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52. Preclinical investigation on the efficacy of NR4A1-agonist Cytosporon-B for the treatment of ischemic stroke

Author

Strecker, Jan-Kolja, Minnerup, Jens, Klotz, Luisa, Hermann, Dirk, and Hagemann, Nina

Subjects
Stroke, Preclinical study, Neuroscience and Neurobiology, Nuclear receptors, Medicine and Health Sciences, Cytosporone-B, Life Sciences, NR4A1, Neutrophil Granulocytes
Abstract

Background Immune cell immigration and activation play a central role within the pathophysiology of ischemic stroke. In a recent preclinical study, we demonstrated that the nuclear receptor NR4A1 has a potential protective role within the pathophysiology of cerebral ischemia. NR4A1-deficient mice subjected to experimental stroke (middle cerebral artery occlusion, MCAO) develop an increased neutrophil influx, increased brain damage and worsened functional outcome. In an extended gain-of-function experiment, we now aim to clarify whether NR4A1-activation using the NR4A1-specific ligand Cytosporone-B results in enhanced functional recovery and reduced tissue damage in the ischemic rodent brain. Preliminary data from experiments in male mice indicate that activation of NR4A1 results in reduced numbers of intracerebral neutrophil granulocytes, improved functional recovery and reduced tissue damage. In order to fulfill fundamental quality standards for preclinical studies, these findings shall now be validated in a bicentric study. For this purpose, experiments will be repeated at the original research site (University of Muenster, Germany) in female mice and subsequently in both male and female mice at a second study-center (University Hospital Essen, Germany). Assignment to groups (placebo versus active substance) will be performed with a random number generator (GraphPad Prism - assign subjects to groups). Both, drug and placebo units will be coded in a blinded manner and provided by the Muenster site. Subsequent functional testing, evaluation of functional data and determination of infarct volumes will be performed in a blinded fashion. Unblinding as well as group-assignment will be performed after data collection. Infarct volume will be used as the primary outcome measure; functional recovery as a secondary outcome measure. In addition, histological analyses will be performed at the end of the proposed project to decipher the role of NR4A1 activation on potentially protective / regenerative neutrophils. In order to fulfill fundamental requirements of preclinical trials, the following protocol has been established: harmonization of experimental protocols among both study centers, a priori sample size calculation, randomization of the treatment groups and blinding of all investigators. Cytosporone-B treatment Cytosporone-B or the corresponding placebo (16.5% DMSO in PBS) will be applied to wildtype mice (13 mg/kg body weight, i.p.) 3h after induction of reperfusion. Middle cerebral artery occlusion Occlusion of the middle cerebral artery (MCAO) will be induced in anesthetized mice under maintenance of 37˚C body temperature during the whole procedure. After midline neck incision, the left common artery and carotid bifurcation will be exposed and the external and proximal left common arteries will be ligated subsequently. Retrograde perfusion of the left common carotid artery will be transiently interrupted using a microvascular clip. The common carotid artery will then be incised using a micro-dissecting scissors, and a silicon-coated 8–0 nylon monofilament (701956PK5Re or 702056PK5Re, Doccol Corporation, Sharon, MA) is going to be advanced into the middle cerebral artery. Following 30 minutes of MCA occlusion, the filament will be retracted to allow reperfusion of the MCA. Functional testing For comparison of sensorimotor deficits the foot fault test will be used. In the foot fault test, the animals are placed individually on an elevated 10-mm square wire mesh (total grid area of 40 cm x 40 cm) and are subsequently videotaped while walking freely for 2 minutes. The number of foot faults as well as the total number of total steps is counted. The percentage of foot faults is then calculated as number of foot faults of the affected limb / number of total steps of the affected limb*100. Inclusion criteria: - Duration of the MCAO procedure ≤ 60 minutes. - Sufficient occlusion of the middle cerebral artery for 30 minutes. - Successful application of the placebo / agent. Exclusion criteria: - Duration of the MCAO procedure > 60 minutes. - Insufficient occlusion of the middle cerebral artery - Intraoperative bleeding - Animal is circling after MCAO - Weight loss of ≥ 20% - Persistent abnormal posture Based on our results following Cytosporon-B application (3 hours after MCAO) in male mice (placebo infarctvolume 39.85±11.6 vs. Cytosporon-B infarctvolume 24.7±14.1), the following animal numbers were calculated (GPower 3.1.9.2): t tests - Means: Wilcoxon-Mann-Whitney test (two groups) Analysis: A priori: Compute required sample size Input Tail(s) = One Parent distribution = Normal Effect size d = 1.191 α err prob = 0.05 Power (1-β err prob) = 0.8 Allocation ratio N2/N1 = 1 Output: Noncentrality parameter δ = 2.60 Critical t = 1.74 Df = 17.1 Sample size group 1 = 10 Sample size group 2 = 10 Total sample size = 20 Actual power = 0.803 Group size is n=10. Date of registration: 03 January 2023 Study start date: 23 January 2023 Anticipated completion date: 31 May 2023 Country: Germany Funding: This study is funded by the Deutsche Forschungsgemeinschaft (CRC TRR332 TP B2) Prelimininary data has been published at https://www.biorxiv.org/content/10.1101/2022.02.27.482146v1 No conflicts of interest are to report. Contact details for further information: jan.strecker@ukmuenster.de

