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Biomedical subjects

Andreas Straube

Publications and source records attributed to Andreas Straube.

At least 19 recordsLinked to original sources
PubMed2006

Bone marrow stromal cells mediate protection through stimulation of PI3-K/Akt and MAPK signaling in neurons.

Application of adult bone marrow stromal cells (BMSC) improves functional outcome in animal models of cerebral ischemia, traumatic brain injury, and spinal cord injury. Accumulating evidence suggests that such functional recovery after BMSC treatment is mediated by enhanced trophic support of the injured neurons and improved neuronal plasticity rather than tissue replacement by bone marrow-derived stem cells. Therefore, the aim of the present study was to explore the potential of non-hematopoietic BMSC to stimulate signaling pathways in neurons that mediate trophic effects and neuroprotection. In primary embryonic rat neurons, BMSC conditioned medium (CM) attenuated staurosporine (STS) or amyloid-beta peptide-induced apoptosis in a concentration-dependent manner. The neuroprotective effect of CM required several hours of pretreatment and was abolished by heating over 90 degrees C. Immunoblot analyses revealed that CM enhanced Erk1/2 and Akt phosphorylation in neurons, and the specific MEK1 inhibitor PD98059 or the phosphoinositide-3 kinase (PI3-K) inhibitor Ly294002 abolished the neuroprotective effect of CM. Further, double-conditioned medium (DCM) obtained from BMSC previously stimulated by medium from STS-challenged neurons showed a more potent anti-apoptotic effect compared to the single-conditioned medium. Overall, these findings demonstrate that BMSC trigger endogenous survival signaling pathways in neurons that mediate protection against apoptotic insults. Moreover, the interaction between stressed neurons and BMSC further amplifies the observed neuroprotective effect.

Animals↗
PubMed2006

Effectiveness of intranasal zolmitriptan in acute cluster headache: a randomized, placebo-controlled, double-blind crossover study.

BACKGROUND: Cluster headache is a form of primary headache in which attacks are rapid in onset with very severe pain. The mainstays of acute therapy are inhaled oxygen and sumatriptan succinate injection. OBJECTIVE: To evaluate zolmitriptan nasal spray in the acute treatment of cluster headache. METHODS: Ninety-two patients, aged 40 +/- 10 years (mean +/- SD) (80 men and 12 women), with International Headache Society-defined cluster headache were randomized into a placebo-controlled, double-blind crossover study. Patients treated 3 headache attacks using placebo for 1 attack, 5 mg of zolmitriptan nasal spray (ZNS5) for 1 attack, and 10 mg of zolmitriptan nasal spray for 1 attack. The primary end point was headache relief at 30 minutes, defined as reduction from moderate, severe, or very severe pain to no or mild pain. The study was approved by the appropriate ethics committees. RESULTS: Sixty-nine patients were available for an intention-to-treat analysis. The 30-minute headache relief rates were placebo, 21%; ZNS5, 40%; and ZNS10, 62%. Modeling the response as a binary outcome, the Wald test was significant for the overall regression (chi(2)(1) = 29.4; P<.001), with both ZNS5 and ZNS10 giving significant effects against placebo. Headache relief rates for patients with episodic cluster headache were 30% for placebo, 47% for ZNS5, and 80% for ZNS10, while corresponding rates for patients with chronic cluster headache were 14%, 28%, and 36%, respectively. Zolmitriptan was also well tolerated. CONCLUSION: Five-milligram and 10-mg doses of zolmitriptan intranasal spray are effective within 30 minutes and well tolerated in the treatment of acute cluster headache. Trial Registration controlled-trials.com Identifier ISCRTN27362692.

Acute Disease↗
PubMed2006

Vascular endothelial growth factor A contributes to glioma-induced migration of human marrow stromal cells (hMSC).

