Wolf-Rüdiger Schäbitz

University of Münster, Muenster, North Rhine-Westphalia, Germany

Are you Wolf-Rüdiger Schäbitz?

Claim your profile

Publications (95)507.72 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We investigated whether hyperintensities with a diameter of at least 3, 3.5, and 4 cm and visible on at least 3 slices on diffusion-weighted imaging enables patient selection with an infarct volume of ≥15 mL. Consecutive acute stroke patients were screened for the AXIS2 trial and examined according to a standardized magnetic resonance imaging protocol in 65 sites. Diffusion-weighted lesion diameters were measured and compared with volumetric assessments. Out of 238 patients, 86.2% (N=206) had infarct diameter of at least 3 cm. Volumetric assessments showed infarct volume of ≥15 mL in 157 patients. A cut-off value of 3 cm led to 96.8% sensitivity and 33.3% specificity for predicting lesion volume of ≥15 mL. Analogously, a 3.5 cm cut-off led to 96.8% sensitivity and 50.6% specificity and a 4 cm cut-off led to 91.7% sensitivity and 61.7% specificity. Lesion diameter measures may enable multicentric patient recruitment with a prespecified minimal infarct volume. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00927836. © 2015 American Heart Association, Inc.
    Stroke 03/2015; 46(5). DOI:10.1161/STROKEAHA.114.008115 · 6.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In spite of its high disease burden, there is no specific treatment for multi-infarct dementia. The preclinical evaluation of candidate drugs is limited because an appropriate animal model is lacking. Therefore, we aimed to evaluate whether a mouse model of recurrent photothrombotic stroke is suitable for the preclinical investigation of multi-infarct dementia. Recurrent photothrombotic cortical infarcts were induced in 25 adult C57BL/6 mice. Twenty-five sham-operated animals served as controls. The object recognition test and the Morris water maze test were performed >6 weeks to assess cognitive deficits. Afterward, histological analyses were performed to characterize histopathologic changes associated with recurrent photothrombotic infarcts. After the first infarct, the object recognition test showed a trend toward an impaired formation of recognition memories (P=0.08), and the Morris Water Maze test revealed significantly impaired spatial learning and memory functions (P<0.05). After recurrent infarcts, the object recognition test showed significant recognition memory deficits (P<0.001) and the Morris water maze test demonstrated persisting spatial learning and memory deficits (P<0.05). Histological analyses revealed remote astrogliosis in the hippocampus. Our results show progressive cognitive deficits in a mouse model of recurrent photothrombotic stroke. The presented model resembles the clinical features of human multi-infarct dementia and enables the investigation of its pathophysiological mechanisms and the evaluation of treatment strategies. © 2015 American Heart Association, Inc.
    Stroke 03/2015; 46(4). DOI:10.1161/STROKEAHA.115.008905 · 6.02 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Granulocyte-colony stimulating factor (G-CSF) and bone marrow derived mononuclear cells (BM-MNCs) have both been shown to improve functional outcome following experimental stroke. These effects are associated with increased angiogenesis and neurogenesis. In the present study, we aimed to determine synergistic effects of G-CSF and BM-NMC treatment on long-term structural and functional recovery after photothrombotic stroke. To model the etiology of stroke more closely, we used spontaneously hypertensive (SH) rats in our experiment. Bone marrow derived mononuclear cells transplantation was initiated 1 h after the onset of photothrombotic stroke. Repeated G-CSF treatment commenced immediately after BM-MNC treatment followed by daily injections for five consecutive days. The primary endpoint was functional outcome after ischemia. Secondary endpoints included analysis of neurogenesis and angiogenesis as well as determination of infarct size. Granulocyte-colony stimulating factor treated rats, either in combination with BM-MNC or alone showed improved somatosensory but not gross motor function following ischemia. No beneficial effect of BM-MNC monotherapy was found. Infarct volumes were comparable in all groups. In contrast to previous studies, which used healthy animals, post-stroke neurogenesis and angiogenesis were not enhanced by G-CSF. In conclusion, the combination of G-CSF and BM-MNC was not more effective than G-CSF alone. The reduced efficacy of G-CSF treatment and the absence of any beneficial effect of BM-MNC transplantation might be attributed to hypertension-related morbidity.
