronal damage and was reversible within 24h. In conclusion, fetal betamethasone exposure induces a gestational age-dependent decrease of synaptic density that is transient and more severe in younger fetuses.

Animals↗
PubMed2004

Impaired synaptic plasticity in the surround of perinatally acquired [correction of aquired] dysplasia in rat cerebral cortex.

Freeze-lesion induced neocortical dysplasias in rats mimic numerous aspects of human polymicrogyria and are used as a model for the study of developmental migration disorders. Since memory tests have demonstrated learning deficits in rodents with neocortical malformations, we investigated the expression and properties of long-term potentiation (LTP) in neocortical slices from adult freeze-lesioned and control rats. Field potentials, recorded in layer II/III at a distance of 2-3 mm lateral to perinatally induced microgyri, were strongly enhanced following theta-burst stimulation in layer VI (amplitude: 174 +/- 4%) compared to controls (110 +/- 2%). In contrast, in layer IV of the freeze-lesioned cortex LTP could not reliably be induced. Histochemical analysis, performed to elucidate the cellular basis of the impaired plasticity, revealed diminished amounts of the GABAA-receptor subunit gamma2 in the paramicrogyral zone, likely representing a diminished GABA-ergic filter, which is thought to prevent LTP induced in layer VI under normal conditions. Cytochrome-oxidase staining after electrophysiological examination disclosed that LTP in layer IV of the freeze-lesioned cortex could only be elicited, when stimulation was applied within a preserved barrel cortex. Our study provides evidence that focal cryolesions during cortical development cause an impaired synaptic plasticity that may underlie learning disabilities.

Animals↗
PubMed2004

Localization of the Na+-D-glucose cotransporter SGLT1 in the blood-brain barrier.

Immunoreactivity of the Na+-D-glucose cotransporter SGLT1 was demonstrated in intracerebral capillaries of rat and pig. Immunostaining suggested that SGLT1 is located in the luminal membrane of the endothelial cells and in intracellular vesicles. Using in situ hybridization, SGLT1 mRNA was not detectable in intracerebral capillaries of non-treated or sham-operated Wistar rats. However, 1 day after a transient occlusion of the right middle cerebral artery, SGLT1 mRNA was detected in capillaries of both brain hemispheres. Expression of SGLT1 was also demonstrated in primary cultures of capillary endothelial cells from pig using polymerase chain reaction after reverse transcription and western blotting. The data suggest that SGLT1 participates in transport of D-glucose across the blood-brain barrier and is upregulated after brain ischemia and reperfusion.

Animals↗
PubMed2004

Perilesional pathological oscillatory activity in the magnetoencephalogram of patients with cortical brain lesions.

In the surrounding of focal ischemic brain lesions dysfunctional neuronal zones emerge often resulting in pathological oscillatory activity. Using whole-head magnetoencephalography we recorded brain activity during rest in 23 patients with ischemic cortical lesions to find out whether we can localise and characterise low-frequency oscillatory activity. We measured patients at different times after stroke and partly in a follow-up approach to determine the time course of slow-wave activity. Using the analysis tool Dynamic Imaging of Coherent Sources we computed tomographic maps of oscillatory power in the delta-band (0.5-3 Hz). Fifteen of 23 patients with cortical strokes showed delta-activity, which was localised in an area not more than 2 cm away from the lesion. We found this perilesional low-frequency activity in the acute as well as in the chronic stage of stroke. Follow-up measurements of individual patients revealed persistence of perilesional low-frequency activity for months and even years. No consistent relation between perilesional activity and clinical symptoms was observed. Our results indicate that perilesional delta activity is common after ischemic cortical stroke. However, the functional significance remains to be elucidated.

Action Potentials↗
PubMed2004

A combined treatment with 1alpha,25-dihydroxy-vitamin D3 and 17beta-estradiol reduces the expression of heat shock protein-32 (HSP-32) following cerebral cortical ischemia.

