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4. New Mechanistic Insights, Novel Treatment Paradigms, and Clinical Progress in Cerebrovascular Diseases.

Author

Boltze, Johannes, Aronowski, Jaroslaw A, Badaut, Jerome, Buckwalter, Marion S, Caleo, Mateo, Chopp, Michael, Dave, Kunjan R, Didwischus, Nadine, Dijkhuizen, Rick M, Doeppner, Thorsten R, Dreier, Jens P, Fouad, Karim, Gelderblom, Mathias, Gertz, Karen, Golubczyk, Dominika, Gregson, Barbara A, Hamel, Edith, Hanley, Daniel F, Härtig, Wolfgang, Hummel, Friedhelm C, Ikhsan, Maulana, Janowski, Miroslaw, Jolkkonen, Jukka, Karuppagounder, Saravanan S, Keep, Richard F, Koerte, Inga K, Kokaia, Zaal, Li, Peiying, Liu, Fudong, Lizasoain, Ignacio, Ludewig, Peter, Metz, Gerlinde AS, Montagne, Axel, Obenaus, Andre, Palumbo, Alex, Pearl, Monica, Perez-Pinzon, Miguel, Planas, Anna M, Plesnila, Nikolaus, Raval, Ami P, Rueger, Maria A, Sansing, Lauren H, Sohrabji, Farida, Stagg, Charlotte J, Stetler, R Anne, Stowe, Ann M, Sun, Dandan, Taguchi, Akihiko, Tanter, Mickael, Vay, Sabine U, Vemuganti, Raghu, Vivien, Denis, Walczak, Piotr, Wang, Jian, Xiong, Ye, and Zille, Marietta

Subjects
cell therapies, dementia, experimental therapy, hemorrhage, neuroprotection, neurorehabilitation, stroke, translational research, Biochemistry and Cell Biology, Neurosciences, Cognitive Sciences
Abstract

The past decade has brought tremendous progress in diagnostic and therapeutic options for cerebrovascular diseases as exemplified by the advent of thrombectomy in ischemic stroke, benefitting a steeply increasing number of stroke patients and potentially paving the way for a renaissance of neuroprotectants. Progress in basic science has been equally impressive. Based on a deeper understanding of pathomechanisms underlying cerebrovascular diseases, new therapeutic targets have been identified and novel treatment strategies such as pre- and post-conditioning methods were developed. Moreover, translationally relevant aspects are increasingly recognized in basic science studies, which is believed to increase their predictive value and the relevance of obtained findings for clinical application.This review reports key results from some of the most remarkable and encouraging achievements in neurovascular research that have been reported at the 10th International Symposium on Neuroprotection and Neurorepair. Basic science topics discussed herein focus on aspects such as neuroinflammation, extracellular vesicles, and the role of sex and age on stroke recovery. Translational reports highlighted endovascular techniques and targeted delivery methods, neurorehabilitation, advanced functional testing approaches for experimental studies, pre-and post-conditioning approaches as well as novel imaging and treatment strategies. Beyond ischemic stroke, particular emphasis was given on activities in the fields of traumatic brain injury and cerebral hemorrhage in which promising preclinical and clinical results have been reported. Although the number of neutral outcomes in clinical trials is still remarkably high when targeting cerebrovascular diseases, we begin to evidence stepwise but continuous progress towards novel treatment options. Advances in preclinical and translational research as reported herein are believed to have formed a solid foundation for this progress.

