Division of Pharmacology and Toxicology

Cerebrovascular Pharmacology

Malena Brenek

Mission statement

Cerebrovascular diseases, such as stroke, brain hemorrhage, and dementia, are the leading causes of death and disability and present an enormous socioeconomic burden worldwide. Current estimates predict that their prevalence will further increase as 25 % of the population will be over 65 years of age by 2030.

Current explicative models of these diseases account for signs and symptoms that are already present in affected patients. However, we now know that these diseases are life-spanning processes that start silently at least 20 to 30 years before symptoms are perceived. It is therefore difficult to identify real cause from mere consequences.

Our research group aims to identify the underlying etiology of cerebrovascular disease and brain aging in addition to studying its pathophysiology in order to identify novel targets and to develop innovative therapies for prevention, cytoprotection, regeneration, and recovery of motor and cognitive function that are limited in patients suffering from these devastating diseases.

Our current projects are:

  1. Unraveling the gut-brain axis in cerebrovascular diseases: Exploring soluble fiber-rich diet to mitigate the detrimental effects of hypertension and hemorrhagic stroke
     
  2. Identifying the mechanisms underlying the protective effect of short-chain fatty acids
     
  3. Understanding the mechanisms of cell death after subretinal hemorrhage
     
  4. Characterizing aging of the blood-brain barrier
     
  5. Identifying bioactive compounds for healthy brain aging

Funding

  1. 2026-2030: University of Vienna Research Platform: Non-Enzymatic Protein Modifications in Neurodegeneration, in collaboration with Prof. Dr. Christian Becker (Faculty of Chemistry), Prof. Dr. Christoph Rademacher (Faculty of Life Sciences), Prof. Dr. Sascha Martens (Max Perutz Labs)
  1. 2025-2027: Interdisciplinary Research Networks grant of the Faculty of Life Sciences, University of Vienna, in collaboration with Dr. Felix Sternberg (Dept. of Nutritional Sciences): Targeting Senescence - Investigating the Protective Effects of Short- and Medium-Chain Fatty Acids on Cardiac and Blood-Brain Barrier Aging. 
  1. 2025-2026: IBRO Collaborative Research Grant: NeuroGuard - Targeted intervention at the blood-brain barrier interface for age-related neurovascular resilience. In collaboration with Assoc.-Prof. Dr. Kotaro Yoshioka, Tokyo Medical and Dental University, Japan 
  1. 2025-2026: Hochschuljubiläumsfonds der Stadt Wien (Project number: H-506512/2024): Unraveling the gut-brain axis: Exploring soluble fiber-rich diet to mitigate the detrimental effects of high blood pressure on the brain 
  1. 2024-2027: Austrian Academy of Sciences (ÖAW Project number: 27097): Identification of the metabolites associated with a dietary intervention that protect against hypertension-induced cerebrovascular injury 
  1. 2023: Hochschuljubiläumsfonds der Stadt Wien (Project number: H-902282/2022): Unraveling mechanisms of axonal degeneration in intracerebral hemorrhage 
  1. 2018-2020: Fraunhofer Society MEF EnTireAxon – Test system to systematically investigate axons
  1. 2018-2019: Interstellar Initiative of the Japan Agency for Medical Research and Development and the New York Academy of Sciences 
  1. 2018-2019: BMBF MERCEDES – Multimodal Enhancement of Nerve Tissue Regeneration using Cellular Approaches for Degenerative Nervous System diseases 
  1. 2018-2019: BMBF NEPTUN – German-Mexican Roundtable Exploring New Etiological Paths Towards Neurodegeneration

Publications

2022

Mortimer, KRH, Vernon-Browne, H, Zille, M, Didwischus, N & Boltze, J 2022, 'Potential effects of commonly applied drugs on neural stem cell proliferation and viability: A hypothesis-generating systematic review and meta-analysis', Frontiers in molecular neuroscience, vol. 15, 975697. https://doi.org/10.3389/fnmol.2022.975697

Gutiérrez-Ospina, G, Perez-Cruz, C, Zenaro, E & Zille, M 2022, 'Editorial: Neurodegenerative Diseases: Looking Beyond the Boundaries of the Brain', Frontiers in Neuroscience, vol. 16, 929786. https://doi.org/10.3389/fnins.2022.929786

Zille, M, Oses-Prieto, JA, Savage, SR, Karuppagounder, SS, Chen, Y, Kumar, A, Morris, JH, Scheidt, KA, Burlingame, AL & Ratan, RR 2022, 'Hemin-Induced Death Models Hemorrhagic Stroke and Is a Variant of Classical Neuronal Ferroptosis', The Journal of Neuroscience, vol. 42, no. 10, pp. 2065-2079. https://doi.org/10.1523/JNEUROSCI.0923-20.2021