Published
2023
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56. Simplified Assessment of Lesion Water Uptake for Identification of Patients within 4.5 Hours of Stroke Onset: An Analysis of the MissPerfeCT Study

Author

Sporns, Peter B., primary, Höhne, Marco, additional, Meyer, Lennart, additional, Krogias, Christos, additional, Puetz, Volker, additional, Thierfelder, Kolja M., additional, Duering, Marco, additional, Kaiser, Daniel, additional, Langner, Sönke, additional, Brehm, Alex, additional, Rotkopf, Lukas T., additional, Kunz, Wolfgang G., additional, Fiehler, Jens, additional, Heindel, Walter, additional, Schramm, Peter, additional, Wiendl, Heinz, additional, Minnerup, Heike, additional, Psychogios, Marios Nikos, additional, Kemmling, André, additional, and Minnerup, Jens, additional

Published
2022
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57. Association of Intraventricular Fibrinolysis With Clinical Outcomes in Intracerebral Hemorrhage: An Individual Participant Data Meta-Analysis

Author

Kuramatsu, Joji B., primary, Gerner, Stefan T., additional, Ziai, Wendy, additional, Bardutzky, Jürgen, additional, Sembill, Jochen A., additional, Sprügel, Maximilian I., additional, Mrochen, Anne, additional, Kölbl, Kathrin, additional, Ram, Malathi, additional, Avadhani, Radhika, additional, Falcone, Guido J., additional, Selim, Magdy H., additional, Lioutas, Vasileios-Arsenios, additional, Endres, Matthias, additional, Zweynert, Sarah, additional, Vajkoczy, Peter, additional, Ringleb, Peter A., additional, Purrucker, Jan C., additional, Volkmann, Jens, additional, Neugebauer, Hermann, additional, Erbguth, Frank, additional, Schellinger, Peter D., additional, Knappe, Ulrich J., additional, Fink, Gereon R., additional, Dohmen, Christian, additional, Minnerup, Jens, additional, Reichmann, Heinz, additional, Schneider, Hauke, additional, Röther, Joachim, additional, Reimann, Gernot, additional, Schwarz, Michael, additional, Bäzner, Hansjörg, additional, Claßen, Joseph, additional, Michalski, Dominik, additional, Witte, Otto W., additional, Günther, Albrecht, additional, Hamann, Gerhard F., additional, Lücking, Hannes, additional, Dörfler, Arnd, additional, Ishfaq, Muhammad Fawad, additional, Chang, Jason J., additional, Testai, Fernando D., additional, Woo, Daniel, additional, Alexandrov, Andrei V., additional, Staykov, Dimitre, additional, Goyal, Nitin, additional, Tsivgoulis, Georgios, additional, Sheth, Kevin N., additional, Awad, Issam A., additional, Schwab, Stefan, additional, Hanley, Daniel F., additional, Huttner, Hagen B., additional, Sansing, Lauren, additional, Matouk, Charles C., additional, Leasure, Audrey, additional, Sobesky, Jan, additional, Bauer, Miriam, additional, Schurig, Johannes, additional, Rizos, Timolaos, additional, Haeusler, Karl Georg, additional, Müllges, Wolfgang, additional, Kraft, Peter, additional, Schubert, Anna-Lena, additional, Stösser, Sebastian, additional, Ludolph, Albert Christian, additional, Nueckel, Martin, additional, Glahn, Jörg, additional, Stetefeld, Henning, additional, Rahmig, Jan, additional, Fisse, Anna Lena, additional, Michels, Peter, additional, Schwert, Henning, additional, Hagemann, Georg, additional, Rakers, Florian, additional, Wöhrle, Johannes C., additional, Alshammari, Fahid, additional, Horn, Markus, additional, Bahner, Dirk, additional, Urbanek, Christian, additional, Palm, Frederick, additional, and Grau, Armin, additional

Published
2022
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58. Association of prothrombin complex concentrate administration and hematoma enlargement in non–vitamin K antagonist oral anticoagulant–related intracerebral hemorrhage

