Biomedical subjects

Thomas Krause

Publications and source records attributed to Thomas Krause.

10 recordsLinked to original sources

PubMed2006

Modulation of NMDA receptor current in layer V pyramidal neurons of the rat prefrontal cortex by P2Y receptor activation.

Current responses to N-methyl-D-aspartate (NMDA) in layer V pyramidal neurons of the rat prefrontal cortex were potentiated by the P2 receptor agonists adenosine 5'-triphosphate (ATP) and uridine 5'-triphosphate (UTP). The failure of these nucleotides to induce inward current on fast local superfusion suggested the activation of P2Y rather than P2X receptors. The potentiation by ATP persisted in a Ca(2+)-free superfusion medium but was abolished by 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl) ester, cyclopiazonic acid, 7-nitroindazole, fluoroacetic acid, bafilomycin, and tetanus toxin, indicating that an astrocytic signaling molecule may participate. Because the metabotropic glutamate receptor (mGluR) agonists (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) (group I/II) and (RS)-3,5-dihydroxyphenylglycine (group I) both imitated the effect of ATP and the group I mGluR antagonist 1-aminoindan-1,5-dicarboxylic acid or a combination of selective mGluR(1) (7-(hydroxyimino)-cyclopropa[b]chromen-1a-carboxylate) and mGluR(5) (2-methyl-6-(phenylethynyl)pyridine) antagonists abolished the facilitation by ATP, it was concluded that the signaling molecule may be glutamate. Pharmacological tools known to interfere with the transduction cascade of type I mGluRs (guanosine 5'-O-(3-thiodiphosphate), U-73122, xestospongin C, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, calmodulin kinase II [CAMKII] inhibitor peptide) depressed the actions of both ATP and ACPD. Characterization of the P2Y receptor by agonists (ATP and UTP), antagonists (suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid), and knockout mice (P2Y(2)(-/-)) suggested that the nucleotides act at the P2Y(4) subtype. In conclusion, we propose that exogenous and probably also endogenous ATP release vesicular glutamate from astrocytes by P2Y(4) receptor activation. This glutamate then stimulates type I mGluRs of layer V pyramidal neurons and via the G(q)/phospholipase C/inositol 1,4,5-trisphosphate/Ca(2+)/CAMKII transduction pathway facilitates NMDA receptor currents.

Adenosine Triphosphate↗

PubMed2005

Preserved responsiveness of secondary somatosensory cortex in patients with thalamic stroke.

Cortical representations may change when somatosensory input is altered. Here, we investigated the functional consequences of partial "central" deafferentation of the somatosensory cortex due to a lesion of the ventroposterior lateral nucleus (VPL) in patients at a chronic stage after solitary infarction of the thalamus. Event-related functional magnetic resonance imaging during electrical index finger stimulation of the affected and nonaffected side was performed in 6 patients exhibiting contralesional sensory deficits (mainly hypesthesia). Involvement of the VPL and additional nuclei was determined by high-resolution magnetic resonance imaging (MRI) and subsequent MRI-to-atlas coregistration. For the group, statistical parametric maps showed a reduced activation of contralateral primary somatosensory cortex (SI) in response to stimulation of the affected side. However, no significant difference in the activation of contralateral secondary somatosensory cortex (SII) compared with stimulation of the nonaffected side was detected. Correspondingly, the ratio of SII-to-SI activation for the ipsilesional hemisphere was markedly elevated as compared with the contralesional hemisphere. For preserved responsiveness of SII in thalamic stroke comparable with that of the contralesional hemisphere, possible explanations are a direct thalamocortical input to SII mediating parallel information processing, nonlinear response behavior of SII in serial processing, or reorganizational processes that evolved over time.

Aged↗

PubMed2005

Sub-area-specific Suppressive Interaction in the BOLD responses to simultaneous finger stimulation in human primary somatosensory cortex: evidence for increasing rostral-to-caudal convergence.

In the primary somatosensory cortex (SI) of non-human primates, receptive field properties have been shown to differ between its sub-areas with increasing convergence in areas 1 and 2 as compared with area 3b. In this study, we searched for a similar functional organization of human SI. We performed fMRI in healthy subjects during separate or simultaneous electrical stimulation of the second and third finger of the right hand. Activation patterns in response to stimulation of single fingers reflected the somatotopical arrangement within the hand area of SI. Somatotopy was more clear-cut in area 3b as compared with areas 1 and 2. The response to simultaneous stimulation was considerably smaller than the summed responses to separate stimulation of each finger alone, pointing to a suppressive interaction effect. A region-of-interest analysis in the representational areas of the second and third finger revealed sub-area-specific differential suppressive interaction with an increase along the rostral-caudal axis (areas 3b, 1 and 2: 26, 32.7 and 42.2%, respectively). These findings on differences in the topographic as well as functional organization between sub-areas of SI support the notion of increasing convergence and integration from area 3b to areas 1 and 2 in human subjects.