Published
2021

9. CNS Myelin Wrapping Is Driven by Actin Disassembly

Author

Zuchero, J Bradley, Fu, Meng-meng, Sloan, Steven A, Ibrahim, Adiljan, Olson, Andrew, Zaremba, Anita, Dugas, Jason C, Wienbar, Sophia, Caprariello, Andrew V, Kantor, Christopher, Leonoudakis, Dmitri, Lariosa-Willingham, Karen, Kronenberg, Golo, Gertz, Karen, Soderling, Scott H, Miller, Robert H, and Barres, Ben A

Subjects
Biochemistry and Cell Biology, Biological Sciences, Neurosciences, Neurodegenerative, Brain Disorders, Autoimmune Disease, Multiple Sclerosis, 1.1 Normal biological development and functioning, Underpinning research, Neurological, Actin Cytoskeleton, Actin-Related Protein 2-3 Complex, Actins, Animals, Axons, Cell Membrane, Cell Movement, Cells, Cultured, Central Nervous System, Cofilin 1, Gelsolin, Mice, Mice, Inbred C57BL, Mice, Knockout, Myelin Basic Protein, Myelin Sheath, Oligodendroglia, Optic Nerve, RNA Interference, RNA, Small Interfering, Rats, Rats, Sprague-Dawley, Medical and Health Sciences, Developmental Biology, Biochemistry and cell biology
Abstract

Myelin is essential in vertebrates for the rapid propagation of action potentials, but the molecular mechanisms driving its formation remain largely unknown. Here we show that the initial stage of process extension and axon ensheathment by oligodendrocytes requires dynamic actin filament assembly by the Arp2/3 complex. Unexpectedly, subsequent myelin wrapping coincides with the upregulation of actin disassembly proteins and rapid disassembly of the oligodendrocyte actin cytoskeleton and does not require Arp2/3. Inducing loss of actin filaments drives oligodendrocyte membrane spreading and myelin wrapping in vivo, and the actin disassembly factor gelsolin is required for normal wrapping. We show that myelin basic protein, a protein essential for CNS myelin wrapping whose role has been unclear, is required for actin disassembly, and its loss phenocopies loss of actin disassembly proteins. Together, these findings provide insight into the molecular mechanism of myelin wrapping and identify it as an actin-independent form of mammalian cell motility.

Published
2015

10. The atypical antidepressant tianeptine confers neuroprotection against oxygen–glucose deprivation.

Author

Ersoy, Burcu, Herzog, Marie-Louise, Pan, Wen, Schilling, Simone, Endres, Matthias, Göttert, Ria, Kronenberg, Golo D., and Gertz, Karen

Subjects
SERUM-free culture media, ANTIDEPRESSANTS, CELL death, GENETIC transcription, CELL survival
Abstract

Proregenerative and neuroprotective effects of antidepressants are an important topic of inquiry in neuropsychiatric research. Oxygen–glucose deprivation (OGD) mimics key aspects of ischemic injury in vitro. Here, we studied the effects of 24-h pretreatment with serotonin (5-HT), citalopram (CIT), fluoxetine (FLU), and tianeptine (TIA) on primary mouse cortical neurons subjected to transient OGD. 5-HT (50 μM) significantly enhanced neuron viability as measured by MTT assay and reduced cell death and LDH release. CIT (10 μM) and FLU (1 μM) did not increase the effects of 5-HT and neither antidepressant conferred neuroprotection in the absence of supplemental 5-HT in serum-free cell culture medium. By contrast, pre-treatment with TIA (10 μM) resulted in robust neuroprotection, even in the absence of 5-HT. Furthermore, TIA inhibited mRNA transcription of candidate genes related to cell death and hypoxia and attenuated lipid peroxidation, a hallmark of neuronal injury. Finally, deep RNA sequencing of primary neurons subjected to OGD demonstrated that OGD induces many pathways relating to cell survival, the inflammation-immune response, synaptic dysregulation and apoptosis, and that TIA pretreatment counteracted these effects of OGD. In conclusion, this study highlights the comparative strength of the 5-HT independent neuroprotective effects of TIA and identifies the molecular pathways involved. [ABSTRACT FROM AUTHOR]

Published
2024
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32. New Mechanistic Insights, Novel Treatment Paradigms, and Clinical Progress in Cerebrovascular Diseases

