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3. Weaning and extubation failure in myasthenic crisis: a multicenter analysis

Author

Neumann, Bernhard, Angstwurm, Klemens, Dohmen, Christian, Mergenthaler, Philipp, Kohler, Siegfried, Schönenberger, Silvia, Lee, De-Hyung, Gerner, Stefan T., Huttner, Hagen B., Thieme, Andrea, Steinbrecher, Andreas, Dunkel, Juliane, Roth, Christian, Schneider, Hauke, Reichmann, Heinz, Fuhrer, Hannah, Kleiter, Ingo, Schneider-Gold, Christiane, Alberty, Anke, Zinke, Jan, Schroeter, Michael, Linker, Ralf, Meisel, Andreas, Bösel, Julian, and Stetefeld, Henning R.

Published
2024
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9. Intensive heart rhythm monitoring to decrease ischemic stroke and systemic embolism—the Find-AF 2 study—rationale and design

Author

Wachter, Rolf, Gröschel, Klaus, Wasser, Katrin, Uhe, Tobias, Schäbitz, Wolf-Rüdiger, Köhrmann, Martin, Dichgans, Martin, Gröschel, Sonja, Uphaus, Timo, Hahn, Marianne, Zuhorn, Frederic, Wulff, Leonard, Plümer, Jorge, Kok, Lena, Janz, Marcel, Kitsiou, Alkisti, Gehmeyr, Julian, Dabbagh, Alhuda, Huber, Charlotte, Pelz, Johann, Wartenberg, Katja, Michalski, Dominik, Seidel, Mirko, Flissakowski, Oscar, Goschenhofer, Anna, Hussain, Rabia-Basari, Kim, Ina, Kinze, Stephan, Kroneberger, Christian, Lingnau, Michale, Lischewski, Dennis, Muhn, Florian, Rogge, Witold, Schieffer, Miriam, Setayesh-Roonizi, Anuscheh, Sparenberg, Paul, Schertel, Jill Marie, Ringleb, Peter, Purrucker, Jan, Berberich, Anne, Heyse, Miriam, Ungerer, Matthias, Bauer, Gregor, Reichardt, Christine, Etgen, Thorleif, Ebel, Bernhard, Milanković-Eberl, Dragana, Schwarte, Olav, Höcherl, Constanze, Asch, Eric-Manuel, Bojtschuk, Luisa, Frey, Maximilian, Dlouhy, Tomas, Ertl, Michael, Zickler, Philipp Patrick, Beier, Barbara, Braadt, Lino-Dominic, Gabrielyan, Inessa, Kermer, Pawel, Kaste, Matthias, Anter, Ahmed, Stirbulescu, Corina, Meleshchenco, Nataliia, Burgholte, Friederike, Lüers, Claus, Steiner, Thorsten, Cierpinski, Mari-Carmen, Lichti, Bethke, Florian, Bonowski, Lars, Eid, Hassan Abou, Vajda-Medina, Esteban, Probst, Mareike, Essa, Hisham, Frank, Benedikt, Stolte, Benjamin, Milles, Lennart, Soda, Hassan, Hiermann, Erich, Rascher, Renate Weinhardt Alexandra, Stan, Marius, Kääb, Stefan, Kellert, Lars, Dimitriadis, Konstantinos, Kopczak, Anna, Küster, Bettina, Sinner, Moritz, Steiger, Ignaz, Kaffe, Maria, Clauß, Sebastian, Janowitz, Daniel, Thaler, Raffael, Schellinger, Peter, Glahn, Jörg, Schubert, Jan, Jenniges, Simone, Markmann-Boenke, Silke, Putzer, Anne-Sophie, Straeten, Michael Schwarze Vera, Wiemer, Marcus, Kallmünzer, Bernd, Macha, Kosmas, Haupenthal, David, Balk, Stefanie, Kossel, Clara-Sophie, Häusler, Georg, Lehrieder, Dominik, Cidlinsky, Peter, Hametner, Christian, Vogl, Christine, Fischer, Thomas, Huttelmaier, Moritz, Nordbeck, Octavian Maniuc Peter, von