    Frontiers in Cellular Neuroscience 12/2014; 8:411. DOI:10.3389/fncel.2014.00411 · 4.18 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Differential diagnosis of severe progressive dementia includes a wide spectrum of inflammatory and neurodegenerative diseases. Particularly challenging is the differentiation of potentially treatable autoimmune encephalitis and Creutzfeldt-Jakob disease. Such a coincidence may indeed complicate the correct diagnosis and influence subsequent treatment.Case presentationA 75-year-old woman was admitted due to rapid progressive cognitive impairment. Her husband observed a temporal disorientation and confusion. The initial neurological examination and an extensive neuropsychological evaluation showed significant impairments in almost all tested cognitive domains. All other neurological functions including motor, sensory and coordinative function were intact. Initial diagnostics included EEG, MRI and lumbar puncture with unspecific results. Complementary blood testing revealed a positive result for antineural antibodies to Contactin-associated protein 2 (CASPR2) and the patient received treatment for CASPR2 autoimmune encephalitis. Further symptoms and results, including 14-3-3 proteins, led to suspected Creutzfeldt-Jakob disease. The postmortem examination supported the diagnosis of a definitive Creutzfeldt-Jakob disease.Conclusion One could argue that global screening for antineural antibodies may lead to a false diagnosis triggering intense and potentially dangerous procedures. We believe, however, that potentially treatable causes of dementia should aggressively sought out and subsequently treated in an attempt to curtail the course of disease and ultimately reduce the rate of mortality.
    BMC Neurology 11/2014; 14(1):227. DOI:10.1186/s12883-014-0227-7 · 2.49 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Eligibility criteria are a key factor for the feasibility and validity of clinical trials. We aimed to develop an online tool to assess the potential effect of inclusion and exclusion criteria on the proportion of patients eligible for an acute stroke trial.
    Stroke 11/2014; 46(1). DOI:10.1161/STROKEAHA.114.007124 · 6.02 Impact Factor
  • Neurology 11/2014; 83(24). DOI:10.1212/WNL.0000000000001072 · 8.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and Purpose-We aimed to determine a possible synergistic effect of granulocyte colony-stimulating factor (G-CSF) and bone marrow-derived mononuclear cells (BM MNC) after stroke in spontaneously hypertensive rats. Methods-Male spontaneously hypertensive rats were subjected to middle cerebral artery occlusion and randomly assigned to daily injection of 50 g/kg G-CSF for 5 days starting 1 hour after stroke (groups 1, 2, and 3) with additional intravenous transplantation of 1.5x10E7 BM MNC per kilogram at 6 hours (group 2) or 48 hours (group 3) after stroke, or control treatment (group 4). Circulating leukocyte counts and functional deficits, infarct volume, and brain edema were repeatedly assessed in the first week and first month. Results-G-CSF treatment led to a significant neutrophilia, to a reversal of postischemic depression of circulating leukocytes, and to a significantly improved functional recovery without affecting the infarct volume or brain edema. BM MNC cotransplantation was neutral after 6 hours, but reversed the functional effect of G-CSF after 48 hours. Short-term investigation of combined G-CSF and BM MNC treatment at 48 hours indicated splenic accumulation of granulocytes and transplanted cells, accompanied by a significant rise of granulocytes in the circulation and the ischemic brain. Conclusions-G-CSF improved functional recovery in spontaneously hypertensive rats, but this effect was abolished by cotransplantation of BM MNC after 48 hours. In the spleen, transplanted cells may hinder the clearance of granulocytes that were massively increased by G-CSF. Increased circulation and infiltration of granulocytes into the ischemic brain may be detrimental for stroke outcome.