OBJECTIVE: It has been demonstrated that murine neural stem cells (mNSCs) and human mesenchymal stroma cells migrate toward experimental gliomas, making stem cells a candidate for cellular carrier systems of anti-glioma therapy. However, few data are available on the factors involved in regulating stem cell migration. The aim of our study was to characterize the migratory and invasive behavior of adult human marrow stromal cells (hMSC) that interact with glioma cells, especially focusing on vascular endothelial growth factor A (VEGF-A)-mediated effects. METHODS: Human MSC were isolated from bone marrow biopsies carried out for hematological indications. The chemokinetic activity of hMSC in response to glioma-conditioned medium as well as VEGF-A was analyzed using a modified Boyden chamber assay. Invasion of hMSC and glioma spheroids was investigated using confrontational cultures. To provide analogous data from a well-described system, invasion of murine C17.2 neural stem cells was assessed. VEGF-A secretion by gliomas and the expression of VEGF-receptor 2 in hMSC were evaluated. RESULTS: Human MSC showed an extensive invasion into glioma spheroids. Glioma-conditioned medium significantly increased hMSC migration and also invasion, driven by chemotaxis. VEGF-A also showed significant pro-migratory and pro-invasive effects on hMSC, but in a reduced fashion compared to glioma-conditioned medium. CONCLUSIONS: Human MSC show intensive migratory and invasive behavior in the presence of glioma cells and glioma-conditioned medium. Among others, VEGF-A seems to be one important factor in enhancing and directing stem cell motility.

Animals↗
PubMed2005

TMS motor cortical brain mapping in patients with complex regional pain syndrome type I.

OBJECTIVE: The motor cortical representation in patients with complex regional pain syndrome type I (CRPS I) was determined under the assumption that the motor cortex undergoes representational adaptations in the course of CRPS. METHODS: A total of 14 patients with CRPS I and a group of healthy subjects without any known neurological symptoms participated in the study. The motor cortical representation, i.e. the size of representation (cm2), motor-evoked potentials (MEP), the calculated volume (cm2 mV), and the center of gravity (CoG) were measured by transcranial magnetic stimulation. Recordings were made of the long extensor muscles of the forearm of the affected and unaffected hand. RESULTS: Analyses of the results revealed a significant asymmetry between the two hemispheres: the motor cortical representation corresponding to the unaffected hand was significantly larger. While the CoG data did not differ statistically between the two hemispheres, the CoG coordinates corresponding to the affected hand indicated a larger variability. CONCLUSIONS: The presence of pain and other CRPS symptoms may induce lasting changes in motor cortical plasticity, as it also does in the sensory cortex. SIGNIFICANCE: This could be of importance in rehabilitative strategies for the sensory motor system in CRPS I patients.

Adolescent↗
PubMed2005

Evaluation of the efficacy of intravenous acetaminophen in the treatment of acute migraine attacks: a double-blind, placebo-controlled parallel group multicenter study.

The efficacy of intravenous acetaminophen (1000mg) in the treatment of acute migraine attacks as an alternative to parenteral application of lysine acetylsalicylate or triptans was investigated, using a multi-center, randomized, double-blind, placebo controlled study design. Migraine diagnosis was made according to the International Headache Society Classification. Sixty patients were included in three headache outpatient centers (Neurology Departments of the Universities of Regensburg, Münster and München). In the acute migraine attack patients were treated intravenously with either 1000mg paracetamol (acetaminophen) or placebo. The primary end point was pain-free after 2h. Secondary efficacy criteria were pain-free after 24h or pain relief after 2hours and after 24hours. With regard to the efficacy criteria, 37% of patients reported pain relief or painfree after two hours, 12 patients after treatment with acetaminophen and 10 patients after treatment with placebo. Out of these, 3 patients in the acetaminophen and 4 patients in the placebo group were painfree. After 24hours 86% of the patients reported pain relief: 24 treated with acetaminophen and 27 treated with placebo. The results indicate, that 1000mg intravenous acetaminophen is not superior to placebo in treating severe acute migraine attacks.

Acetaminophen↗
PubMed2005

Pharmacology of vertigo/nystagmus/oscillopsia.