Adult↗

PubMed2005

Separating functional and structural damage in persistent vegetative state using combined voxel-based analysis of 3-D MRI and FDG-PET.

Functional and structural damage in postanoxic persistent vegetative state (PVS) was analysed using 18fluorodeoxyglucose PET (FDG-PET) coregistered to 3-D MRI in combination with morphometric 3-D MRI analysis (voxel-based morphometry, VBM). In five patients in late stages of non-traumatic PVS, combined analysis using statistical parametric mapping (SPM2) was performed to compare metabolic impairment and structural loss. FDG-PET showed widespread hypometabolism at p<0.001 (corrected) in the parietal, parietooccipital and frontotemporal cortices, cingulum, frontal medial and precentral gyrus, and within the bilateral thalamus. VBM revealed multilocal structural loss at p<0.001 (corrected) in the inferior parietal and superior/medial frontal cortices, insula and operculum, superior and medial temporal lobes, cingulum and fusiform gyrus, caudate, midbrain, dorsal pons, and the cerebellum, but to a lesser extent in the thalamus. The selective vulnerability of the brain in a sample of PVS patients could be mapped in vivo, indicating that a complex structural and functional lesion pattern of the cerebral networks seems to be associated with this condition.

Adult↗

PubMed2005

The value of frozen section analysis of the sentinel lymph node in clinically N0 squamous cell carcinoma of the oral cavity and oropharynx.

OBJECTIVE: To determine the feasibility and accuracy of fine-sectioned frozen-section analysis of the sentinel lymph node (SLN) in cN0 oral cavity and oropharynx squamous cell carcinoma. STUDY DESIGN: Thirty-one patients were included and underwent lymphoscintigraphy a day before surgery and marking of the SLN. Intraoperatively, the SLNs were identified using a gamma probe, excised, and analyzed using fine-sectioned frozen section. The remaining SLN tissue was fixed in formalin for further staining and immunohistochemical analysis. An elective neck dissection was performed in all patients and all excised lymph nodes were examined for metastatic disease. RESULTS: SLNs were identified preoperatively by lymphoscintigraphy as well as by gamma probe intraoperatively in all patients. A total of 82 sentinel lymph nodes were excised and analyzed by fine-sectioned frozen section. Micrometastases were found in 16 out of the 82 SLNs, upstaging 14 out of 31 patients (45%) from cN0 to pN+. Furthermore, a total of 1295 lymph nodes from the neck dissection specimens were analyzed, confirming only one more metastatic disease. Sensitivity and negative predictive value of SLN biopsy were 93% and 94% respectively for frozen section analysis. CONCLUSION: Our study shows that SLN biopsy in cN0 neck of patients with oral cavity and oropharyngeal carcinoma is both feasible and accurate. Provided that larger studies confirm our results, an elective neck dissection may become unnecessary if fine-sectioned frozen-section analysis of the SLN shows no nodal metastases in patients with cN0 oral cavity and oropharynx carcinoma.

Aged↗

PubMed2004

D1 but not D2 dopamine receptors or adrenoceptors mediate dopamine-induced potentiation of N-methyl-d-aspartate currents in the rat prefrontal cortex.

Dopamine-glutamate interactions in the prefrontal cortex (PFC) are associated with higher order cognitive functions, and are involved in the pathophysiology of schizophrenia and addiction. Recordings with intracellular sharp microelectrodes and patch-clamp pipettes were used to investigate these interactions in layer V pyramidal cells of brain slices obtained from the rat PFC. Dopamine (100 microM) potentiated N-methyl-d-aspartate (NMDA; 10mM)-evoked depolarizations, but did not change those elicited by alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid (AMPA; 1mM). Dopamine (100 microM) increased the amplitude of the NMDA (30 microM)-induced currents as well, and 1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol (SKF 38393; 1, 10 microM), a D(1) receptor agonist, concentration-dependently reproduced this effect. Furthermore, 7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzapine hydrochloride (SCH 23390; 10 microM), a D(1) receptor antagonist, reversed both the dopamine- and the SKF 38393-evoked potentiation. The D(2) receptor agonists lisuride and quinpirole (10 microM both), as well as noradrenaline (100 microM) failed to mimic the stimulatory effect of dopamine. Isoproterenol (1, 10 microM) concentration-dependently facilitated NMDA responses. However, neither this effect at 10 microM nor that of dopamine at 100 microM could be antagonized by propranolol (10 microM), a non-selective beta adrenoceptor blocker. The isoproterenol-induced facilitation of NMDA currents was abolished by SCH 23390 (10 microM). The results indicate that dopamine potentiates NMDA responses in layer V pyramidal cells of the PFC solely by activating D(1) receptors. D(2) receptors and alpha or beta adrenoceptors are not involved in the dopamine-NMDA interaction.