Hardenberg, Albrecht, Jünemann, Martin, Braun, Tobias, Viard, Maxime, Gerner, Stefan, Omar, AlHaj, Genau, Sonja, Olbricht, Linus, Wassenberg, Matthias, Langguth, Niklas, Fräbel, Christian, Baumgart, Romy, Kalra, Love-Preet, Diel, Norma, Hoffmann, Frank, Kraft, Andrea, Schönmuth, Bettine, Giebler, Anja, Weber, Lorenz, Grond, Martin, Birringer, Jan, Lichte-Schneider, Sandra, Hütwohl, Daniela, Krause, Lars Udo, Petersen, Martina, Althaus, Katharina, Kirchmeier, Konstantin, Novikova, Liubov, Müller, Susanne, Schellong, Sebastian, Brudzinski, Mirko, Gerk, Ulrich, Palisch, Holger, Heinzel, Frank R., Fett, Jana, Suntha, Avinash, Burian, Katja, Schmitz, Bettina, Gutwinski, Anna, Angermüller, Veronika, Alhammoud, Tameem, Cakiroglu, Hüsniye, Bach, Ullrich, Nabavi, Darius, Offermann, Jens, Crome, Olaf, Dimitrijeski, Boris, Meincke, Carsten, Hamann, Gerhard, Alber, Burkhard, Müller, Robert, Pallesen, Lars-Peder, Pütz, Volker, Hartmann, Christian, Berrouschot, Jörg, Stoll, Anett, Keilitz, Janina, Klunk, Dietrich, Voigt, Roman, Kastrup, Andreas, Schröter, Andreas, Schmucker, Johannes, Pfeilschifter, Waltraud, Krämer, Christoffer, Wiemers, Milena, Simon, Micha, Finke, Alexander, Weiß, Christian, Hobohm, Carsten, Naupold, Katrin, Bley-Renning, Karen, Winter, Sabrina, Poli, Sven, Mengel, Annerose, Poli, Khouloud, Expósito, Alexandra Gómez, Mbroh, Joshua, Tieck, Maria, Rosenkranz, Michael, Boskamp, Stefan, Ritter, Nicolas, Seibel, Lena, Schöps, Christian, Ketzler, Rebecca, Nägele, Herbert, Sydow, Karsten, Kurka, Natalia, Schäfer, Jan Hendrik, Charisse, Daniel, Gruber, Katharina, Kohlhase, Konstantin, Lieschke, Franziska, Operhalski, Felix, Seiler, Alexander, Petzold, Gabor, Bode, Felix Jürgen, Stösser, Sebastian, Meißner, Julius, Ebrahimi, Taraneh, Nordsiek, Julia, Beckonert, Niklas, Weissenborn, Karin, Große, Gerrit Maximilian, Worthmann, Hans, Hennemann, Ann-Katrin, Jochmann, Svenja, Gründahl, Julius, Al-Ayoubi, Jana, Ernst, Johanna, Bähr, Oliver, Gruber, Herbert, Benesch, Sonka, Pollinger, Thomas, Alachkar, Nawar, Busch, Sonia, Butz, Steffi, Forkmann, Mathias, Mahnkopf, Christian, Mischke, Thomas, Schnupp, Steffen, Thomalla, Götz, Deb-Chatterji, Milani, Cheng, Bastian, Gelderblom, Mathias, Hoppe, Julia, Jensen, Märit, Schell, Maximilian, Schlemm, Eckhard, Marquardt, Lars, Kazarians, Haiko, Rheingans, Pia Franziska, Hötzer, Kai, Rose, Dietmar, Neumann-Haefelin, Tobias, Berthel, Jörg, Alijaj, Lirim, Krug, Joachim, Niethammer, Margit, Szöllösi, Géza-Attila, Obermann, Marc, Adochitei, Nicoletta, Strik, Herwig, Lenz, Arne, Steigerwald, Frank, Müller, Jörg, Honermann, Martin, Burgstaller, Marian Christoph, Kollmar, Rainer, Rashid, Maryam, Ganai, Ahmad Ajaz, Ossendorf, Saric, Majda, Tischer, Karl-Heinz, Toluli, Adela, Wollenweber, Frank Arne, Rahban, Laya, Silva, Thais Portugal, Lee, Miri, Grosch, Matthias Julius, Minnerup, Jens, Liman, Jan, Nückel, Martin, Böhm, Magdalena, Weber-Krüger, Mark, Brachmann, Johannes, Laufs, Ulrich, Gelbrich, Götz, Petroff, David, Prettin, Christiane, Schellinger, Peter D., Hamann, Gerhard F., Mende, Meinhard, and Wagner, Marcus

