PubMed Health⌕ Search

Biomedical subjects

F Block

Publications and source records attributed to F Block.

At least 37 records · Page 2Linked to original sources
PubMed2001

Evaluation of R6/2 HD transgenic mice for therapeutic studies in Huntington's disease: behavioral testing and impact of diabetes mellitus.

R6/2 transgenic mice express exon 1 of the human Huntington's disease (HD) gene with an increased CAG repeat length. They develop a progressive neurological phenotype, die within 12-14 weeks of age and were also found to develop diabetes mellitus. Since R6/2 mice are broadly used to screen for potential therapies in HD, the aim of this study was (a) to search for behavioral tests that are best applicable to monitor the behavioral abnormalities in therapy studies and (b) to investigate the extent to which diabetes influences the disease phenotype. We found that the rotarod test for motor coordination and the open field test for spontaneous explorative behavior were useful to monitor the progressive behavioral deterioration of R6/2 mice. An accelerating rotarod paradigm was superior over testing with a rotarod at various fixed speeds since it leads to similar results with less repetitive daily trials so that exhaustion cannot contribute substantially to their decline in performance. With the Morris water maze, however, it was only possible to monitor cognitive decline in visuo-spatial learning in the first weeks of disease since, at later stages, mice were not able to learn the task adequately. A latent diabetes mellitus was found in all transgenic mice demonstrated by a pathological glucose tolerance. Only 26% of the mice, however, were found to develop a manifest diabetes with increasing blood glucose levels on normal diet over the disease period. R6/2 mice with manifest and latent diabetes showed no significant differences in survival, weight loss, motor coordination, or spontaneous explorative behavior. These results suggest that diabetes mellitus is not a major contributing factor to the disease phenotype.

Animals↗
PubMed2001

Interleukin-6 expression in exo-focal neurons after striatal cerebral ischemia.

Although anatomical and biochemical properties of the rat entopeduncular nucleus (EPN) closely resemble those of the substantia nigra pars reticulata (SNr), the present study shows that, unlike in the SNr, focal cerebral ischemia does not cause trans-synaptic degeneration of EPN neurons, despite striatal infarction and a similar delayed glial activation in both nuclei. In this study, interleukin-6 (IL-6) expression was found within EPN neurons 3 and 7 days after striatal ischemia. Since it has been reported that neuroprotective properties seem to predominate IL-6 function and that distinct SNr regions which demonstrate low trans-synaptic neuronal degeneration show high IL-6 expression and vice versa, IL-6 expression within partially deafferentiated but surviving EPN neurons could represent an intrinsic neuroprotective mechanism.

Animals↗
PubMed2001

Time course of glial proliferation and glial apoptosis following excitotoxic CNS injury.

Activation of microglial cells and astrocytes after CNS injury results in changes in their morphology, immunophenotype and proliferative activity and has neurotrophic as well as neurotoxic consequences. However, little is known about the exact time course of glial activation as regards their proliferative activity and their fate. In this study, quantification of the densities of proliferating and non-proliferating microglial cells and astrocytes was carried out over 30 days by counting differentially labeled cells in the striatum and substantia nigra pars reticulata (SNr) after injection of quinolinic acid into the rat striatum. The TdT-mediated dUTP nick end labeling (TUNEL)-reaction was used to detect possible apoptotic mechanisms which limit the glial reaction. At 1 day post injection (p.i.) non-proliferating ameboid microglia/macrophages were seen in the striatum, but at 3 and 5 days p.i. many proliferating, ameboid microglia/macrophages and hypertrophic microglia were detected. At 10 days p.i., the time point with the highest density of hypertrophic microglia, TUNEL-positive microglial cells were observed indicating that apoptotic processes play a role in restricting this reaction. In contrast to this, at early time points, a reduction in the density and glial fibrillary acidic protein (GFAP)-immunoreactivity of astrocytes in the striatum was detected. At later time points, a dense astrogliosis with proliferating astrocytes developed in the dorsal and medial striatum. At 30 days p.i., in the entire striatum a dense astrogliosis was detected. The SNr showed a short period of microglial activation and proliferation and a long lasting astrogliosis without proliferation

Animals↗
PubMed2001

Rolipram reduces excitotoxic neuronal damage.