PURPOSE OF REVIEW: To describe recent developments in the pharmacological treatment of vertigo and nystagmus while focusing on vestibular neuritis, Meniere's disease, downbeat nystagmus, periodic alternating nystagmus, acquired pendular nystagmus, and superior oblique myokymia. RECENT FINDINGS: In the last 2 years several studies have been published on possible pharmacological treatment options for nystagmus and oscillopsia. In the treatment of vestibular neuritis two studies showed that cortisone treatment was effective for restoring labyrinthine function. This benefit seems more likely if treatment is started within the first 2 days of onset. For recurrent vertigo attacks due to Meniere's disease, the titration technique with daily or weekly doses of intratympanic gentamicin until onset of vestibular symptoms, change in vertigo or hearing loss rated best for complete vertigo control. A new pharmacological treatment option for downbeat nystagmus is the administration of potassium channel blockers (e.g. 4-aminopyridine). They are thought to reinforce the inhibitory action of cerebellar Purkinje cells. Several case reports have proven the beneficial effect of baclofen on periodic alternating nystagmus, of gabapentin and memantine on acquired pendular nystagmus, and of carbamazepine and gabapentin on superior oblique myokymia. SUMMARY: There have been several new developments in the treatment of nystagmus and vertigo over the last 2 years. These include potassium channel blockers for the treatment of downbeat nystagmus, early cortisone treatment to improve recovery of the labyrinth function in vestibular neuritis, and intratympanic gentamicin treatment for Meniere's disease. Other pharmacological treatment options are baclofen for periodic alternating nystagmus, gabapentin and memantine for acquired pendular nystagmus, and carbamazepine for superior oblique myokymia.

Amines↗
PubMed2005

Calcineurin inhibitor-induced headache: clinical characteristics and possible mechanisms.

OBJECTIVE: To classify the headache syndromes under treatment with calcineurin inhibitors and to investigate whether the latter influence the nitric oxide production of human brain microvascular cells (HBMEC). BACKGROUND: Single cases of cyclosporine-induced headaches have been reported. Since calcineurin inhibitors are known to influence the renal metabolism of NO, a key molecule in tension-type headache and migraine, we were interested whether calcineurin inhibitors might change NO metabolism in HBMEC as well. DESIGN AND METHODS: Headache symptoms of 74 patients receiving cyclosporine and/or tacrolimus for organ transplantation were retrospectively assessed. Furthermore, the effect of cyclosporine and tacrolimus on nitric oxide production in human brain microvascular endothelial cells was investigated after incubation. RESULTS: Only 18 of the 74 patients reported no headache 1-36 months after liver, lung, or bone-marrow transplantation, 28 reported a new headache, and 17 an increase in the frequency or intensity of a pre-existing headache. The headache was generally classified as migraine without aura (IHS 1.1) or migraine-like headache (IHS 1.6). Furthermore, we found significantly increased NO production after co-incubation of calcineurin inhibitors with human brain microvascular endothelial cells. CONCLUSION: The pathophysiological mechanism of these headaches may be connected with an endothelial dysfunction in terms of increased production of NO.

Adult↗
PubMed2005

Effects of conditioning peripheral repetitive magnetic stimulation in patients with complex regional pain syndrome.

OBJECTIVES: We tested whether repetitive magnetic stimulation (rMS) induces an afferent input to the spinocerebral tract in patients with complex regional pain syndrome (CRPS). METHODS: Cortical and spinal motor evoked potentials (cMEP and sMEP), as well as the contra- and ipsilateral silent period (cCSP and iCSP), were recorded in patients with CRPS type I before and after conditioning rMS, applied at cervical nerve roots innervating affected muscles. Patients were compared with a group of healthy subjects. RESULTS: In the group of patients we found that cMEP amplitudes were always significantly smaller for both hemispheres. In the group of healthy subjects we found a significant prolongation of the cCSP and iCSP after rMS. This was absent in patients. SMEP were always unchanged in both groups. DISCUSSION: This led us to the explanation that the afferent input to the motor cortical system in CRPS patients is less effective than in healthy subjects.