Published
2023
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11. Glutamic acid decarboxylase antibody-associated neurological syndromes: Clinical and antibody characteristics and therapy response

Author

Madlener, Marie, Strippel, Christine, Thaler, Franziska S., Doppler, Kathrin, Wandinger, Klaus P., Lewerenz, Jan, Ringelstein, Marius, Roessling, Rosa, Menge, Til, Wickel, Jonathan, Kellingshaus, Christoph, Mues, Sigrid, Kraft, Andrea, Linsa, Andreas, Tauber, Simone C., Berg, Florian Then, Gerner, Stefan T., Paliantonis, Asterios, Finke, Alexander, Priller, Josef, Schirotzek, Ingo, Süße, Marie, Sühs, Kurt W., Urbanek, Christian, Senel, Makbule, Sommer, Claudia, Kuempfel, Tania, Pruess, Harald, Fink, Gereon R., Leypoldt, Frank, Melzer, Nico, and Malter, Michael P.

Published
2023
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12. Seronegative myasthenic crisis: a multicenter analysis

Author

Mergenthaler, Philipp, Stetefeld, Henning R., Dohmen, Christian, Kohler, Siegfried, Schönenberger, Silvia, Bösel, Julian, Gerner, Stefan T., Huttner, Hagen B., Schneider, Hauke, Reichmann, Heinz, Fuhrer, Hannah, Berger, Benjamin, Zinke, Jan, Alberty, Anke, Kleiter, Ingo, Schneider-Gold, Christiane, Roth, Christian, Dunkel, Juliane, Steinbrecher, Andreas, Thieme, Andrea, Lee, De-Hyung, Linker, Ralf A., Angstwurm, Klemens, Meisel, Andreas, and Neumann, Bernhard

Published
2022
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13. Aluminium Chloride instead of Ferric chloride for inducing superior sagittal sinus thrombosis to reduce ferromagnetic artifacts on MRI-imaging in experimental models

Author

Hachenberger, Maaike, primary, Braun, Tobias, additional, Gerner, Stefan T., additional, Suenner, Laura, additional, Schänzer, Anne, additional, Juenemann, Martin, additional, Mueller, Clemens, additional, Wietelmann, Astrid, additional, Stolz, Erwin, additional, Schoenburg, Markus, additional, Tschernatsch, Marlene, additional, Gerriets, Tibo, additional, Huttner, Hagen B., additional, and Yeniguen, Mesut, additional

Published
2024
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16. Seizure Semiology in Antibody-Associated Autoimmune Encephalitis

Author

Kaaden, Tillman, Madlener, Marie, Angstwurm, Klemens, Bien, Christian G., Bogarin, Yuri, Doppler, Kathrin, Finke, Alexander, Gerner, Stefan T., Reimann, Gernot, Häusler, Martin, Handreka, Robert, Hellwig, Kerstin, Kaufmann, Max, Kellinghaus, Christoph, Koertvelyessy, Peter, Kraft, Andrea, Lewerenz, Jan, Menge, Til, Paliantonis, Asterios, von Podewils, Felix, Prüss, Harald, Rauer, Sebastian, Ringelstein, Marius, Rostásy, Kevin, Schirotzek, Ingo, Schwabe, Julia, Sokolowski, Piotr, Suesse, Marie, Sühs, Kurt-Wolfram, Surges, Rainer, Tauber, Simone C., Thaler, Franziska, Bergh, Florian Then, Urbanek, Christian, Wandinger, Klaus-P., Wildemann, Brigitte, Mues, Sigrid, Zettl, Uwe, Leypoldt, Frank, Melzer, Nico, Geis, Christian, Malter, Michael, and Kunze, Albrecht

Published
2022
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18. Comparison of vascular risk profile and clinical outcomes among patients with central (branch) retinal artery occlusion versus amaurosis fugax.