Author

German Research Foundation, International Society for Cerebral Blood Flow and Metabolism, Boltze, Johannes, Aronowski, Jaroslaw A., Badaut, Jerome, Buckwalter, Marion S., Caleo, Mateo, Chopp, Michael, Dave, Kunjan R., Didwischus, Nadine, Dijkhuizen, Rick M., Doeppner, Thorsten R., Dreier, Jens P., Fouad, Karim, Gelderblom, Mathias, Gertz, Karen, Golubczyk, Dominika, Gregson, Barbara A., Hamel, Edith, Hanley, Daniel F., Härtig, Wolfgang, Hummel, Friedhelm C., Ikhsan, Maulana, Janowski, Miroslaw, Jolkkonen, Jukka, Karuppagounder, Saravanan S., Keep, Richard F., Koerte, Inga K., Kokaia, Zaal, Li, Peiying, Liu, Fudong, Lizasoain, Ignacio, Ludewig, Peter, Metz, Gerlinde A. S., Montagne, Axel, Obenaus, Andre, Palumbo, Alex, Pearl, Monica, Perez-Pinzon, Miguel, Planas, Anna M., Plesnila, Nikolaus, Raval, Ami P., Rueger, Maria A., Sansing, Lauren H., Sohrabji, Farida, Stagg, Charlotte J., Stetler, R. Anne, Stowe, Ann M., Sun, Dandan, Taguchi, Akihiko, Tanter, Mickael, Vay,Sabine U., Vemuganti, Raghu, Vivien, Denis, Walczak, Piotr, Wang, Jian, Xiong, Ye, Zille, Marietta, German Research Foundation, International Society for Cerebral Blood Flow and Metabolism, Boltze, Johannes, Aronowski, Jaroslaw A., Badaut, Jerome, Buckwalter, Marion S., Caleo, Mateo, Chopp, Michael, Dave, Kunjan R., Didwischus, Nadine, Dijkhuizen, Rick M., Doeppner, Thorsten R., Dreier, Jens P., Fouad, Karim, Gelderblom, Mathias, Gertz, Karen, Golubczyk, Dominika, Gregson, Barbara A., Hamel, Edith, Hanley, Daniel F., Härtig, Wolfgang, Hummel, Friedhelm C., Ikhsan, Maulana, Janowski, Miroslaw, Jolkkonen, Jukka, Karuppagounder, Saravanan S., Keep, Richard F., Koerte, Inga K., Kokaia, Zaal, Li, Peiying, Liu, Fudong, Lizasoain, Ignacio, Ludewig, Peter, Metz, Gerlinde A. S., Montagne, Axel, Obenaus, Andre, Palumbo, Alex, Pearl, Monica, Perez-Pinzon, Miguel, Planas, Anna M., Plesnila, Nikolaus, Raval, Ami P., Rueger, Maria A., Sansing, Lauren H., Sohrabji, Farida, Stagg, Charlotte J., Stetler, R. Anne, Stowe, Ann M., Sun, Dandan, Taguchi, Akihiko, Tanter, Mickael, Vay,Sabine U., Vemuganti, Raghu, Vivien, Denis, Walczak, Piotr, Wang, Jian, Xiong, Ye, and Zille, Marietta