    Stroke 07/2014; 45(8). DOI:10.1161/STROKEAHA.113.004460 · 6.02 Impact Factor
  • Source
    Uwe Dietrich, Tilmann Graf, Wolf-Rüdiger Schäbitz
    [Show abstract] [Hide abstract]
    ABSTRACT: We report a case with acute small infarct of the left middle cerebral artery in a 72-year-old man with atrial fibrillation documented by MRI and MR angiography. One hour later, he lost consciousness and CT with CT angiography revealed bilateral hyperdense middle cerebral arteries due to occlusion of the M1 segments. Mechanical thrombectomy of the right middle cerebral artery was successfully performed. During that time, thrombosis on the left side had progressed to carotid T occlusion, which was recanalized as well. The patient had a good outcome with slight aphasia and mild paresis of the left hand and could be transferred to rehabilitation 2 weeks later.
    Case Reports in Neurology 05/2014; 6(2):144-8. DOI:10.1159/000362160
  • Wolf-Rüdiger Schäbitz
    05/2014; 16(5):12-12. DOI:10.1007/s15005-014-0838-y
  • Wolf-Rüdiger Schäbitz, Ulrich Dirnagl
    Stroke 04/2014; 45(6). DOI:10.1161/STROKEAHA.114.005294 · 6.02 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background and purpose: Both the immobilization of the unaffected arm combined with physical therapy (forced arm use, FAU) and voluntary exercise (VE) as model for enriched environment are promising approaches to enhance recovery after stroke. The genomic mechanisms involved in long-term plasticity changes after different means of rehabilitative training post-stroke are largely unexplored. The present investigation explored the effects of these physical therapies on behavioral recovery and molecular markers of regeneration after experimental ischemia. 42 Wistar rats were randomly treated with either forced arm use (FAU, 1-sleeve plaster cast onto unaffected limb at 8/10 days), voluntary exercise (VE, connection of a freely accessible running wheel to cage), or controls with no access to a running wheel for 10 days starting at 48 hours after photothrombotic stroke of the sensorimotor cortex. Functional outcome was measured using sensorimotor test before ischemia, after ischemia, after the training period of 10 days, at 3 and 4 weeks after ischemia. Global gene expression changes were assessed from the ipsi- and contralateral cortex and the hippocampus. FAU-treated animals demonstrated significantly improved functional recovery compared to the VE-treated group. Both were superior to cage control. A large number of genes are altered by both training paradigms in the ipsi- and contralateral cortex and the hippocampus. Overall, the extent of changes observed correlated well with the functional recovery obtained. One category of genes overrepresented in the gene set is linked to neuronal plasticity processes, containing marker genes such as the NMDA 2a receptor, PKC zeta, NTRK2, or MAP 1b. We show that physical training after photothrombotic stroke significantly and permanently improves functional recovery after stroke, and that forced arm training is clearly superior to voluntary running training. The behavioral outcomes seen correlate with patterns and extent of gene expression changes in all brain areas examined. We propose that physical training induces a fundamental change in plasticity-relevant gene expression in several brain regions that enables recovery processes. These results contribute to the debate on optimal rehabilitation strategies, and provide a valuable source of molecular entry points for future pharmacological enhancement of recovery.
    Experimental and Translational Stroke Medicine 02/2014; 6(1):3. DOI:10.1186/2040-7378-6-3
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Bone marrow-derived mononuclear cells (BM-MNCs) were shown to improve the outcome in animal stroke models and clinical pilot studies on BM-MNCs for stroke patients were already conducted. However, relevant aspects of pre-clinical evaluation, such as the use of animals with comorbidities and dose-response studies, were not thoroughly addressed so far. We therefore investigated different BM-MNC doses in the clinical meaningful stroke model of spontaneously hypertensive (SH) rats. Three hours after the onset of transient middle cerebral artery occlusion (MCAO) animals received either one of three syngeneic BM-MNC doses or placebo intravenously. The primary endpoint was the infarct size. Secondary endpoints included functional outcome, mortality, inflammatory processes, and the dose-response relationship. In contrast to previous studies which used healthy animals no beneficial effect of BM-MNCs was found. Infarct volumes, mortality, behavioral outcomes, and the extent of the inflammatory response to cerebral ischemia were comparable in all groups. In conclusion, we could not demonstrate that early BM-MNC treatment improves the outcome after stroke in SH rats. Whether BM-MNCs improve neurological recovery after delayed treatment initiation was not investigated in the present study, but our data indicates that this should be determined in co-morbid animal stroke models before moving to large-scale clinical studies. Future preclinical stroke studies on co-morbid animals should also include groups of healthy animals in order to determine whether negative results can be attributed to the comorbid condition.