Author

Gerner, Stefan T., Kuramatsu, Joji B., Sembill, Jochen A., Sprügel, Maximilian I., Endres, Matthias, Haeusler, Karl Georg, Vajkoczy, Peter, Ringleb, Peter A., Purrucker, Jan, Rizos, Timolaos, Erbguth, Frank, Schellinger, Peter D., Fink, Gereon R., Stetefeld, Henning, Schneider, Hauke, Neugebauer, Hermann, Röther, Joachim, Claßen, Joseph, Michalski, Dominik, Dörfler, Arnd, Schwab, Stefan, Huttner, Hagen B., Horn, Markus, Bahner, Dirk, Hagemann, Georg, Rakers, Florian, Endres, Matthias, Haeusler, Karl Georg, Sobesky, Jan, Schurig, Johannes, Zweynert, Sarah, Bauer, Miriam, Vajkoczy, Peter, Fink, Gereon R., Dohmen, Christian, Stetefeld, Henning, Schwarz, Michael, Reimann, Gernot, Reichmann, Heinz, Schneider, Hauke, Rahmig, Jan, Gerner, Stefan T., Kuramatsu, Joji B., Bogenreuther, Christina, Sembill, Jochen A., Sprügel, Maximilian I., Hagen, Manuel, Knappe, Ruben, Köhrmann, Martin, Schwab, Stefan, Huttner, Hagen B., Kloska, Stephan P., Dörfler, Arnd, Ringwald, Jürgen, Hamann, Gerhard F., Röther, Joachim, Michels, Peter, Ringleb, Peter A., Purrucker, Jan, Rizos, Timolaos, Witte, Otto W., Günther, Albrecht, Wöhrle, Johannes C., Alshammari, Fahid, Claßen, Joseph, Michalski, Dominik, Grau, Armin, Palm, Frederick, Urbanek, Christian, Schellinger, Peter D., Glahn, Jörg, Knappe, Ulrich J., Wiendl, Heinz, Fisse, Anna Lena, Minnerup, Jens, Erbguth, Frank, Nueckel, Martin, Bäzner, Hansjörg, Schwert, Henning, Ludolph, Albert Christian, Stösser, Sebastian, Neugebauer, Hermann, Volkmann, Jens, Müllges, Wolfgang, Kraft, Peter, and Schubert, Anna‐Lena

Published
2018
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62. Phenobarbital in super‐refractory status epilepticus (PIRATE): A retrospective, multicenter analysis.

Author

Kunst, Stefan, Rojo, Mikel, Schmidbauer, Moritz L., Pelz, Johann O., Mueller, Annekatrin, Minnerup, Jens, Meyer, Lennart, Madžar, Dominik, Reindl, Caroline, Madlener, Marie, Malter, Michael, Neumann, Bernhard, and Dimitriadis, Konstantinos

Subjects
STATUS epilepticus, NOSOCOMIAL infections, PHENOBARBITAL, ANAPHYLAXIS, HOSPITAL mortality
Abstract

Objective: Super‐refractory status epilepticus (SRSE) is an enduring or recurring SE after 24 h or more of general anesthesia. This study aimed to evaluate the efficacy and safety of phenobarbital (PB) for the treatment of SRSE. Methods: This retrospective, multicenter study included neurointensive care unit (NICU) patients with SRSE treated with PB between September 2015 and September 2020 from six participating centers of the Initiative of German NeuroIntensive Trial Engagement (IGNITE) to evaluate the efficacy and safety of PB treatment for SRSE. The primary outcome measure was seizure termination. In addition, we evaluated maximum reached serum levels, treatment duration, and clinical complications using a multivariate generalized linear model. Results: Ninety‐one patients were included (45.1% female). Seizure termination was achieved in 54 patients (59.3%). Increasing serum levels of PB were associated with successful seizure control (per μg/mL: adjusted odds ratio [adj.OR] = 1.1, 95% confidence interval [CI] 1.0–1.2, p <.01). The median length of treatment in the NICU was 33.7 [23.2–56.6] days across groups. Clinical complications occurred in 89% (n = 81) of patients and included ICU‐acquired infections, hypotension requiring catecholamine therapy, and anaphylactic shock. There was no association between clinical complications and treatment outcome or in‐hospital mortality. The overall average modified Rankin scale (mRS) at discharge from the NICU was 5 ± 1. Six patients (6.6%) reached mRS ≤3, of whom five were successfully treated with PB. In‐hospital mortality was significantly higher in patients in whom seizure control could not be achieved. Significance: We observed a high rate in attainment of seizure control in patients treated with PB. Success of treatment correlated with higher dosing and serum levels. However, as one would expect in a cohort of critically ill patients with prolonged NICU treatment, the rate of favorable clinical outcome at discharge from the NICU remained extremely low. Further prospective studies evaluating long‐term clinical outcome of PB treatment as well as an earlier use of PB at higher doses would be of value. [ABSTRACT FROM AUTHOR]

Published
2023
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65. Association of Intraventricular Fibrinolysis With Clinical Outcomes in Intracerebral Hemorrhage: An Individual Participant Data Meta-Analysis