Adult↗
PubMed2005

Nystagmus: an update on treatment in adults.

Recent developments in the treatment of nystagmus in adults have changed the traditional approach to such illnesses as benign paroxysmal positional vertigo, vestibular neuritis, Meniere's disease, superior canal dehiscence syndrome, vestibular paroxysmia, superior oblique myokymia, downbeat/upbeat nystagmus and acquired pendular nystagmus, as well as periodic alternating nystagmus. Treatments reported to suppress nystagmus, with tolerable side effects, are now available for some of these syndromes. Due to the absence of large controlled studies, however, treatment recommendations rest only on class C evidence.

Adult↗
PubMed2005

Reduction of spastic tone increase induced by peripheral repetitive magnetic stimulation is frequency-independent.

Repetitive magnetic stimulation is able to reduce spastic tone increase after applying it at the spinal cord. It was also found to induce frequency-dependent changes in H-reflex. In a small pilot investigation we stimulated a patient with severe spasticity of the lower limbs and applied different stimulation frequencies. The aim was to look for a clinical measurable effect of spastic reduction depending on the applied frequency. We were unable to show such a dependency, but could confirm the spastic-reducing effects of a peripheral repetitive magnetic stimulation using supratheshold intensities.

Evoked Potentials, Motor↗
PubMed2004

Impaired temporal prediction and eye-hand coordination in patients with cerebellar lesions.

This study investigated the effect of cerebellar lesions on temporal prediction and coordination in eye and hand movements. Nine patients with cerebellar lesions were compared to controls while they made saccades with and without simultaneous pointing movements towards a target that was either temporally predictable or non-predictable. The direction and amplitude of the target step was always predictable. Patients made much more early and late saccades than controls, but an equal amount of visually triggered saccades. This suggests that inappropriate saccades could be suppressed during the preparation of a goal-directed saccade. Hand movement frequency did not differ between both groups. Thus, cerebellar lesions can induce inappropriate saccades more easily than inappropriate hand movements. Controls, but not patients, generated visually triggered saccades of shorter latencies when the target was temporally predictable. Thus, the patients could not use information about target timing to synchronise visually triggered saccades with the target. They could, however, use this information to improve the suppression of inappropriate saccades. Regarding coordination, patients showed impairments in synchronising saccades with hand movements. Nevertheless, hand movements led to an enhancement of anticipatory saccades in patients as in controls. Moreover, hand movements and temporal predictability affected saccadic accuracy in both groups similarly. These results suggest that cerebellar lesions do not generally prevent access to temporal information on the rhythm of a target sequence or the timing of a planned hand movement. More specifically, the cerebellum seems to be crucial for synchronizing saccades with such learned or planned temporal events.

Adult↗
PubMed2004

Predictive strategies in interception tasks: differences between eye and hand movements.

To investigate how the sensorimotor systems of eye and hand use position, velocity, and timing information of moving targets, we conducted a series of three experiments. Subjects performed combined eye-hand catch-up movements toward visual targets that moved with step-ramp-like velocity profiles. Visual feedback of the hand was prevented by blanking the target at the onset of the hand movement. A multiple regression was used to determine the effects of position, velocity, and timing accessed before each movement on the movement amplitudes of eye and hand. The following results were obtained: 1. The predictive strategy of eye movements could be modeled by a linear regression on the basis of the position error and the target velocity. This was not the case for hand movements, for which there was a significant partial correlation between the movement amplitude and the product of target velocity and movement duration. This correlation was not observed for eye movements suggesting that the predictive strategy of hand movements takes movement duration into account, in contrast to the strategy used in eye movements. 2. To determine whether the movement amplitudes of eye and hand depend on a categorical classification between a discrete number of movement types, we compared an experiment in which target position and velocity were distributed continuously with an experiment using only four different combinations of target position and velocity. No systematic differences between these experiments were observed. This shows that the system output is a function of continuous, interval-scaled variables rather than a function of discrete categorical variables. 3. We also analyzed the component of the movement amplitudes not explained by the regression, i.e., the residual error. The residual errors between subsequent trials were correlated more strongly for eye than for hand movements, suggesting that short-term temporal fluctuations of the predictive strategy were stronger for the eye than for the hand.