    Frontiers in Cellular Neuroscience 01/2014; 7:288. DOI:10.3389/fncel.2013.00288 · 4.18 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite a high incidence of poststroke dementia, there is no specific treatment for this condition. Because the evaluation of poststroke cognitive deficits in animal models of stroke is exceedingly challenging, the preclinical evaluation of candidate drugs is limited. We aimed to explore the impact of small cortical photothrombotic strokes on poststroke cognition, thereby assessing the suitability of this experimental stroke model for the investigation of cognitive impairment after stroke. Photothrombotic cortical infarcts were induced in 19 adult male Wistar rats. Nineteen sham-operated animals served as controls. Using the Morris water maze, we analyzed the impact of photothrombotic stroke on both the acquisition of new memories and the recall of previously acquired memories. The cylinder test, the adhesive tape removal test, and the rotarod test were performed to investigate sensorimotor deficits. Photothrombotic stroke significantly impaired the recall of previously acquired memories (P<0.05), whereas the acquisition of new memories remained largely intact. The analysis of the animals' swimming speed in the water maze and the rotarod test showed no confounding motor impairments after photothrombotic stroke. The adhesive tape removal test and the cylinder test revealed mild sensorimotor deficits in lesioned animals (P<0.05). Photothrombotic cortical infarcts impair the recall of memories acquired before stroke, whereas the formation of new memories remains unimpaired. The observed deficits in the water maze are not confounded by disturbed motor functions. Overall, experimental photothrombotic strokes are well suited for the investigation of specific cognitive impairments after stroke.
    Stroke 12/2013; 45(2). DOI:10.1161/STROKEAHA.113.001907 · 6.02 Impact Factor
  • Armin Schneider, Wolf-Rüdiger Schäbitz, E Bernd Ringelstein
    Stroke 12/2013; 45(1). DOI:10.1161/STROKEAHA.113.003833 · 6.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although several studies have shown beneficial effects of training in animal stroke models, the most effective training strategy and the optimal time to initiate training have not been identified. The present meta-analysis was performed to compare the efficacy of different training strategies and to determine the optimal time window for training in animal stroke models. We searched the literature for studies analyzing the efficacy of training in animal models of ischemic stroke. Training was categorized into forced physical training, voluntary physical training, constraint-induced movement therapy, and skilled reaching training. Two reviewers independently extracted data on study quality, infarct size, and neurological outcome. Data were pooled by means of a meta-analysis. Thirty-five studies with >880 animals were included. A meta-analysis of all treatments showed that training reduced the infarct volume by 14% (95% confidence interval, 2%-25%) and improved the cognitive function by 33% (95% confidence interval, 8%-50%), the neuroscore by 13.4% (95% confidence interval, 1.5%-25.3%), and the running function by 6.6% (95% confidence interval, 1.4%-11.9%). Forced physical training reduced the infarct volume and enhanced the running function most effectively, whereas skilled reaching training improved the limb function most effectively. A meta-regression illustrated that training was particularly efficacious when initiated between 1 and 5 days after stroke onset. Our meta-analysis confirms that training reduces the infarct volume and improves the functional recovery in animal stroke models. Forced physical training and skilled reaching training were identified as particularly effective training strategies. The efficacy of training is time dependent.