Author

Kuramatsu, Joji B., Gerner, Stefan T., Ziai, Wendy, Bardutzky, Juergen, Sembill, Jochen A., Spruegel, Maximilian, I, Mrochen, Anne, Koelbl, Kathrin, Ram, Malathi, Avadhani, Radhika, Falcone, Guido J., Selim, Magdy H., Lioutas, Vasileios-Arsenios, Endres, Matthias, Zweynert, Sarah, Vajkoczy, Peter, Ringleb, Peter A., Purrucker, Jan C., Volkmann, Jens, Neugebauer, Hermann, Erbguth, Frank, Schellinger, Peter D., Knappe, Ulrich J., Fink, Gereon R., Dohmen, Christian, Minnerup, Jens, Reichmann, Heinz, Schneider, Hauke, Roether, Joachim, Reimann, Gernot, Schwarz, Michael, Baezner, Hansjoerg, Classen, Joseph, Michalski, Dominik, Witte, Otto W., Guenther, Albrecht, Hamann, Gerhard F., Luecking, Hannes, Doerfler, Arnd, Ishfaq, Muhammad Fawad, Chang, Jason J., Testai, Fernando D., Woo, Daniel, Alexandrov, Andrei, V, Staykov, Dimitre, Goyal, Nitin, Tsivgoulis, Georgios, Sheth, Kevin N., Awad, Issam A., Schwab, Stefan, Hanley, Daniel F., Huttner, Hagen B., Kuramatsu, Joji B., Gerner, Stefan T., Ziai, Wendy, Bardutzky, Juergen, Sembill, Jochen A., Spruegel, Maximilian, I, Mrochen, Anne, Koelbl, Kathrin, Ram, Malathi, Avadhani, Radhika, Falcone, Guido J., Selim, Magdy H., Lioutas, Vasileios-Arsenios, Endres, Matthias, Zweynert, Sarah, Vajkoczy, Peter, Ringleb, Peter A., Purrucker, Jan C., Volkmann, Jens, Neugebauer, Hermann, Erbguth, Frank, Schellinger, Peter D., Knappe, Ulrich J., Fink, Gereon R., Dohmen, Christian, Minnerup, Jens, Reichmann, Heinz, Schneider, Hauke, Roether, Joachim, Reimann, Gernot, Schwarz, Michael, Baezner, Hansjoerg, Classen, Joseph, Michalski, Dominik, Witte, Otto W., Guenther, Albrecht, Hamann, Gerhard F., Luecking, Hannes, Doerfler, Arnd, Ishfaq, Muhammad Fawad, Chang, Jason J., Testai, Fernando D., Woo, Daniel, Alexandrov, Andrei, V, Staykov, Dimitre, Goyal, Nitin, Tsivgoulis, Georgios, Sheth, Kevin N., Awad, Issam A., Schwab, Stefan, Hanley, Daniel F., and Huttner, Hagen B.

Abstract

Background: In patients with intracerebral hemorrhage (ICH), the presence of intraventricular hemorrhage constitutes a promising therapeutic target. Intraventricular fibrinolysis (IVF) reduces mortality, yet impact on functional disability remains unclear. Thus, we aimed to determine the influence of IVF on functional outcomes. Methods: This individual participant data meta-analysis pooled 1501 patients from 2 randomized trials and 7 observational studies enrolled during 2004 to 2015. We compared IVF versus standard of care (including placebo) in patients treated with external ventricular drainage due to acute hydrocephalus caused by ICH with intraventricular hemorrhage. The primary outcome was functional disability evaluated by the modified Rankin Scale (mRS; range: 0-6, lower scores indicating less disability) at 6 months, dichotomized into mRS score: 0 to 3 versus mRS: 4 to 6. Secondary outcomes included ordinal-shift analysis, all-cause mortality, and intracranial adverse events. Confounding and bias were adjusted by random effects and doubly robust models to calculate odds ratios and absolute treatment effects (ATE). Results: Comparing treatment of 596 with IVF to 905 with standard of care resulted in an ATE to achieve the primary outcome of 9.3% (95% CI, 4.4-14.1). IVF treatment showed a significant shift towards improved outcome across the entire range of mRS estimates, common odds ratio, 1.75 (95% CI, 1.39-2.17), reduced mortality, odds ratio, 0.47 (95% CI, 0.35-0.64), without increased adverse events, absolute difference, 1.0% (95% CI, -2.7 to 4.8). Exploratory analyses provided that early IVF treatment (<= 48 hours) after symptom onset was associated with an ATE, 15.2% (95% CI, 8.6-21.8) to achieve the primary outcome. Conclusions: As compared to standard of care, the administration of IVF in patients with acute hydrocephalus caused by intracerebral and intraventricular hemorrhage was significantly associated with improved functional outcome at 6 months. T

Published
2022

66. The nuclear receptor NR4A1 restrains neutrophil granulocyte mediated brain damage in cerebral ischemia

Author

Strecker, Jan-Kolja, primary, Revenstorff, Julian, additional, Beuker, Carolin, additional, Schmidt-Pogoda, Antje, additional, Hucke, Stephanie, additional, Liebmann, Marie, additional, Vogl, Thomas, additional, Roth, Johannes, additional, Thomas, Christian, additional, Kuhlmann, Tanja, additional, Wiendl, Heinz, additional, Klotz, Luisa, additional, and Minnerup, Jens, additional

Published
2022
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67. Association of intraventricular fibrinolysis with clinical outcomes in intracerebral hemorrhage: an individual participant data meta-analysis