Author

Diel, Norma J., Gerner, Stefan T., Doeppner, Thorsten R., Juenemann, Martin, Maxhuni, Toska, Frühwald, Tobias, Worm, Andre, Alhaj Omar, Omar, Lytvynchuk, Lyubomyr, Struffert, Tobias, Bauer, Pascal, and Huttner, Hagen B.

Subjects
RETINAL artery, RETINAL artery occlusion, BLINDNESS, ISCHEMIC stroke, TREATMENT effectiveness, MONOCULAR vision
Abstract

Background: Retinal artery occlusions lead to sudden, painless vision loss, affecting millions globally. Despite their significance, treatment strategies remain unestablished, contrasting with acute ischemic stroke (AIS), where IVT has proven efficacy. Similar to AIS, retinal artery occlusions demand urgent evaluation and treatment, reflecting the principle "time is retina". Even for patients with transient monocular vision loss, also known as amaurosis fugax (AF), pertinent guidelines meanwhile recommend immediate emergency assessment in a specialized facility. However, data on the clinical benefit and comparability with persistent occlusions are missing. This study aimed to compare the results of a comprehensive stroke-workup among patients with persistent retinal artery occlusions (RAO), including both central retinal (CRAO) and branch retinal artery occlusion (BRAO) and those with AF. Methods: Conducted at the University Hospital Giessen, Germany, this exploratory cross-sectional study enrolled patients with transient or permanent unilateral vision loss of non-arteritic origin. The primary outcome were differences between the two groups RAO and AF with regard to cardiovascular risk profiles and comorbidities, vascular and pharmacological interventions and clinical neurological and ophthalmological outcomes. Secondary outcome was a sub-group analysis of patients receiving IVT. Results: Out of 166 patients assessed, 76 with RAO and 40 with AF met the inclusion criteria. Both groups exhibited comparable age, gender distribution, and cardiovascular risk profiles. Notably, RAO patients did not show significantly more severe vascular comorbidities than AF patients. However, AF patients received vascular interventions more frequently. Pharmacological intervention rates were similar across groups. RAO patients had slightly worse neurological outcomes, and IVT did not yield favorable ophthalmological outcomes within any observed patients. Conclusion: The study found similar vascular burden and risk factors in patients with RAO and AF, with implications for clinical workflows. IVT for RAO may only be effective in very early treatment windows. This emphasizes the need for public awareness and collaborative protocols between ophthalmologists and neurologists to improve outcomes. [ABSTRACT FROM AUTHOR]

Published
2024
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19. POLAR: prediction of prolonged mechanical ventilation in patients with myasthenic crisis.

Author

Heider, Dominik, Stetefeld, Henning, Meisel, Andreas, Bösel, Julian, Artho, Marie, Linker, Ralf, Angstwurm, Klemens, Neumann, Bernhard, Fuchs, Kornelius, Vidal, Amelie, De-Hyung, Lee, Kohler, Siegfried, Mergenthaler, Philipp, Brachaczek, Izabela, Maidhof, Jana, Wenke, Arno, Dohmen, Christian, Schönenberger, Silvia, Gerner, Stefan, and Huttner, Hagen

Subjects
ARTIFICIAL respiration, MYASTHENIA gravis, NEUROLOGICAL intensive care
Abstract

The article introduces a prediction model called POLAR, which is designed to estimate the risk of prolonged mechanical ventilation in patients experiencing myasthenic crisis (MC). MC is a condition associated with myasthenia gravis (MG), an autoimmune disease that affects the neuromuscular junction. The model utilizes 11 selected features, such as age, comorbidities, MG severity, and complications during MC, to predict the likelihood of prolonged mechanical ventilation. The model has been evaluated and found to have an accuracy of 78% in predicting the need for prolonged ventilation. It is available as a web application for physicians to use in clinical practice. The article acknowledges the German Myasthenic Crisis Study Group's contributions and declares no conflicts of interest. [Extracted from the article]