1alpha,25-(OH)(2)-vitamin D(3) (1,25-D(3)) and 17beta-estradiol are both known to act neuroprotectively in certain experimental in vitro and in vivo settings and it has been noted that both steroids lead to an upregulation of certain neurotrophic factors. Here, we studied the effects of 1alpha,25-(OH)(2)-vitamin D(3) or 17beta-estradiol or their combined application on heat shock protein-32 (HSP-32) distribution after focal cortical ischemia using the well established photothrombosis model. Heat shock protein-32 is a well-established marker of the cerebral oxidative stress response and contributes to neuroprotection by metabolising cytotoxic free heme to carbon monoxide, iron and biliverdin. Photothrombotically lesioned rats were injected i.p. 1h after injury with either 1 microg 1alpha,25-(OH)(2)-vitamin D(3)/kg or 7 microg 17beta-estradiol/kg or a combination of both steroids. Groups of non-lesioned steroid-treated rats and lesioned, solvent-treated rats served as controls. In contrast to non-lesioned rats, in lesioned animals a significant increase in heat shock protein-32 expression occurred which was slightly, but non-significantly altered in the groups treated either with 1alpha,25-(OH)(2)-vitamin D(3) or 17beta-estradiol alone when compared to the solvent-treated control group. Only the combined treatment with 1alpha,25-(OH)(2)-vitamin D(3) and 17beta-estradiol resulted in a significant reduction of glial heat shock protein-32 immunoreactivity within the lesion-remote cortical areas supplied by the affected middle cerebral artery (MCA), indicating that both steroids act synergistically in a protective manner.

Animals↗
PubMed2004

Event-related fMRI with painful electrical stimulation of the trigeminal nerve.

Several functional brain imaging studies of pain using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have shown that painful stimulation causes activation of different brain areas. The aim of the present study was to develop and implement painful stimulation of the trigeminal nerve, which can be applied with event-related paradigms by using MRI. Twelve healthy, right-handed volunteers were examined. Painful electrical stimulation of the first trigeminal branch was performed. In an event-related setting with a 1.5 T clinical scanner with EPI capability, the following fMRI parameters were used: 20 slices, 3 mm thickness, isotropic voxel, 306 measurements with 54 randomized events. Statistical postprocessing was performed with SPM99. Activation of the ipsi- and contralateral secondary somatosensory cortex (SII), and the contralateral insular cortex was observed as well as a contralateral thalamic activation (T=4.45, extension 15 voxels). Six of the 12 volunteers revealed also activation of the cingulate cortex. The investigation demonstrates that painful stimulation of the trigeminal nerve activates the contralateral insular cortex, SII, and thalamus, as well as the ipsilateral SII. In contrast to other studies, the cingulate cortex was only activated inconsistently.

Adult↗
PubMed2004

Gene expression profiling in the intact and injured brain following environmental enrichment.

An enriched environment promotes structural changes in both injured and intact brain and improves behavioral performance. In 2 different experimental approaches, the effects of enriched surroundings were analyzed utilizing DNA microarrays. First, gene expression patterns of the sensorimotor cortex and the hippocampus of noninjured adult rats with enriched housing were compared with analogous regions of rats kept in standard cages. Second, circumscribed infarcts affecting the forelimb area of the sensorimotor cortex were induced, and gene expression patterns of the non-necrotic ipsilesional as well as the contralesional homotopic cortex of rats (postlesionally enriched housing versus standard) were analyzed. In the intact brain, the hippocampus, which had 43 upregulations and 15 downregulations showed more changes than the sensorimotor cortex, which had 13 upregulations and 4 downregulations, indicating a greater responsiveness of the hippocampus to environmental stimuli. In the injured brain, enrichment led ipsilesionally to 28 downregulations and 14 upregulations, while in the contralesional cortex, upregulations prevailed with 46 upregulations and 13 downregulations. The larger number of genes responsive to enrichment in the contralesional cortex (59 gene regulations) as compared to the analogous area (i.e. sensorimotor cortex) of the intact brain (17 gene regulations) likely reflects increased susceptibility for plastic changes due to injury. With the exception of the perilesional cortex, similar functional groups of genes were differentially regulated in different brain regions/paradigms, suggesting basically similar molecular cascades being involved in reorganizing the brain following external stimuli. Many of the genes detected here correspond to molecular pathways known to be involved in neuroplasticity, whereas others provide new and hitherto unrecognized entry points.

Animals↗
PubMed2004

Delayed shrinkage of the brain after ischemic stroke: preliminary observations with voxel-guided morphometry.