Author

Kuramatsu, Joji B, Gerner, Stefan T, Falcone, Guido J, Selim, Magdy H, Lioutas, Vasileios-Arsenios, Endres, Matthias, Zweynert, Sarah, Vajkoczy, Peter, Ringleb, Peter A, Purrucker, Jan C, Volkmann, Jens, Neugebauer, Hermann, Ziai, Wendy, Erbguth, Frank, Schellinger, Peter D, Knappe, Ulrich J, Fink, Gereon R, Dohmen, Christian, Minnerup, Jens, Reichmann, Heinz, Schneider, Hauke, Röther, Joachim, Reimann, Gernot, Bardutzky, Jürgen, Schwarz, Michael, Bäzner, Hansjörg, Claßen, Joseph, Michalski, Dominik, Witte, Otto W, Günther, Albrecht, Hamann, Gerhard F, Lücking, Hannes, Dörfler, Arnd, Ishfaq, Muhammad Fawad, Sembill, Jochen A, Chang, Jason J, Testai, Fernando D, Woo, Daniel, Alexandrov, Andrei V, Staykov, Dimitre, Goyal, Nitin, Tsivgoulis, Georgios, Sheth, Kevin N, Awad, Issam A, Schwab, Stefan, Sprügel, Maximilian I, Hanley, Daniel F, Huttner, Hagen B, Collaborators, Sansing, Lauren, Matouk, Charles C, Leasure, Audrey, Sobesky, Jan, Bauer, Miriam, Schurig, Johannes, Rizos, Timolaos, Mrochen, Anne, Haeusler, Karl Georg, Müllges, Wolfgang, Kraft, Peter, Schubert, Anna-Lena, Stösser, Sebastian, Ludolph, Albert, Nueckel, Martin, Glahn, Jörg, Stetefeld, Henning, Rahmig, Jan, Kölbl, Kathrin, Fisse, Anna Lena, Michels, Peter, Schwert, Henning, Hagemann, Georg, Rakers, Florian, Wöhrle, Johannes C, Alshammari, Fahid, Horn, Markus, Bahner, Dirk, Urbanek, Christian, Ram, Malathi, Palm, Frederick, Grau, Armin, and Avadhani, Radhika

Subjects
Advanced and Specialized Nursing, drug therapy [Cerebral Hemorrhage], Fibrinolysis, diagnostic imaging [Cerebral Hemorrhage], intracerebral hemorrhage, mortality, Observational Studies as Topic, Treatment Outcome, Fibrinolytic Agents, standard of care, Drainage, Humans, Neurology (clinical), methods [Drainage], ddc:610, Cardiology and Cardiovascular Medicine, hydrocephalus, Cerebral Hemorrhage, Hydrocephalus
Abstract

Background: In patients with intracerebral hemorrhage (ICH), the presence of intraventricular hemorrhage constitutes a promising therapeutic target. Intraventricular fibrinolysis (IVF) reduces mortality, yet impact on functional disability remains unclear. Thus, we aimed to determine the influence of IVF on functional outcomes. Methods: This individual participant data meta-analysis pooled 1501 patients from 2 randomized trials and 7 observational studies enrolled during 2004 to 2015. We compared IVF versus standard of care (including placebo) in patients treated with external ventricular drainage due to acute hydrocephalus caused by ICH with intraventricular hemorrhage. The primary outcome was functional disability evaluated by the modified Rankin Scale (mRS; range: 0–6, lower scores indicating less disability) at 6 months, dichotomized into mRS score: 0 to 3 versus mRS: 4 to 6. Secondary outcomes included ordinal-shift analysis, all-cause mortality, and intracranial adverse events. Confounding and bias were adjusted by random effects and doubly robust models to calculate odds ratios and absolute treatment effects (ATE). Results: Comparing treatment of 596 with IVF to 905 with standard of care resulted in an ATE to achieve the primary outcome of 9.3% (95% CI, 4.4–14.1). IVF treatment showed a significant shift towards improved outcome across the entire range of mRS estimates, common odds ratio, 1.75 (95% CI, 1.39–2.17), reduced mortality, odds ratio, 0.47 (95% CI, 0.35–0.64), without increased adverse events, absolute difference, 1.0% (95% CI, −2.7 to 4.8). Exploratory analyses provided that early IVF treatment (≤48 hours) after symptom onset was associated with an ATE, 15.2% (95% CI, 8.6–21.8) to achieve the primary outcome. Conclusions: As compared to standard of care, the administration of IVF in patients with acute hydrocephalus caused by intracerebral and intraventricular hemorrhage was significantly associated with improved functional outcome at 6 months. The treatment effect was linked to an early time window

Published
2022
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70. Outcome After Thrombectomy and Intravenous Thrombolysis in Patients With Acute Ischemic Stroke: A Prospective Observational Study