Proinflammatory cytokines are supposed to be involved in the pathophysiology of neuronal damage following excitotoxic lesions. We examined the effect of rolipram, a TNF-alpha-inhibitor, on excitotoxic neuronal damage. Quinolinic acid (240 nmol in 1 microl) was injected stereotactically into the striatum of male Wistar rats. Four groups of QA rats were treated i.p. with solvent, MK-801 (4 mg/kg) or rolipram (0.3 mg/kg) which was started either 6 or 24 h after QA injection and continued with daily applications for 14 days. QA injection induced neuronal damage which affected 93% of the striatal area. MK-801 reduced this damage to 12% of the striatal area. Treatment with rolipram when started at 6 h after QA injection resulted in neuronal damage amounting to 60%; the result after starting at 24 h was not different from solvent (91%). The present results demonstrate that rolipram reduces neuronal damage induced by intrastriatal QA application.

Animals↗
PubMed2001

Inflammation contributes to the postponed ischemic neuronal damage following treatment with a glutamate antagonist in rats.

The present study examined whether anti-inflammatory drugs can ameliorate the postponed neuronal damage which has been observed following treatment of ischemic animals with 2,3-dihydro-6-nitro-7-sulfamoyl-benz (F) quinoxaline (NBQX). Global cerebral ischemia was induced in male Wistar rats by four-vessel occlusion for 20 min. The animals were treated either with NBQX, rolipram, doxycycline or a combination of NBQX and rolipram or doxycycline. Four weeks after ischemia neuronal damage in the hippocampus was assessed. Treatment with NBQX or doxycycline did not affect ischemic neuronal damage whereas rolipram alone or combination of NBQX with either rolipram or doxycycline reduced neuronal damage. The present study shows that combining NBQX with an anti-inflammatory drug leads to long-lasting protection. These results suggest that inflammation contributes to the postponed neuronal damage following treatment with NBQX.

Animals↗
PubMed2001

Focal ischemia induces transient expression of IL-6 in the substantia nigra pars reticulata.

We examined the expression of IL-6 in the substantia nigra pars reticulata (SNr) at various time points after transient (3 h) middle cerebral artery occlusion (MCAO) in rats. The animals were killed at 1, 3, 7 or 14 days following operation. Coronal brain sections were processed for immunohistochemistry with antibodies against GFAP, OX-42 and IL-6 and for Nissl staining. Microglial activation was detected 3 and 7 days after ischemia. Reactive astrocytes have been found 7 and 14 days after ischemia. IL-6 expression was detected 3 and 7 days after ischemia. IL-6-positive cells beared the typical morphology of neurons. Distribution of IL-6-positive cells within the SNr was not homogenous. The lateral area of the SNr bears the highest number of IL-6-positive neurons while the central core bears the lowest. Quantification of intact neurons in the SNr 14 days after reperfusion shows that the highest amount of cell loss was found in the central core of the SNr and less neuronal cell loss was observed in the lateral area of the SNr. Thus, the SNr area with the highest IL-6 expression 3 and 7 days after ischemia bears the highest number of intact neurons 14 days after ischemia. This finding could be a clue for the neuroprotective role of IL-6 in the remote region SNr after focal cerebral ischemia.

Animals↗
PubMed2001

[Gabapentin therapy for pain].

Gabapentin, which has been approved for add-on therapy of focal seizures, is increasingly used for treatment of neuropathic pain. Its analgesic effect is supposed to be due to reduction of glutamatergic transmission, improvement of GABAergic transmission and to binding to voltage-dependent calcium channels. Experimental studies demonstrated an ameliorating effect of gabapentin on neuropathic pain. Placebo-controlled studies revealed an efficacy of gabapentin against pain in diabetic neuropathy and postherpetic neuralgia and in prophylaxis of migraine. Case reports show an analgesic effect of gabapentin in trigeminus neuralgia and in reflex sympathetic dystrophy. The main adverse events are dizziness, ataxia and somnolence. Controlled studies, which compare the efficacy of gabapentin with that of the respective reference drug, are needed to evaluate its importance in treatment of pain.