Adult↗
PubMed2004

Severe symptomatic aseptic chemical meningitis following myelography: the role of procalcitonin.

Symptomatic aseptic, chemical meningitis is a rare complication of myelography. Its acute clinical course and standard laboratory findings are indistinguishable from those of bacterial meningitis. The authors present a case of severe postmyelographic chemical meningitis and compare CSF and serum inflammatory markers to a group of seven patients with proven bacterial meningitis. As in viral meningitis, procalcitonin might be able to discriminate between bacterial and chemical causes of CNS inflammation.

Adult↗
PubMed2004

Cerebral endothelial expression of adhesion molecules in mice with chronic graft-versus-host disease.

BACKGROUND AND PURPOSE: Graft-versus-host disease (GvHD) is a major complication after allogeneic bone marrow transplantation (BMT). The theory that the central nervous system (in addition to the peripheral nervous system) participates in GvHD has been supported by detection of cerebral lymphomononuclear infiltrates in experimental GvHD and the observation of cerebral angiitis-like disease in patients with chronic GvHD. METHODS: In a murine BMT model, we investigated the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on cerebral endothelium after allogeneic and syngeneic transplantation. Through the use of ICAM-1-knockout mice, the effect of ICAM-1 deficiency on cellular infiltration was evaluated. As an indicator of enhanced apoptotic cell death, we examined the cerebral expression of Fas antigen (Fas), the occurrence of the poly-ADP ribose polymerase p85 fragment, and the distribution of TUNEL positive-stained cells. RESULTS: In close correlation with earlier findings of cerebral infiltration in the same animals, we found cerebral endothelial upregulation of ICAM-1 and especially of VCAM-1 in allogeneic recipients compared with syngeneic animals without GvHD and unmanipulated controls. In ICAM-1-knockout mice, leukocytic infiltration did not differ from that in wild-type animals. Neither cerebral histopathologic changes nor an apoptotic effect of cellular infiltrates on brain parenchyma could be detected. CONCLUSIONS: In this model of experimental GvHD, VCAM-1 may play a critical role in leukocyte recruitment into the central nervous system of animals with chronic GvHD.

Animals↗
PubMed2004

Central poststroke pain and reduced opioid receptor binding within pain processing circuitries: a [11C]diprenorphine PET study.

Based on concepts that endogenous opioids participate in neural transmission of pain, the present study in central poststroke pain (CPSP) patients investigated changes in opioid receptor (OR) binding in neural structures centrally involved in the processing of pain. Five patients with central pain after lesions in the brain stem, thalamus or parietal cortex and twelve healthy volunteers underwent a [11C]diprenorphine positron emission tomography study. Binding potentials were calculated using a reference region model in all subjects. Statistical parametric mapping was applied for t-statistical analysis on voxel-basis. Binding potential values for each individual were extracted from a volume of interest at each identified significant peak. Spectral analysis was applied for quantification of global values. Significant regional reduced 11C-diprenorphine binding (corrected for multiple tests) was detected in contralateral thalamus, parietal, secondary somatosensory, insular and lateral prefrontal cortices, and along the midline in anterior cingulate, posterior cingulate and midbrain gray matter. Individual extracted binding values disclosed a reduced binding in these regions in all patients independent from the particular lesion site. The poststroke pain syndrome is associated with a characteristic pattern of reduced OR binding within the neural circuitry processing pain. It is suggested that an imbalance of excitatory-inhibitory mechanisms in certain brain structures, as evidenced in decreased [11C]diprenorphine binding, is one of the causes or the consequences of poststroke pain.

Aged↗