Author

Minnerup, Jens, Wersching, Heike, Teuber, Anja, Wellmann, Jürgen, Eyding, Jens, Weber, Ralph, Reimann, Gernot, Weber, Werner, Krause, Lars Udo, Kurth, Tobias, Berger, Klaus, Homberg, V., Petrovitch, A., Heuser, L., Mönnigs, P., Krogias, C., Wallner, B., Hennigs, S., Ahlers, A., Sahl, H., Ranft, A., Dobis, C., Brassel, F., Nolden-Koch, M., Schmitt, H., Chapot, R., Nordmeyer, H., Schlamann, M., Weimar, C., Busch, F., Busch, E.W., Sigges, E., Ruf, H., Wohlfahrt, K., Karatschai, R., Klein, B., Höhle, T., Haass, A., Nasreldein, A., Büchele, B., Gahn, G., Sterker, M., Hantel, T., Krämer, C., Henningsen, H., Adelt, I., König, M., Schmidt, C., Hofmann, A., Niederstadt, T., Unrath, M., Rehfeldt, T., Fauser, B., Pfeiffer, A., Lowens, S., Stögbauer, F., Staudacher, T., Erdmann, P., Grotemeyer, K.H., Spüntrup, E., Bücke, P., Wienecke, P., Faiss, J., Wolzik-Großmann, M., Brune, N., Isenmann, S., Thomas, C., and Mucha, D.

Published
2016
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73. A preclinical randomized controlled multi-centre trial of anti-interleukin-17A treatment for acute ischaemic stroke.

Author

Gelderblom, Mathias, Koch, Simon, Strecker, Jan-Kolja, Jørgensen, Carina, Garcia-Bonilla, Lidia, Ludewig, Peter, Schädlich, Ines Sophie, Piepke, Marius, Degenhardt, Karoline, Bernreuther, Christian, Pinnschmidt, Hans, Arumugam, Thiruma V., Thomalla, Götz, Faber, Cornelius, Sedlacik, Jan, Gerloff, Christian, Minnerup, Jens, Clausen, Bettina H., Anrather, Josef, and Magnus, Tim

Published
2023
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74. Neutrophils in aging and aging‐related pathologies.

Author

Van Avondt, Kristof, Strecker, Jan‐Kolja, Tulotta, Claudia, Minnerup, Jens, Schulz, Christian, and Soehnlein, Oliver

Subjects
NEUTROPHILS, AGING, LIFE spans, LIFE expectancy, PATHOLOGY
Abstract

Summary: Over the past millennia, life expectancy has drastically increased. While a mere 25 years during Bronze and Iron ages, life expectancy in many European countries and in Japan is currently above 80 years. Such an increase in life expectancy is a result of improved diet, life style, and medical care. Yet, increased life span and aging also represent the most important non‐modifiable risk factors for several pathologies including cardiovascular disease, neurodegenerative diseases, and cancer. In recent years, neutrophils have been implicated in all of these pathologies. Hence, this review provides an overview of how aging impacts neutrophil production and function and conversely how neutrophils drive aging‐associated pathologies. Finally, we provide a perspective on how processes of neutrophil‐driven pathologies in the context of aging can be targeted therapeutically. [ABSTRACT FROM AUTHOR]

Published
2023
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82. Association Between Net Water Uptake and Functional Outcome in Patients With Low ASPECTS Brain Lesions: Results From the I-LAST Study.

Author

Broocks, Gabriel, Meyer, Lukas, Elsayed, Sarah, McDonough, Rosalie, Bechstein, Matthias, Faizy, Tobias Djamsched, Sporns, Peter, Schön, Gerhard, Minnerup, Jens, Kniep, Helge C., Hanning, Uta, Barow, Ewgenia, Schramm, Peter, Langner, Soenke, Nawabi, Jawed, Papanagiotou, Panagiotis, Wintermark, Max, Lansberg, Maarten G., Albers, Gregory W., and Heit, Jeremy J.

Published
2023
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83. CT Hypoperfusion-Hypodensity Mismatch to Identify Patients With Acute Ischemic Stroke Within 4.5 Hours of Symptom Onset

Author

Sporns, Peter B., primary, Kemmling, André, additional, Minnerup, Heike, additional, Meyer, Lennart, additional, Krogias, Christos, additional, Puetz, Volker, additional, Thierfelder, Kolja, additional, Duering, Marco, additional, Kaiser, Daniel, additional, Langner, Soenke, additional, Massoth, Christina, additional, Brehm, Alex, additional, Rotkopf, Lukas, additional, Kunz, Wolfgang G., additional, Karch, André, additional, Fiehler, Jens, additional, Heindel, Walter, additional, Schramm, Peter, additional, Royl, Georg, additional, Wiendl, Heinz, additional, Psychogios, Marios, additional, and Minnerup, Jens, additional

Published
2021
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85. A preclinical randomized multicenter trial of anti-IL-17A treatment for acute ischemic stroke

Author

Gelderblom, Mathias, primary, Koch, Simon, additional, Strecker, Jan-Kolja, additional, Jørgensen, Carina, additional, Garcia-Bonilla, Lidia, additional, Ludewig, Peter, additional, Bernreuther, Christian, additional, Pinnschmidt, Hans, additional, Arumugam, Thiruma V., additional, Thomalla, Goetz, additional, Faber, Cornelius, additional, Sedlacik, Jan, additional, Gerloff, Christian, additional, Minnerup, Jens, additional, Clausen, Bettina H., additional, Anrather, Josef, additional, and Magnus, Tim, additional