Published
2024
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23. Hematoma Expansion and Clinical Outcomes in Patients With Factor-Xa Inhibitor–Related Atraumatic Intracerebral Hemorrhage Treated Within the ANNEXA-4 Trial Versus Real-World Usual Care

Author

Huttner, Hagen B., Gerner, Stefan T., Kuramatsu, Joji B., Connolly, Stuart J., Beyer-Westendorf, Jan, Demchuk, Andrew M., Middeldorp, Saskia, Zotova, Elena, Altevers, Julia, Andersohn, Frank, Christoph, Mary J., Yue, Patrick, Stross, Leonhard, and Schwab, Stefan

Published
2021
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27. Tracking cell turnover in human brain using 15N-thymidine imaging mass spectrometry

Author

Roeder, Sebastian S., primary, Bonnin, Elisa A., additional, Wu, Ting-Di, additional, Guerquin-Kern, Jean-Luc, additional, Jabari, Samir, additional, Brandner, Sebastian, additional, Eyüpoglu, Ilker Y., additional, Gollwitzer, Stephanie, additional, Hamer, Hajo M., additional, Gerner, Stefan T., additional, Döppner, Thorsten R., additional, Rummel, Christoph, additional, Englund, Elisabet, additional, Heimke-Brinck, Ralph, additional, Borst, Tobias, additional, Daniel, Christoph, additional, Amann, Kerstin, additional, Schlötzer-Schrehardt, Ursula, additional, Tonchev, Anton B., additional, Roessler, Karl, additional, Schwab, Stefan, additional, Bergmann, Olaf, additional, Rizzoli, Silvio O., additional, and Huttner, Hagen B., additional

Published
2023
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29. Tracking cell turnover in human brain using 15N-thymidine imaging mass spectrometry.

Author

Roeder, Sebastian S., Bonnin, Elisa A., Ting-Di Wu, Guerquin-Kern, Jean-Luc, Jabari, Samir, Brandner, Sebastian, Eyüpoglu, Ilker Y., Gollwitzer, Stephanie, Hamer, Hajo M., Gerner, Stefan T., Doeppner, Thorsten R., Rummel, Christoph, Englund, Elisabet, Heimke-Brinck, Ralph, Borst, Tobias, Daniel, Christoph, Amann, Kerstin, Schlötzer-Schrehardt, Ursula, Tonchev, Anton B., and Roessler, Karl

Subjects
MASS spectrometry, NEURAL stem cells, TEMPORAL lobe epilepsy, DENTATE gyrus, BRAIN diseases
Abstract

Microcephaly is often caused by an impairment of the generation of neurons in the brain, a process referred to as neurogenesis. While most neurogenesis in mammals occurs during brain development, it thought to continue to take place through adulthood in selected regions of the mammalian brain, notably the hippocampus. However, the generality of neurogenesis in the adult brain has been controversial. While studies in mice and rats have provided compelling evidence for neurogenesis occurring in the adult rodent hippocampus, the lack of applicability in humans of key methods to demonstrate neurogenesis has led to an intense debate about the existence and, in particular, the magnitude of neurogenesis in the adult human brain. Here, we demonstrate the applicability of a powerful method to address this debate, that is, the in vivo labeling of adult human patients with 15N-thymidine, a non-hazardous form of thymidine, an approach without any clinical harm or ethical concerns. 15N-thymidine incorporation into newly synthesized DNA of specific cells was quantified at the single-cell level with subcellular resolution by Multiple-isotype imaging mass spectrometry (MIMS) of brain tissue resected for medical reasons. Two adult human patients, a glioblastoma patient and a patient with drug-refractory right temporal lobe epilepsy, were infused for 24 h with 15N-thymidine. Detection of 15N-positive leukocyte nuclei in blood samples from these patients confirmed previous findings by others and demonstrated the appropriateness of this approach to search for the generation of new cells in the adult human brain. 15N-positive neural cells were easily identified in the glioblastoma tissue sample, and the range of the 15N signal suggested that cells that underwent S-phase fully or partially during the 24 h in vivo labeling period, as well as cells generated therefrom, were detected. In contrast, within the hippocampus tissue resected from the epilepsy patient, none of the 2,000 dentate gyrus neurons analyzed was positive for 15N-thymidine uptake, consistent with the notion that the rate of neurogenesis in the adult human hippocampus is rather low. Of note, the likelihood of detecting neurogenesis was reduced because of (i) the low number of cells analyzed, (ii) the fact that hippocampal tissue was explored that may have had reduced neurogenesis due to epilepsy, and (iii) the labeling period of 24 h which may have been too short to capture quiescent neural stem cells. Yet, overall, our approach to enrich NeuN-labeled neuronal nuclei by FACS prior to MIMS analysis provides a promising strategy to quantify even low rates of neurogenesis in the adult human hippocampus after in vivo 15N-thymidine infusion. From a general point of view and regarding future perspectives, the in vivo labeling of humans with 15N-thymidine followed by MIMS analysis of brain tissue constitutes a novel approach to study mitotically active cells and their progeny in the brain, and thus allows a broad spectrum of studies of brain physiology and pathology, including microcephaly. [ABSTRACT FROM AUTHOR]