Zille, M, Plesnila, N & Boltze, J 2022, 'Pharmacologically targeting inflammation and improving cerebrospinal fluid circulation improves outcome after subarachnoid haemorrhage', EBioMedicine, vol. 77, 103937. https://doi.org/10.1016/j.ebiom.2022.103937

Maluje, Y & Zille, M 2022, Integrating phase-contrast and fluorescence microscopy data for the analysis of axonal degeneration in a model of intracerebral hemorrhage using deep learning. in Student Conference Proceedings 2022. ‎ Infinite Science Publishing, Lübeck.

Zille, M, Farr, TD, Keep, RF, Römer, C, Xi, G & Boltze, J 2022, 'Novel targets, treatments, and advanced models for intracerebral haemorrhage', EBioMedicine, vol. 76, 103880. https://doi.org/10.1016/j.ebiom.2022.103880

2021

Winek, K, Zanatta, DC & Zille, M 2021, 'Brain–body communication in stroke: Mens sana in corpore sano', Neuroforum, vol. 28, no. 1, pp. 31-39. https://doi.org/10.1515/nf-2021-0030

Wenzel, J, Lampe, J, Müller-Fielitz, H, Schuster, R, Zille, M, Müller, K, Krohn, M, Körbelin, J, Zhang, L, Özorhan, Ü, Neve, V, Wagner, JUG, Bojkova, D, Shumliakivska, M, Jiang, Y, Fähnrich, A, Ott, F, Sencio, V, Robil, C, Pfefferle, S, Sauve, F, Coêlho, CFF, Franz, J, Spiecker, F, Lembrich, B, Binder, S, Feller, N, König, P, Busch, H, Collin, L, Villaseñor, R, Jöhren, O, Altmeppen, HC, Pasparakis, M, Dimmeler, S, Cinatl, J, Püschel, K, Zelic, M, Ofengeim, D, Stadelmann, C, Trottein, F, Nogueiras, R, Hilgenfeld, R, Glatzel, M, Prevot, V & Schwaninger, M 2021, 'The SARS-CoV-2 main protease Mpro causes microvascular brain pathology by cleaving NEMO in brain endothelial cells', Nature Neuroscience, vol. 24, no. 11, pp. 1522–1533. https://doi.org/10.1038/s41593-021-00926-1

Dörschmann, P, Apitz, S, Hellige, I, Neupane, S, Alban, S, Kopplin, G, Ptak, S, Fretté, X, Roider, J, Zille, M & Klettner, A 2021, 'Evaluation of the Effects of Fucoidans from Fucus Species and Laminaria hyperborea against Oxidative Stress and Iron-Dependent Cell Death', Marine Drugs, vol. 19, no. 10, 557. https://doi.org/10.3390/md19100557

Palumbo, A, Gruening, P, Landt, SK, Heckmann, LE, Bartram, L, Pabst, A, Flory, C, Ikhsan, M, Pietsch, S, Schulz, R, Kren, C, Koop, N, Boltze, J, Mamlouk, AM & Zille, M 2021, 'Deep Learning to Decipher the Progression and Morphology of Axonal Degeneration', Cells, vol. 10, no. 10, 2539. https://doi.org/10.3390/cells10102539

Krueger, K, Boehme, E, Klettner, AK & Zille, M 2021, 'The potential of marine resources for retinal diseases: a systematic review of the molecular mechanisms', Critical Reviews in Food Science and Nutrition, vol. 62, no. 27, pp. 7518-7560. https://doi.org/10.1080/10408398.2021.1915242

Boltze, J, Aronowski, JA, Badaut, J, Buckwalter, MS, Caleo, M, Chopp, M, Dave, KR, Didwischus, N, Dijkhuizen, RM, Doeppner, TR, Dreier, JP, Fouad, K, Gelderblom, M, Gertz, K, Golubczyk, D, Gregson, BA, Hamel, E, Hanley, DF, Haertig, W, Hummel, FC, Ikhsan, M, Janowski, M, Jolkkonen, J, Karuppagounder, SS, Keep, RF, Koerte, IK, Kokaia, Z, Li, P, Liu, F, Lizasoain, I, Ludewig, P, Metz, GAS, Montagne, A, Obenaus, A, Palumbo, A, Pearl, M, Perez-Pinzon, M, Planas, AM, Plesnila, N, Raval, AP, Rueger, MA, Sansing, LH, Sohrabji, F, Stagg, CJ, Stetler, RA, Stowe, AM, Sun, D, Taguchi, A, Tanter, M, Vay, SU, Vemuganti, R, Vivien, D, Walczak, P, Wang, J, Xiong, Y & Zille, M 2021, 'New Mechanistic Insights, Novel Treatment Paradigms, and Clinical Progress in Cerebrovascular Diseases', Frontiers in Aging Neuroscience, vol. 13, 623751. https://doi.org/10.3389/FNAGI.2021.623751