Published
2021
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86. Reversible Ischemic Lesion Hypodensity in Acute Stroke CT Following Endovascular Reperfusion

Author

Broocks, Gabriel, primary, McDonough, Rosalie, additional, Meyer, Lukas, additional, Bechstein, Matthias, additional, Kniep, Helge, additional, Schön, Gerhard, additional, Nawka, Marie Teresa, additional, Fiehler, Jens, additional, Hanning, Uta, additional, Sporns, Peter, additional, Barow, Ewgenia, additional, Minnerup, Jens, additional, and Kemmling, Andre, additional

Published
2021
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89. The impact of lesion location and lesion size on poststroke infection frequency

Author

Minnerup, Jens, Wersching, Heike, Brokinkel, Benjamin, Dziewas, Rainer, Heuschmann, Peter Ulrich, Gunther Nabavi, Darius, Ringelstein, Erich Bernd, Schabitz, Wolf-Rudiger, and Ritter, Martin Andreas

Subjects
Stroke (Disease) -- Complications and side effects, Stroke (Disease) -- Care and treatment, Stroke (Disease) -- Research, Infection -- Distribution, Infection -- Research, Company distribution practices, Health, Psychology and mental health
Published
2010

91. Natural Killer Cells Are Present in Rag1−/− Mice and Promote Tissue Damage During the Acute Phase of Ischemic Stroke

Author

Rolfes, Leoni, primary, Ruck, Tobias, additional, David, Christina, additional, Mencl, Stine, additional, Bock, Stefanie, additional, Schmidt, Mariella, additional, Strecker, Jan-Kolja, additional, Pfeuffer, Steffen, additional, Mecklenbeck, Andreas-Schulte, additional, Gross, Catharina, additional, Gliem, Michael, additional, Minnerup, Jens, additional, Schuhmann, Michael K., additional, Kleinschnitz, Christoph, additional, and Meuth, Sven G., additional

Published
2021
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92. Clinical Diffusion Mismatch to Select Pediatric Patients for Embolectomy 6 to 24 Hours After Stroke An Analysis of the Save ChildS Study

Author

Sporns, Peter B., Psychogios, Marios-Nikos, Straeter, Ronald, Hanning, Uta, Minnerup, Jens, Chapot, Rene, Henkes, Hans, Henkes, Elina, Grams, Astrid, Dorn, Franziska, Nikoubashman, Omid, Wiesmann, Martin, Bier, Georg, Weber, Anushe, Broocks, Gabriel, Fiehler, Jens, Brehm, Alex, Kaiser, Daniel, Yilmaz, Umut, Morotti, Andrea, Marik, Wolfgang, Nolz, Richard, Jensen-Kondering, Ulf, Braun, Michael, Schob, Stefan, Beuing, Oliver, Goetz, Friedrich, Trenkler, Johannes, Turowski, Bernd, Mohlembruch, Markus, Wendl, Christina, Schramm, Peter, Musolino, Patricia L., Lee, Sarah, Schlamann, Marc, Radbruch, Alexander, Karch, Andre, Rubsamen, Nicole, Wildgruber, Moritz, Kemmling, Andre, Sporns, Peter B., Psychogios, Marios-Nikos, Straeter, Ronald, Hanning, Uta, Minnerup, Jens, Chapot, Rene, Henkes, Hans, Henkes, Elina, Grams, Astrid, Dorn, Franziska, Nikoubashman, Omid, Wiesmann, Martin, Bier, Georg, Weber, Anushe, Broocks, Gabriel, Fiehler, Jens, Brehm, Alex, Kaiser, Daniel, Yilmaz, Umut, Morotti, Andrea, Marik, Wolfgang, Nolz, Richard, Jensen-Kondering, Ulf, Braun, Michael, Schob, Stefan, Beuing, Oliver, Goetz, Friedrich, Trenkler, Johannes, Turowski, Bernd, Mohlembruch, Markus, Wendl, Christina, Schramm, Peter, Musolino, Patricia L., Lee, Sarah, Schlamann, Marc, Radbruch, Alexander, Karch, Andre, Rubsamen, Nicole, Wildgruber, Moritz, and Kemmling, Andre

Abstract

Objective To determine whether thrombectomy is safe in children up to 24 hours after onset of symptoms when selected by mismatch between clinical deficit and infarct. Methods A secondary analysis of the Save ChildS Study (January 2000-December 2018) was performed, including all pediatric patients (<18 years) diagnosed with arterial ischemic stroke who underwent endovascular recanalization at 27 European and United States stroke centers. Patients were included if they had a relevant mismatch between clinical deficit and infarct. Results Twenty children with a median age of 10.5 (interquartile range [IQR] 7-14.6) years were included. Of those, 7 were male (35%), and median time from onset to thrombectomy was 9.8 (IQR 7.8-16.2) hours. Neurologic outcome improved from a median Pediatric NIH Stroke Scale score of 12.0 (IQR 8.8-20.3) at admission to 2.0 (IQR 1.2-6.8) at day 7. Median modified Rankin Scale (mRS) score was 1.0 (IQR 0-1.6) at 3 months and 0.0 (IQR 0-1.0) at 24 months. One patient developed transient peri-interventional vasospasm; no other complications were observed. A comparison of the mRS score to the mRS score in the DAWN and DEFUSE 3 trials revealed a higher proportion of good outcomes in the pediatric compared to the adult study population. Conclusions Thrombectomy in pediatric ischemic stroke in an extended time window of up to 24 hours after onset of symptoms seems safe and neurologic outcomes are generally good if patients are selected by a mismatch between clinical deficit and infarct. Classification of Evidence This study provides Class IV evidence that for children with acute ischemic stroke with a mismatch between clinical deficit and infarct size, thrombectomy is safe.