Published
2024
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30. Knockdown of NEAT1 prevents post-stroke lipid droplet agglomeration in microglia by regulating autophagy.

Author

Pan, Yongli, Xin, Wenqiang, Wei, Wei, Tatenhorst, Lars, Graf, Irina, Popa-Wagner, Aurel, Gerner, Stefan T., Huber, Sabine E., Kilic, Ertugrul, Hermann, Dirk M., Bähr, Mathias, Huttner, Hagen B., and Doeppner, Thorsten R.

Abstract

Background: Lipid droplets (LD), lipid-storing organelles containing neutral lipids like glycerolipids and cholesterol, are increasingly accepted as hallmarks of inflammation. The nuclear paraspeckle assembly transcript 1 (NEAT1), a long non-coding RNA with over 200 nucleotides, exerts an indispensable impact on regulating both LD agglomeration and autophagy in multiple neurological disorders. However, knowledge as to how NEAT1 modulates the formation of LD and associated signaling pathways is limited. Methods: In this study, primary microglia were isolated from newborn mice and exposed to oxygen-glucose-deprivation/reoxygenation (OGD/R). To further explore NEAT1-dependent mechanisms, an antisense oligonucleotide (ASO) was adopted to silence NEAT1 under in vitro conditions. Studying NEAT1-dependent interactions with regard to autophagy and LD agglomeration under hypoxic conditions, the inhibitor and activator of autophagy 3-methyladenine (3-MA) and rapamycin (RAPA) were used, respectively. In a preclinical stroke model, mice received intraventricular injections of ASO NEAT1 or control vectors in order to yield NEAT1 knockdown. Analysis of readout parameters included qRT-PCR, immunofluorescence, western blot assays, and behavioral tests. Results: Microglia exposed to OGD/R displayed a temporal pattern of NEAT1 expression, peaking at four hours of hypoxia followed by six hours of reoxygenation. After effectively silencing NEAT1, LD formation and autophagy-related proteins were significantly repressed in hypoxic microglia. Stimulating autophagy in ASO NEAT1 microglia under OGD/R conditions by means of RAPA reversed the downregulation of LD agglomeration and perilipin 2 (PLIN2) expression. On the contrary, application of 3-MA promoted repression of both LD agglomeration and expression of the LD-associated protein PLIN2. Under in vivo conditions, NEAT1 was significantly increased in mice at 24 h post-stroke. Knockdown of NEAT1 significantly alleviated LD agglomeration and inhibited autophagy, resulting in improved cerebral perfusion, reduced brain injury and increased neurological recovery. Conclusion: NEAT1 is a key player of LD agglomeration and autophagy stimulation, and NEAT1 knockdown provides a promising therapeutic value against stroke. [ABSTRACT FROM AUTHOR]

Published
2024
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35. Tracking cell turnover in human brain using 15N-thymidine imaging mass spectrometry.