BACKGROUND AND PURPOSE: The most important effect of cerebral ischemia is brain infarction. In this magnetic resonance imaging (MRI) study, the authors aimed at assessing postischemic brain atrophy. METHODS: Ten patients suffering from their first acute cerebral ischemia in the territory of the middle cerebral artery were studied retrospectively. Three-dimensional MRI volume scans were recorded in the acute and chronic stage after infarction and analyzed voxel by voxel intraindividually with the newly developed voxel-guided morphometry. RESULTS: Shrinkage of brain tissue was detected in all patients, not only in the perilesional cortical structures but also in contralateral homolog cortex areas and subcortically in the striatum and thalamus. This secondary shrinkage was not related to the size of the infarcts or to the clinical outcome of patients. CONCLUSIONS: Our study suggests that delayed brain atrophy after acute ischemic stroke involved areas anatomically connected with the ischemic brain lesion but nevertheless was accompanied by a simultaneous improvement of the neurological deficit.

Atrophy↗
PubMed2003

Functional organization of the brain with malformations of cortical development.

We examined the localization of cerebral functions in 28 patients with focal epilepsy and malformations of cortical development (MCDs). Polymicrogyria occurred in nine, hemimegalencephaly in four, heterotopia in eight, and focal cortical dysplasia (FCD) in nine cases. We used simple (sensomotor, visual) or complex (language, memory) functional magnetic resonance imaging (fMRI) paradigms. Two thirds of MCDs were activated by simple fMRI paradigms, whereas they less frequently showed activity during complex cognitive fMRI paradigms. During simple paradigms, all disturbances of cortical organization (polymicrogyria, schizencephaly, and mild-type FCD) showed activity, whereas other MCDs (disturbances of earlier steps of cortical development: hemimegalencephaly, Taylor-type FCD, and heterotopia) showed activity in only 44% (p < 0.01). The association between the pathophysiology and morphology of MCDs confirms the recently proposed classification system. Both focal neurological signs (p < 0.05) and focal electroencephalogram slowing (p < 0.05) independently correlated with MCD inactivity, confirming that fMRI showed neuronal functions of MCDs. Conclusively, fMRI visualizes the MCD functions and their relationship to the eloquent cortex, providing useful information before epilepsy surgery. Surgery of cortical organization disturbances should be cautiously performed because these malformations may participate to some degree in brain functions.

Adolescent↗
PubMed2003

Gender-specific differences of hypometabolism in mTLE: implication for cognitive impairments.

PURPOSE: To determine gender differences of hypometabolism and their implications for cognitive impairment in patients with medically refractory mesial temporal lobe epilepsy (mTLE). METHODS: Regional cerebral glucose metabolism (rCMRGlu) was studied in 42 patients (21 male, 21 female) with either left- or right-sided mTLE (22 left, 20 right) and in 12 gender- and age-matched healthy controls during resting wakefulness and in 12 sex- and age-matched healthy controls. Clinical characteristics were balanced across the patient subgroups. All patients were subjected to neuropsychological assessment: 41 patients had histologic changes of definite or probable hippocampal sclerosis. RESULTS: Data analysis based on pixel-by-pixel comparisons and on a laterality index of regions of interest (ROIs) showed significant depressions of the mean rCMRGlu extending beyond the mesiotemporal region and temporolateral cortex to extratemporal regions including the frontoorbital and insular cortex in mTLE patients. Extramesiotemporal hypometabolism prevailed in the male patients. Metabolic asymmetry in temporal and frontal regions was related to performance in the Trail-Making Test and WAIS-R subitems. CONCLUSIONS: Our data showed a gender-specific predominance of extramesiotemporal hypometabolism in male patients with mTLE related to abnormalities of temporal and frontal lobe functions.

Adult↗
PubMed2002

Acute effects of cigarette smoking on cerebral oxygenation and hemodynamics: a combined study with near-infrared spectroscopy and transcranial Doppler sonography.

Cigarette smoking has been shown to increase cerebral blood flow velocity (CBFV) and reduce vasomotor reactivity temporarily. The aim of our study was to clarify whether this results from dilation of resistance vessels alone with subsequent increase in regional cerebral blood flow (rCBF), or an additional constriction of basal cerebral arteries. In 24 healthy smokers (mean age+/-S.D., 32.7+/-10.5 years), cerebral oxygenation and hemodynamics were monitored by transcranial Doppler sonography and near-infrared spectroscopy before, during, and after smoking a cigarette (nicotine 0.9 mg). We simultaneously recorded CBFV of both middle cerebral arteries, mean arterial blood pressure, skin blood flow, end-tidal CO(2), changes in concentration of cerebral oxyhemoglobin, deoxyhemoglobin, and total hemoglobin (micromol/l), and a cerebral tissue oxygenation index. Smoking increased CBFV (p<0.01), oxyhemoglobin (p<0.01), and total hemoglobin (p<0.01). After smoking, the increase in CBFV and total hemoglobin persisted (p<0.01), while oxyhemoglobin returned to baseline. Deoxyhemoglobin and cerebral tissue oxygenation index did not change during the whole procedure. During, but not after smoking, CBFV increase was correlated to ipsilateral changes in oxyhemoglobin and total hemoglobin (p<0.05). The increase in oxyhemoglobin only during smoking and the lack of changes in deoxyhemoglobin and cerebral tissue oxygenation index indicate that smoking did not substantially increase rCBF. The smoking-induced elevation in CBFV might therefore be due to an additional constriction of the middle cerebral artery. The combined effects of smoking on basal cerebral arteries and arterioles might contribute to the increased stroke risk in smokers.