Auer, N & Zille, M 2021, Detection of Axonal Degeneration in Microscopic Image Time Series using a Deep Learning Approach. in TM Buzug (ed.), Student Conference Proceedings 2021 : 10th Conference on Medical Engineering Science, 6th Conference on Medical Informatics, 4th Conference on Biomedical Engineering, 3rd Conference on Auditory Technology, 1st Conference on Biophysics, 1st Conference on Robotics and Autonomous Systems : Lübeck, March 10-12, 2021. ‎ Infinite Science Publishing, Lübeck, pp. 341-344.

Grüning, P, Palumbo, A, Landt, SK, Heckmann, L, Brackhagen, L, Zille, M & Mamlouk, AM 2021, Robust and Markerfree in vitro Axon Segmentation with CNNs. in J Ye, MJ O’Grady, G Civitarese & K Yordanova (eds), Wireless Mobile Communication and Healthcare - 9th EAI International Conference, MobiHealth 2020, Proceedings. 1. edn, Springer International Publishing, Cham, Lecture Notes of the Institute for Computer Sciences Social Informatics and Telecommunications Engineering, vol. 362, pp. 274-284. https://doi.org/10.1007/978-3-030-70569-5_17

2020

Riabinska, A, Zille, M, Terzi, MY, Cordell, R, Nieminen-Kelhä, M, Klohs, J & Piña, AL 2020, 'Correction to: Pigment Epithelium-Derived Factor Improves Paracellular Blood–Brain Barrier Integrity in the Normal and Ischemic Mouse Brain', Cellular and Molecular Neurobiology, vol. 40, no. 5, pp. 765-766. https://doi.org/10.1007/s10571-020-00872-9

Riabinska, A, Zille, M, Terzi, MY, Cordell, R, Nieminen-Kelhä, M, Klohs, J & Piña, AL 2020, 'Pigment Epithelium-Derived Factor Improves Paracellular Blood–Brain Barrier Integrity in the Normal and Ischemic Mouse Brain', Cellular and Molecular Neurobiology, vol. 40, no. 5, pp. 751-764. https://doi.org/10.1007/s10571-019-00770-9

Menon, NK, Palumbo, A, Gruening, P, Landt, SK, Heckmann, LE, Bartram, L, Mamlouk, AM & Zille, M 2020, Segmentation of fluorescently labelled axons in a model of brain hemorrhage-induced axonal degeneration using convolutional neural networks. in TM Buzug (ed.), Student Conference Proceedings 2020: 9th Conference on Medical Engineering Science, 5th Conference on Medical Informatics, 3rd Conference on Biomedical Engineering, 2nd Conference on Auditory Technology : Lübeck, March 3-5, 2020. ‎ Infinite Science Publishing, Lübeck, pp. 229-232.

2019

Boltze, J, Ferrara, F, Hainsworth, AH, Bridges, LR, Zille, M, Lobsien, D, Barthel, H, McLeod, DD, Gräßer, F, Pietsch, S, Schatzl, A-K, Dreyer, AY & Nitzsche, B 2019, 'Lesional and perilesional tissue characterization by automated image processing in a novel gyrencephalic animal model of peracute intracerebral hemorrhage', Journal of Cerebral Blood Flow & Metabolism, vol. 39, no. 12, pp. 2521-2535. https://doi.org/10.1177/0271678X18802119

Zille, M, Ikhsan, M, Jiang, Y, Lampe, J, Wenzel, J & Schwaninger, M 2019, 'The impact of endothelial cell death in the brain and its role after stroke: A systematic review', Cell Stress, vol. 3, no. 11, pp. 330-347. https://doi.org/10.15698/cst2019.11.203

Ikhsan, M, Palumbo, A, Rose, D, Zille, M & Boltze, J 2019, 'Neuronal Stem Cell and Drug Interactions: A Systematic Review and Meta‐Analysis: Concise Review', Stem Cells Translational Medicine, vol. 8, no. 11, pp. 1202-1211. https://doi.org/10.1002/sctm.19-0020

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