Author

Roeder, Sebastian S., Bonnin, Elisa A., Ting-Di Wu, Guerquin-Kern, Jean-Luc, Jabari, Samir, Brandner, Sebastian, Eyüpoglu, Ilker Y., Gollwitzer, Stephanie, Hamer, Hajo M., Gerner, Stefan T., Döppner, Thorsten R., Rummel, Christoph, Englund, Elisabet, Heimke-Brinck, Ralph, Borst, Tobias, Daniel, Christoph, Amann, Kerstin, Schlötzer-Schrehardt, Ursula, Tonchev, Anton B., and Roessler, Karl

Subjects
MASS spectrometry, NEURAL stem cells, TEMPORAL lobe epilepsy, DENTATE gyrus, BRAIN diseases
Abstract

Microcephaly is often caused by an impairment of the generation of neurons in the brain, a process referred to as neurogenesis. While most neurogenesis in mammals occurs during brain development, it thought to continue to take place through adulthood in selected regions of the mammalian brain, notably the hippocampus. However, the generality of neurogenesis in the adult brain has been controversial. While studies in mice and rats have provided compelling evidence for neurogenesis occurring in the adult rodent hippocampus, the lack of applicability in humans of key methods to demonstrate neurogenesis has led to an intense debate about the existence and, in particular, the magnitude of neurogenesis in the adult human brain. Here, we demonstrate the applicability of a powerful method to address this debate, that is, the in vivo labeling of adult human patients with 15N-thymidine, a non-hazardous form of thymidine, an approach without any clinical harm or ethical concerns. 15N-thymidine incorporation into newly synthesized DNA of specific cells was quantified at the single-cell level with subcellular resolution by Multiple-isotype imaging mass spectrometry (MIMS) of brain tissue resected for medical reasons. Two adult human patients, a glioblastoma patient and a patient with drug-refractory right temporal lobe epilepsy, were infused for 24 h with 15N-thymidine. Detection of 15N-positive leukocyte nuclei in blood samples from these patients confirmed previous findings by others and demonstrated the appropriateness of this approach to search for the generation of new cells in the adult human brain. 15N-positive neural cells were easily identified in the glioblastoma tissue sample, and the range of the 15N signal suggested that cells that underwent S-phase fully or partially during the 24 h in vivo labeling period, as well as cells generated therefrom, were detected. In contrast, within the hippocampus tissue resected from the epilepsy patient, none of the 2,000 dentate gyrus neurons analyzed was positive for 15N-thymidine uptake, consistent with the notion that the rate of neurogenesis in the adult human hippocampus is rather low. Of note, the likelihood of detecting neurogenesis was reduced because of (i) the low number of cells analyzed, (ii) the fact that hippocampal tissue was explored that may have had reduced neurogenesis due to epilepsy, and (iii) the labeling period of 24 h which may have been too short to capture quiescent neural stem cells. Yet, overall, our approach to enrich NeuN-labeled neuronal nuclei by FACS prior to MIMS analysis provides a promising strategy to quantify even low rates of neurogenesis in the adult human hippocampus after in vivo15N-thymidine infusion. From a general point of view and regarding future perspectives, the in vivo labeling of humans with 15N-thymidine followed by MIMS analysis of brain tissue constitutes a novel approach to study mitotically active cells and their progeny in the brain, and thus allows a broad spectrum of studies of brain physiology and pathology, including microcephaly. [ABSTRACT FROM AUTHOR]

Published
2023
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36. Myasthenic crisis demanding mechanical ventilation: A multicenter analysis of 250 cases

Author

Neumann, Bernhard, Angstwurm, Klemens, Mergenthaler, Philipp, Kohler, Siegfried, Schönenberger, Silvia, Bösel, Julian, Neumann, Ursula, Vidal, Amelie, Huttner, Hagen B., Gerner, Stefan T., Thieme, Andrea, Steinbrecher, Andreas, Dunkel, Juliane, Roth, Christian, Schneider, Haucke, Schimmel, Eik, Fuhrer, Hannah, Fahrendorf, Christine, Alberty, Anke, Zinke, Jan, Meisel, Andreas, Dohmen, Christian, and Stetefeld, Henning R.