Adult↗
PubMed2002

Use-related gene expression patterns of rat motor cortex.

Current evidence indicates reorganization of motor cortex in association with motor behavior. To investigate the molecular basis for these changes rats were fitted with limb-restricting vests which forced the use of one forelimb for 10 days. Using cDNA macroarrays, expression profiles of the corresponding motor cortices connected to the overused and immobilized limbs were analyzed. In the overused motor cortex up-regulations were observed exclusively, including genes coding for voltage-gated ion channels, trafficking and targeting proteins, and intracellular kinase network members (10 genes). In the contralateral immobilized cortex changes were restricted to down-regulation, mainly involving genes pertaining to DNA-binding, translation, neuronal signaling and metabolic pathways (9 genes). At least some of these changes are likely to represent the molecular substrate of use-dependent plasticity.

Animals↗
PubMed2002

Gene expression profiling in perilesional and contralateral areas after ischemia in rat brain.

Structural and functional reorganization in the vicinity of damaged neocortex and other connected brain areas seems to be responsible for postlesional functional recovery. To better understand the molecular mechanisms underlying this type of plasticity, gene expression patterns were analyzed by using DNA macroarrays comprising 1176 genes. Circumscribed unilateral infarcts consistently affecting the forelimb area of the motor cortex were induced photochemically in adult rats. Ten days after lesioning, cortical gene expression fingerprints were evaluated from an area adjacent to the lesion as well as two contralateral areas of motor and somatosensory cortex. Discrete regions showed distinct expression patterns. Upregulation was observed of different members of transcription factors, immediate early genes, neuronal signaling as well as neuronal growth and structure-associated genes, ipsilaterally (six genes) and/or contralaterally (eight genes in the motor and seven in the somatosensory cortex). In contrast, downregulations were restricted to ipsilateral areas and included genes coding for ion channels, transport proteins, mediators of metabolic pathways, and intracellular transducers (14 genes). A subset of these regulations were further confirmed by real-time polymerase chain reaction (TaqMan assay). At least part of the detected regulations, in particular those of the contralateral hemisphere, are likely to underlie plasticity processes.

Animals↗
PubMed2002

Widespread and long-lasting alterations in GABA(A)-receptor subtypes after focal cortical infarcts in rats: mediation by NMDA-dependent processes.

Impairment of inhibitory neurotransmission has been reported to occur in widespread, structurally intact brain regions after focal ischemic stroke. These long-lasting alterations contribute to the functional deficit and influence long-term recovery. Inhibitory neurotransmission is primarily mediated by gamma-aminobutyric acid (GABA)A receptors assembled of five subunits that allow a variety of adaptive changes. In this study, the regional distribution of five major GABA(A)-receptor subunits (alpha1, alpha2, alpha3, alpha5, and gamma2) was analyzed immunohistochemically 1, 7, and 30 days after photochemically induced cortical infarcts. When compared with sham-operated controls, a general and regionally differential reduction in immunostaining was found within the cortex, hippocampus, and thalamus of both hemispheres for almost all subunits. Within ipsilateral and contralateral neocortical areas, a specific pattern of changes with a differential decrease of subunits alpha1, alpha2, alpha5, and gamma2 and a significant upregulation of subunit alpha3 was observed in the contralateral cortex homotopic to the infarct. This dysregulation was most prominent at day 7 and still present at day 30. Interestingly, a single application of the noncompetitive N-methyl-D-aspartate-receptor antagonist MK-801 during lesion induction completely blocked these bihemispheric alterations. Cortical spreading depressions induced by topical application of KCl do not change GABA(A)-receptor subunit expression. As alterations in subtype distribution crucially influence inhibitory function, ischemia-induced modifications in GABA(A)-receptor subtype expression may be of relevance for functional recovery after stroke.

Animals↗