Abstract

The past decade has brought tremendous progress in diagnostic and therapeutic options for cerebrovascular diseases as exemplified by the advent of thrombectomy in ischemic stroke, benefitting a steeply increasing number of stroke patients and potentially paving the way for a renaissance of neuroprotectants. Progress in basic science has been equally impressive. Based on a deeper understanding of pathomechanisms underlying cerebrovascular diseases, new therapeutic targets have been identified and novel treatment strategies such as pre- and post-conditioning methods were developed. Moreover, translationally relevant aspects are increasingly recognized in basic science studies, which is believed to increase their predictive value and the relevance of obtained findings for clinical application.This review reports key results from some of the most remarkable and encouraging achievements in neurovascular research that have been reported at the 10th International Symposium on Neuroprotection and Neurorepair. Basic science topics discussed herein focus on aspects such as neuroinflammation, extracellular vesicles, and the role of sex and age on stroke recovery. Translational reports highlighted endovascular techniques and targeted delivery methods, neurorehabilitation, advanced functional testing approaches for experimental studies, pre-and post-conditioning approaches as well as novel imaging and treatment strategies. Beyond ischemic stroke, particular emphasis was given on activities in the fields of traumatic brain injury and cerebral hemorrhage in which promising preclinical and clinical results have been reported. Although the number of neutral outcomes in clinical trials is still remarkably high when targeting cerebrovascular diseases, we begin to evidence stepwise but continuous progress towards novel treatment options. Advances in preclinical and translational research as reported herein are believed to have formed a solid foundation for this progress.

Published
2021

33. New Mechanistic Insights, Novel Treatment Paradigms, and Clinical Progress in Cerebrovascular Diseases

Author

In Vivo NMR ISI, Brain, Circulatory Health, Boltze, Johannes, Aronowski, Jaroslaw A., Badaut, Jerome, Buckwalter, Marion S., Caleo, Mateo, Chopp, Michael, Dave, Kunjan R., Didwischus, Nadine, Dijkhuizen, Rick M., Doeppner, Thorsten R., Dreier, Jens P., Fouad, Karim, Gelderblom, Mathias, Gertz, Karen, Golubczyk, Dominika, Gregson, Barbara A., Hamel, Edith, Hanley, Daniel F., Härtig, Wolfgang, Hummel, Friedhelm C., Ikhsan, Maulana, Janowski, Miroslaw, Jolkkonen, Jukka, Karuppagounder, Saravanan S., Keep, Richard F., Koerte, Inga K., Kokaia, Zaal, Li, Peiying, Liu, Fudong, Lizasoain, Ignacio, Ludewig, Peter, Metz, Gerlinde A.S., Montagne, Axel, Obenaus, Andre, Palumbo, Alex, Pearl, Monica, Perez-Pinzon, Miguel, Planas, Anna M., Plesnila, Nikolaus, Raval, Ami P., Rueger, Maria A., Sansing, Lauren H., Sohrabji, Farida, Stagg, Charlotte J., Stetler, R. Anne, Stowe, Ann M., Sun, Dandan, Taguchi, Akihiko, Tanter, Mickael, Vay, Sabine U., Vemuganti, Raghu, Vivien, Denis, Walczak, Piotr, Wang, Jian, Xiong, Ye, Zille, Marietta, In Vivo NMR ISI, Brain, Circulatory Health, Boltze, Johannes, Aronowski, Jaroslaw A., Badaut, Jerome, Buckwalter, Marion S., Caleo, Mateo, Chopp, Michael, Dave, Kunjan R., Didwischus, Nadine, Dijkhuizen, Rick M., Doeppner, Thorsten R., Dreier, Jens P., Fouad, Karim, Gelderblom, Mathias, Gertz, Karen, Golubczyk, Dominika, Gregson, Barbara A., Hamel, Edith, Hanley, Daniel F., Härtig, Wolfgang, Hummel, Friedhelm C., Ikhsan, Maulana, Janowski, Miroslaw, Jolkkonen, Jukka, Karuppagounder, Saravanan S., Keep, Richard F., Koerte, Inga K., Kokaia, Zaal, Li, Peiying, Liu, Fudong, Lizasoain, Ignacio, Ludewig, Peter, Metz, Gerlinde A.S., Montagne, Axel, Obenaus, Andre, Palumbo, Alex, Pearl, Monica, Perez-Pinzon, Miguel, Planas, Anna M., Plesnila, Nikolaus, Raval, Ami P., Rueger, Maria A., Sansing, Lauren H., Sohrabji, Farida, Stagg, Charlotte J., Stetler, R. Anne, Stowe, Ann M., Sun, Dandan, Taguchi, Akihiko, Tanter, Mickael, Vay, Sabine U., Vemuganti, Raghu, Vivien, Denis, Walczak, Piotr, Wang, Jian, Xiong, Ye, and Zille, Marietta