Published
2020
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39. Characteristics in Non–Vitamin K Antagonist Oral Anticoagulant–Related Intracerebral Hemorrhage

Author

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

Published
2019
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41. Cerebrospinal fluid in Borna disease virus 1 (BoDV-1) encephalitis

Author

Neumann, Bernhard, primary, Hierl, Andreas, additional, Wunderlich, Silke, additional, Meier, Helen, additional, Bauer, Christina, additional, Gerner, Stefan T., additional, Rieder, Georg, additional, Geis, Tobias, additional, Kunkel, Jürgen, additional, Bauswein, Markus, additional, Niller, Hans Helmut, additional, Schmidt, Barbara, additional, Rubbensroth, Dennis, additional, Beer, Martin, additional, Linker, Ralf A., additional, Jantsch, Jonathan, additional, and Angstwurm, Klemens, additional

Published
2023
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43. Preconditioned extracellular vesicles from hypoxic microglia reduce poststroke AQP4 depolarization, disturbed cerebrospinal fluid flow, astrogliosis, and neuroinflammation

Author

Xin, Wenqiang, primary, Pan, Yongli, additional, Wei, Wei, additional, Tatenhorst, Lars, additional, Graf, Irina, additional, Popa-Wagner, Aurel, additional, Gerner, Stefan T, additional, Huber, Sabine, additional, Kilic, Ertugrul, additional, Hermann, Dirk M, additional, Bähr, Mathias, additional, Huttner, Hagen B, additional, and Doeppner, Thorsten R, additional

Published
2023
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45. Neuroprotective strategies for ischemic stroke—Future perspectives

Author

Haupt, Matteo, Gerner, Stefan T., Bähr, Mathias, and Doeppner, Thorsten R.

Subjects
Stroke, Cerebral Ischemia, Extracellular Vesicle, Stem Cells, Microbiota–Gut–Brain Axis, Neuroprotection
Abstract

Ischemic stroke is the main cause of death and the most common cause of acquired physical disability worldwide. Recent demographic changes increase the relevance of stroke and its sequelae. The acute treatment for stroke is restricted to causative recanalization and restoration of cerebral blood flow, including both intravenous thrombolysis and mechanical thrombectomy. Still, only a limited number of patients are eligible for these time-sensitive treatments. Hence, new neuroprotective approaches are urgently needed. Neuroprotection is thus defined as an intervention resulting in the preservation, recovery, and/or regeneration of the nervous system by interfering with the ischemic-triggered stroke cascade. Despite numerous preclinical studies generating promising data for several neuroprotective agents, successful bench-to-bedside translations are still lacking. The present study provides an overview of current approaches in the research field of neuroprotective stroke treatment. Aside from “traditional” neuroprotective drugs focusing on inflammation, cell death, and excitotoxicity, stem-cell-based treatment methods are also considered. Furthermore, an overview of a prospective neuroprotective method using extracellular vesicles that are secreted from various stem cell sources, including neural stem cells and bone marrow stem cells, is also given. The review concludes with a short discussion on the microbiota–gut–brain axis that may serve as a potential target for future neuroprotective therapies.

Published
2023

46. 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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48. Management and prognostic markers in patients with autoimmune encephalitis requiring ICU treatment

Author

Schubert, Julia, Brämer, Dirk, Huttner, Hagen B., Gerner, Stefan T., Fuhrer, Hannah, Melzer, Nico, Dik, Andre, Prüss, Harald, Ly, Lam-Than, Fuchs, Kornelius, Leypoldt, Frank, Nissen, Gunnar, Schirotzek, Ingo, Dohmen, Christian, Bösel, Julian, Lewerenz, Jan, Thaler, Franziska, Kraft, Andrea, Juranek, Aleksandra, Ringelstein, Marius, Sühs, Kurt-Wolfram, Urbanek, Christian, Scherag, André, Geis, Christian, Witte, Otto W., and Günther, Albrecht

Published
2019
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50. Can flat-detector CT after successful endovascular treatment predict long-term outcome in patients with large vessel occlusion? An Alberta Stroke Programme Early CT Score–based study

Author

Knott, Michael, primary, Hoelter, Philip, additional, Hock, Stefan, additional, Mühlen, Iris, additional, Gerner, Stefan T., additional, Sprügel, Maximilian I., additional, Huttner, Hagen B., additional, Schwab, Stefan, additional, Engelhorn, Tobias, additional, and Doerfler, Arnd, additional

Published
2022
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