Acetates↗
PubMed2001

[Glutamate antagonists in neurology].

Glutamate is the major excitatory neurotransmitter of the central nervous system. Besides its importance in many physiological processes, increased glutamate release and subsequent excessive stimulation of the various glutamate receptors are thought to play critical roles in the pathophysiological mechanisms underlying many neurologic diseases. Experimental data suggest that blockade of glutamate receptors or inhibition of glutamate release has positive effects in many disease models. Glutamate antagonists are already in clinical use for the treatment of Parkinson's disease, epilepsy, spasticity, and neuropathic pain. Overall, glutamate antagonists have not been found clinically effective for neuroprotective treatment of cerebral ischemia or chronic neurodegenerative diseases, with one exception. Side effects of glutamate antagonists can be mainly attributed to central mechanisms and include psychosis, agitation, and disorientation. It is to be hoped that further development of new glutamate antagonists that block disease-relevant subtypes of glutamate receptors will lead to more effective drugs with fewer side effects.

Excitatory Amino Acid Antagonists↗
PubMed2001

[Inflammatory diseases of the spinal cord].

Myelitis is defined as inflammatory disease of the spinal cord irrespective of the underlying aetiology or pathologic-anatomic alterations. It can be caused by direct infections, postinfectious or postvaccinal immunological processes or other (auto)immunological diseases such as multiple sclerosis or systemic vasculitis. The clinical presentation is diverse and varies from temporary sensory deficits to persistent tetraplegia with respiratory insufficiency. Diagnostic work-up must include a thorough anamnesis, clinical-neurological examination, neurophysiological studies, analysis of blood and cerebospinal fluid and neuroradiological investigations. Most important is the spinal MRI: small lesions as well as large lesions throughout the extent of the cord with accompanying edema can be identified reliably. Furthermore, neuroradiological examination can proof or rule out important differential diagnoses. In particular in acute transverse myelitis a quick diagnostic work-up with a spinal MRI is indispensible in order to start an appropriate therapy as soon as possible.

Adolescent↗
PubMed2001

[Gabapentin for therapy of neuropathic pain].

Gabapentin, which has been approved for add-on therapy of focal seizures, is increasingly used for treatment of neuropathic pain. Its analgesic effect is supposed to be due to reduction of glutamatergic transmission, improvement of GABAergic transmission and to binding to voltage-dependent calcium channels. Experimental studies demonstrated an ameliorating effect of gabapentin on neuropathic pain. Placebo-controlled studies revealed an efficacy of gabapentin against pain in diabetic neuropathy and postherpetic neuralgia and in prophylaxis of migraine. Case reports show an analgesic effect of gabapentin in trigeminus neuralgia and in reflex sympathetic dystrophy. The main adverse events are dizziness, ataxia and somnolence. Controlled studies, which compare the efficacy of gabapentin with that of the respective reference drug, are needed to evaluate its importance in treatment of pain.

Acetates↗
PubMed2001

Asymmetries of visual attention after circumscribed subcortical vascular lesions.