    Stroke 10/2013; 45(1). DOI:10.1161/STROKEAHA.113.002048 · 6.02 Impact Factor
  • Holger Reinecke, Christiane Engelbertz, Wolf-Rüdiger Schäbitz
    Stroke 09/2013; 44(10). DOI:10.1161/STROKEAHA.113.001701 · 6.02 Impact Factor
  • Wolf-Rüdiger Schäbitz
    Stroke 07/2013; 44(8). DOI:10.1161/STROKEAHA.113.002228 · 6.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Stroke-induced blood-brain barrier (BBB)-disruption can contribute to further progression of cerebral damage. There is rising evidence for a strong involvement of chemokines in postischemic BBB-breakdown. In a previous study, we showed that monocyte chemoattractant protein-1 (MCP-1)-deficiency results in a markedly reduced inflammatory reaction with decreased levels of interleukin-6, interleukin-1β, and granulocyte colony-stimulating factor after experimental stroke. With MCP-1 as one of the key players in stroke-induced inflammation, in this study, we investigated the influence of MCP-1 on poststroke BBB-disruption as well as transcription/translation of BBB-related genes/proteins after cerebral ischemia. Sixteen wild-type and 16 MCP-1(-/-) mice were subjected to 30 minutes of middle cerebral artery occlusion. By injecting high molecular-tracer, we compared the degree of BBB-disruption after middle cerebral artery occlusion. Real-time polymerase chain reactions and Western blot technique were used to compare tight-junction gene expression, protein secretion, and BBB-leakage. Here, we report that MCP-1-deficiency results in a reduced BBB-leakage and a diminished expression of BBB-related genes occludin, zonula occludens-1, and zonula occludens-2. Real-time polymerase chain reactions and Western blot analysis revealed elevated claudin-5-levels in MCP-1(-/-) animals. MCP-1-deficiency resulted in reduced infarct sizes and an increased vascular accumulation of fluorescein-isothiocyanate-albumin. The results of the study provide further insights into the molecular mechanisms of BBB-opening and may help to better understand the mechanisms of infarct development after cerebral ischemia.
    Stroke 07/2013; 44(9). DOI:10.1161/STROKEAHA.111.000528 · 6.02 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Dissections of the cervical arteries cause about 20% of total juvenile strokes. Approximately 4% of the carotid artery dissections are due to a (poly)trauma such as car accidents. Despite improved diagnostic facilities, traumatic dissections are often underdiagnosed or diagnosed too late due to a lack of awareness of potential initial signs and symptoms. We report here a case of a delayed embolic stroke after a car accident caused by a dissection of the carotid artery and subsequent pseudoaneurysm. To reduce the long-term morbidity or mortality of multiple trauma patients, an early detection of cervical carotid and vertebral dissections is strictly necessary.
    Case Reports in Neurology 01/2013; 5(1):21-5. DOI:10.1159/000347001
  • Sean I Savitz, Wolf-Rüdiger Schäbitz
    Stroke 10/2012; 43(12). DOI:10.1161/STROKEAHA.112.657247 · 6.02 Impact Factor

Publication Stats

2k Citations
507.72 Total Impact Points

Institutions

  • 2006–2015
    • University of Münster
      • Department of Neurology
      Muenster, North Rhine-Westphalia, Germany
  • 2009–2014
    • Evangelic Hospital Bielefeld
      Bielefeld, North Rhine-Westphalia, Germany
  • 2013
    • University of Virginia
      • Department of Physics
      Charlottesville, Virginia, United States
  • 2007–2013
    • Universitätsklinikum Münster
      • Klinik und Poliklinik für Neurologie
      Muenster, North Rhine-Westphalia, Germany
  • 2010
    • Bielefeld University
      Bielefeld, North Rhine-Westphalia, Germany
  • 2003–2009
    • Universität Heidelberg
      • Department of Neurology
      Heidelburg, Baden-Württemberg, Germany
  • 2004
    • Universität Ulm
      Ulm, Baden-Württemberg, Germany