Animals↗

PubMed2004

Adenosine A2A receptor-induced inhibition of NMDA and GABAA receptor-mediated synaptic currents in a subpopulation of rat striatal neurons.

The function of adenosine A(2A) receptors, localized at the enkephalin-containing GABAergic medium spiny neurons of the striatum, has been discussed controversially. Here we show that, in the absence of external Mg(2+), the adenosine A(2A) receptor agonist CGS 21680 postsynaptically depressed the NMDA, but not the non-NMDA (AMPA/kainate) receptor-mediated fraction of the electrically evoked EPSCs in a subpopulation of striatal neurons. Current responses to locally applied NMDA but not AMPA were also inhibited by CGS 21680. However, in the presence of external Mg(2+), the inhibition by CGS 21680 of the GABA(A) receptor-mediated IPSCs led to a depression of the EPSC/IPSC complexes. The current response to the locally applied GABA(A) receptor agonist muscimol was unaltered by CGS 21680. Whereas, the frequency of spontaneous (s)IPSCs was inhibited by CGS 21680, their amplitude was not changed. Hence, it is suggested that under these conditions the release rather than the postsynaptic effect of GABA was affected by CGS 21680. In conclusion, under Mg(2+)-free conditions, CGS 21680 appeared to postsynaptically inhibit the NMDA receptor-mediated component of the EPSC, while in the presence of external Mg(2+) this effect turned into a presynaptic inhibition of the GABA(A) receptor-mediated IPSC.

Adenosine↗

PubMed2003

Activation of a residual cortical network during painful stimulation in long-term postanoxic vegetative state: a 15O-H2O PET study.

Survivors of prolonged cerebral anoxia often remain in the persistent vegetative state (PVS). In this study, long-term PVS patients were investigated by 15O-H(2)O PET to analyze their central processing of pain. The study was approved by the local Ethics Committee, the experiments were performed in accordance with the Helsinki Declaration of 2000. Seven patients remaining in PVS of anoxic origin for a mean of 1.6 years (range 0.25-4 years) were investigated. We performed functional PET of the brain using 15O-labelled water during electrical nociceptive stimulation. Additionally, a brain metabolism study using 18F-fluorodeoxyglucose (FDG) PET and multi-sequence MRI (including a 3-D data set) were acquired in all patients. PET data were analyzed by means of Statistical Parametric Mapping (SPM99) and coregistered to a study-specific brain template. MRI and FDG PET showed severe cortical impairment at the structural and the functional level, that is, general atrophy of various degrees and a widespread significant hypometabolism, respectively. Pain-induced activation (hyperperfusion) was found in the posterior insula/secondary somatosensory cortex (SII), postcentral gyrus/primary somatosensory cortex (SI), and the cingulate cortex contralateral to the stimulus and in the posterior insula ipsilateral to the stimulus (P<0.05, small-volume-corrected). No additional areas of the complex pain-processing matrix were significantly activated. In conclusion, the regional activity found at the cortical level indicates that a residual pain-related cerebral network remains active in long-term PVS patients.

Adult↗

PubMed2002

Cerebral regional hypometabolism caused by propofol-induced sedation in children with severe myoclonic epilepsy: a study using fluorodeoxyglucose positron emission tomography and statistical parametric mapping.

Cerebral positron emission tomography (PET) in children often requires sedation. This study evaluated sedation-associated effects on cerebral glucose metabolism in 30 children with severe myoclonic epilepsy as investigated by cerebral (18)F-fluorodeoxyglucose (FDG)-PET. Prior to the PET acquisition, 24 children underwent propofol sedation. Pixel-based t-statistics were calculated using statistical parametric mapping (SPM99) for comparisons of the patients' PET scans with both a healthy adult control group and an age-matched child intra-group control. In both analyses, statistically significant hypometabolic areas were found in the medial parieto-occipital cortex bilaterally, including the lingual gyrus, cuneus, posterior cingulate and middle occipital gyrus in all sedated children. All these localizations correlated in a covariate analysis with the injected dose of propofol (P<0.01, corrected). The bilateral parieto-occipital hypometabolism is likely to be a sedation-specific effect and should be taken into account when evaluating cerebral FDG-PET scans in sedated children.

Adolescent↗

PubMed2002

Event-related fMRI of the somatosensory system using electrical finger stimulation.

Cortical signal intensity changes due to brief (1 s) innocuous electrical stimuli applied to the second and fifth finger of the right hand were measured by means of fMRI at 1.5 T. The activation pattern in this event-related fMRI approach closely resembled that obtained in recent block-design studies. Activations were found in contralateral primary (SI) and bilaterally in secondary (SII) somato-sensory cortex as well as in posterior parietal cortex, insula, and supplementary motor area (SMA). In SI, the somatotopic organization of the hand area is demonstrated, more clearly to be seen in area 3b than in area 1 and 2. In conclusion, the feasibility to employ event-related somatosensory stimulation paradigms in fMRI studies is demonstrated.

Adult↗