Published
2021

93. Classification of neurological diseases using multi-dimensional CSF analysis.

Author

Gross, Catharina C, Gross, Catharina C, Schulte-Mecklenbeck, Andreas, Madireddy, Lohith, Pawlitzki, Marc, Strippel, Christine, Räuber, Saskia, Krämer, Julia, Rolfes, Leoni, Ruck, Tobias, Beuker, Carolin, Schmidt-Pogoda, Antje, Lohmann, Lisa, Schneider-Hohendorf, Tilman, Hahn, Tim, Schwab, Nicholas, Minnerup, Jens, Melzer, Nico, Klotz, Luisa, Meuth, Sven G, Meyer Zu Hörste, Gerd, Baranzini, Sergio E, Wiendl, Heinz, Gross, Catharina C, Gross, Catharina C, Schulte-Mecklenbeck, Andreas, Madireddy, Lohith, Pawlitzki, Marc, Strippel, Christine, Räuber, Saskia, Krämer, Julia, Rolfes, Leoni, Ruck, Tobias, Beuker, Carolin, Schmidt-Pogoda, Antje, Lohmann, Lisa, Schneider-Hohendorf, Tilman, Hahn, Tim, Schwab, Nicholas, Minnerup, Jens, Melzer, Nico, Klotz, Luisa, Meuth, Sven G, Meyer Zu Hörste, Gerd, Baranzini, Sergio E, and Wiendl, Heinz

Abstract

Although CSF analysis routinely enables the diagnosis of neurological diseases, it is mainly used for the gross distinction between infectious, autoimmune inflammatory, and degenerative disorders of the CNS. To investigate, whether a multi-dimensional cellular blood and CSF characterization can support the diagnosis of clinically similar neurological diseases, we analysed 546 patients with autoimmune neuroinflammatory, degenerative, or vascular conditions in a cross-sectional retrospective study. By combining feature selection with dimensionality reduction and machine learning approaches we identified pan-disease parameters that were altered across all autoimmune neuroinflammatory CNS diseases and differentiated them from other neurological conditions and inter-autoimmunity classifiers that subdifferentiate variants of CNS-directed autoimmunity. Pan-disease as well as diseases-specific changes formed a continuum, reflecting clinical disease evolution. A validation cohort of 231 independent patients confirmed that combining multiple parameters into composite scores can assist the classification of neurological patients. Overall, we showed that the integrated analysis of blood and CSF parameters improves the differential diagnosis of neurological diseases, thereby facilitating early treatment decisions.

Published
2021

95. Characterization of Extracranial Giant Cell Arteritis with Intracranial Involvement and its Rapidly Progressive Subtype

Author

Beuker, Carolin, primary, Wankner, Maximilian Christian, additional, Thomas, Christian, additional, Strecker, Jan‐Kolja, additional, Schmidt‐Pogoda, Antje, additional, Schwindt, Wolfram, additional, Schulte‐Mecklenbeck, Andreas, additional, Gross, Catharina, additional, Wiendl, Heinz, additional, Barth, Peter J., additional, Eckert, Bernd, additional, Meinel, Thomas Raphael, additional, Arnold, Marcel, additional, Schaumberg, Jens, additional, Krüger, Schulamith, additional, Deb‐Chatterji, Milani, additional, Magnus, Tim, additional, Röther, Joachim, additional, and Minnerup, Jens, additional

Published
2021
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96. Classification of neurological diseases using multi-dimensional CSF analysis

Author

Gross, Catharina C, primary, Schulte-Mecklenbeck, Andreas, additional, Madireddy, Lohith, additional, Pawlitzki, Marc, additional, Strippel, Christine, additional, Räuber, Saskia, additional, Krämer, Julia, additional, Rolfes, Leoni, additional, Ruck, Tobias, additional, Beuker, Carolin, additional, Schmidt-Pogoda, Antje, additional, Lohmann, Lisa, additional, Schneider-Hohendorf, Tilman, additional, Hahn, Tim, additional, Schwab, Nicholas, additional, Minnerup, Jens, additional, Melzer, Nico, additional, Klotz, Luisa, additional, Meuth, Sven G, additional, Meyer zu Hörste, Gerd, additional, Baranzini, Sergio E, additional, and Wiendl, Heinz, additional

Published
2021
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