Published
2021

38. Protein kinase CK2 links extracellular growth factor signaling with the control of [p27.sup.Kip1] stability in the heart

Author

Hauck, Ludger, Harms, Christoph, An, Junfeng, Rohne, Jens, Gertz, Karen, Dietz, Rainer, Endres, Matthias, and von Harsdorf, Rudiger

Abstract

[p27.sup.Kip1] (p27) blocks cell proliferation through the inhibition of cyclin-dependent kinase-2 (Cdk2). Despite its robust expression in the heart, little is known about both the function and regulation of p27 in this and other nonproliferative tissues, in which the expression of its main target, cyclin E-Cdk2, is known to be very low. Here we show that angiotensin II, a major cardiac growth factor, induces the proteasomal degradation of p27 through protein kinase CK2-[alpha]'-dependent phosphorylation. Conversely, unphosphorylated p27 potently inhibits CK2-[alpha]'. Thus, the p27-CK2-[alpha] interaction is regulated by hypertrophic signaling events and represents a regulatory feedback loop in differentiated cardiomyocytes analogous to, but distinct from, the feedback loop arising from the interaction of p27 with Cdk2 that controls cell proliferation. Our data show that extracellular growth factor signaling regulates p27 stability in postmitotic cells, and that inactivation of p27 by CK2-[alpha] is crucial for agonist- and stress-induced cardiac hypertrophic growth., The tumor suppressor p27 is a potent inhibitor of cell growth and divisions (1). Antiproliferative signals lead to accumulation and stabilization of p27, which can then inhibit Cdk2 and cause [...]

Published
2008

40. New Mechanistic Insights, Novel Treatment Paradigms, and Clinical Progress in Cerebrovascular Diseases

Author

Boltze, Johannes, primary, Aronowski, Jaroslaw A., additional, Badaut, Jerome, additional, Buckwalter, Marion S., additional, Caleo, Mateo, additional, Chopp, Michael, additional, Dave, Kunjan R., additional, Didwischus, Nadine, additional, Dijkhuizen, Rick M., additional, Doeppner, Thorsten R., additional, Dreier, Jens P., additional, Fouad, Karim, additional, Gelderblom, Mathias, additional, Gertz, Karen, additional, Golubczyk, Dominika, additional, Gregson, Barbara A., additional, Hamel, Edith, additional, Hanley, Daniel F., additional, Härtig, Wolfgang, additional, Hummel, Friedhelm C., additional, Ikhsan, Maulana, additional, Janowski, Miroslaw, additional, Jolkkonen, Jukka, additional, Karuppagounder, Saravanan S., additional, Keep, Richard F., additional, Koerte, Inga K., additional, Kokaia, Zaal, additional, Li, Peiying, additional, Liu, Fudong, additional, Lizasoain, Ignacio, additional, Ludewig, Peter, additional, Metz, Gerlinde A. S., additional, Montagne, Axel, additional, Obenaus, Andre, additional, Palumbo, Alex, additional, Pearl, Monica, additional, Perez-Pinzon, Miguel, additional, Planas, Anna M., additional, Plesnila, Nikolaus, additional, Raval, Ami P., additional, Rueger, Maria A., additional, Sansing, Lauren H., additional, Sohrabji, Farida, additional, Stagg, Charlotte J., additional, Stetler, R. Anne, additional, Stowe, Ann M., additional, Sun, Dandan, additional, Taguchi, Akihiko, additional, Tanter, Mickael, additional, Vay, Sabine U., additional, Vemuganti, Raghu, additional, Vivien, Denis, additional, Walczak, Piotr, additional, Wang, Jian, additional, Xiong, Ye, additional, and Zille, Marietta, additional

Published
2021
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