OBJECTIVE: To investigate the role of the basal ganglia and the thalamus for basic processes of visuospatial attention METHODS: Fifteen patients with acute circumscribed vascular lesions (10 with haemorrhage and five with infarction) were included in the study. The lesions were confined exclusively to subcortical structures, such as the basal ganglia, internal capsule, and thalamus, which was confirmed by initial CT on the day of referral and MRI taken 14-28 days after clinical onset. These patients were examined with two computerised attentional tasks (one detection and one search task) measuring spatial visual attention. RESULTS: There was a clear attentional asymmetry in patients with right hemispheric lesions (RHLs) in the visual search task. Seven out of eight patients with RHLs tended to be slower and/or missed significantly more target stimuli in the left sided part of a stimulus array consisting of 25 small squares than in right sided parts, although none of these patients showed signs of visual hemineglect in the visual detection task presenting visual information simultaneously to the right and left visual hemispace. All but one of these patients showed lesions in the posterior limb of the internal capsule and the putamen. On the other hand, patients with left hemispheric lesions were not impaired in the search task with only one patient showing more contralesional omissions of target stimuli than could be expected from the behaviour of normal controls. CONCLUSIONS: The results are in line with previous results showing a dominant role of right hemispheric neuronal structures for spatial attention. Furthermore, the data suggest that even with right hemispheric subcortical lesions without cortical involvement deficits in spatial orienting of attention to the left hemispace can be seen. These asymmetries of visual attention in the absence of neglect symptoms are supposed to be caused (1) by a disruption of the motor corticostriato-pallidothalamo-cortical neuronal circuit or (2) by a (partial) disconnection of relevant parts within the posterior attention network-namely, parietal and thalamic structures.

Adult↗
PubMed2001

Unilateral thalamic edema in internal cerebral venous thrombosis: is it mostly left?

Thrombotic occlusion of the internal cerebral veins is a particularly dangerous form of cerebral venous thrombosis (CVT) as it causes venous infarction of the thalami. Because both thalami drain into the vein of Galen and straight sinus, bilateral thalamic involvement is frequently encountered in internal CVT. However, unilateral thalamic edema may also occur, even if all internal cerebral veins are occluded. This suggests collateral venous drainage of the thalami, which is commonly insufficient in internal CVT. Patients with unilateral congestion of the thalamus, including 3 patients reported here, had mostly left-sided involvement, indicating that right-sided unilateral thalamic involvement in CVT may be clinically silent.

Adult↗
PubMed2000

Expression of IL-6 in the ischemic penumbra.

We examined the expression of IL-6 within the ischemic penumbra at various time points after transient (3 h) middle cerebral occlusion (MCA-O) in rats. The animals were killed at 1, 3, 7 or 14 days following operation. Coronal brain sections were processed for immunohistochemistry with antibodies against GFAP, OX 42, IL-6 and Nissl-staining. Glial activation within the penumbra started on day one after ischemia and persisted up to day 14. Expression of IL-6 was not present in sham-operated controls. One day after MCA-O there were several IL-6-positive cells in the penumbra. This expression of IL-6 increased on day 3 and remained elevated up to day 14. According to the shape of the IL-6-positive cells they seem to be microglia and neurons. The present results demonstrate a longlasting expression of IL-6 in the ischemic penumbra.

Animals↗
PubMed2000

[Cerebral vasculitis as a concomitant neurological illness in Crohn's disease].

In Crohn's disease, some concomitant neurological illnesses such as cerebral ischemia following arterial or venous thrombosis, subacute combined degeneration of the spinal cord following malabsorption of vitamin B12 or folic acid, opticus neuropathy, and polyneuropathy have been described. Cerebral vasculitis secondary to Crohn's disease seems to be a very rare phenomenon. We report on three such cases in three female patients (aged 26, 29, and 61 years). All patients became symptomatic with a hemiparesis; one complained additionally of a speech disorder, headache, and intermittent loss of orientation. In CT and MRI scans, multiple lesions were detected; cerebral angiography showed multiple stenoses of middle- and large-sized vessels that were compatible with cerebral vasculitis. Serologic tests concerning vasculitis were inconspicuous at that time. Under anticoagulation (in two cases) and immunosuppressive therapy, neurologic symptoms disappeared. In the following 6 to 12 months, no new neurological symptoms appeared. In two cases, Doppler sonographic controls showed stationary and, in one case, progressive intracranial stenoses. Since autoimmunologically caused inflammatory bowel diseases might be associated with vasculitis of other organs, the appearance of cerebral vasculitis secondary to Crohn's disease is a possible organ manifestation by inflamed vessels.

Adult↗