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

2019

Loera-Valencia, R, Zille, M, Boltze, J, Cedazo-Minguez, A, Kenigsberg, PA, Page, G, Duarte, AI, Giusti, P, Zusso, M, Robert, P, Frisoni, GB, Cattaneo, A, Cartier, N, Buee, L, Johansson, G, Johansson, G & Winblad, B 2019, 'Current and emerging avenues for Alzheimer's disease drug targets', Journal of Internal Medicine, vol. 286, no. 4, pp. 398-437. https://doi.org/10.1111/joim.12959

Castillo, X, Castro-Obregón, S, Gutiérrez-Becker, B, Gutiérrez-Ospina, G, Karalis, N, Khalil, AA, Lopez-Noguerola, JS, Lozano Rodríguez, L, Martínez-Martínez, E, Perez-Cruz, C, Pérez-Velázquez, J, Pina, AL, Rubio, K, Salazar García, HP, Syeda, T, Vanoye-Carlo, A, Villringer, A, Winek, K & Zille, M 2019, 'Re-thinking the Etiological Framework of Neurodegeneration', Frontiers in Neuroscience, vol. 13, 728. https://doi.org/10.3389/fnins.2019.00728

Zille, M, Kumar, A, Kundu, N, Bourassa, MW, Wong, VSC, Willis, D, Karuppagounder, SS & Ratan, RR 2019, 'Ferroptosis in Neurons and Cancer Cells Is Similar But Differentially Regulated by Histone Deacetylase Inhibitors', eNeuro, vol. 6, no. 1, 0263-18.2019. https://doi.org/10.1523/ENEURO.0263-18.2019

2018

Rose, D, Schmidt, A, Brandenburger, M, Sturmheit, T, Zille, M & Boltze, J 2018, 'Sulfur mustard skin lesions: A systematic review on pathomechanisms, treatment options and future research directions', Toxicology Letters, vol. 293, pp. 82-90. https://doi.org/10.1016/J.TOXLET.2017.11.039

The Hemorrhagic Stroke Academia Industry (HEADS) Roundtable Participants 2018, 'Basic and Translational Research in Intracerebral Hemorrhage Limitations, Priorities, and Recommendations', Stroke : journal of the American Heart Association, vol. 49, no. 5, pp. 1308-1314. https://doi.org/10.1161/STROKEAHA.117.019539

The Hemorrhagic Stroke Academia Industry (HEADS) Roundtable Participants & Zille, M 2018, 'Unmet Needs and Challenges in Clinical Research of Intracerebral Hemorrhage', Stroke : journal of the American Heart Association, vol. 49, no. 5, pp. 1299-1307. https://doi.org/10.1161/STROKEAHA.117.019541

Modo, MM, Jolkkonen, J, Zille, M & Boltze, J 2018, 'Future of Animal Modeling for Poststroke Tissue Repair', Stroke : journal of the American Heart Association, vol. 49, no. 5, pp. 1099-1106. https://doi.org/10.1161/STROKEAHA.117.018293

Brockmann, I, Ehrenpfordt, J, Sturmheit, T, Brandenburger, M, Kruse, C, Zille, M, Rose, D & Boltze, J 2018, 'Skin-Derived Stem Cells for Wound Treatment Using Cultured Epidermal Autografts: Clinical Applications and Challenges.', Stem Cells International, vol. 2018, 4623615. https://doi.org/10.1155/2018/4623615

2017

Lang, V, Zille, M, Infante-Duarte, C, Jarius, S, Jahn, H, Paul, F, Ruprecht, K & Pina, AL 2017, 'Alzheimer's disease: Elevated pigment epithelium-derived factor in the cerebrospinal fluid is mostly of systemic origin', Journal of the Neurological Sciences, vol. 375, pp. 123-128. https://doi.org/10.1016/j.jns.2017.01.051

Zille, M, Karuppagounder, SS, Chen, Y, Gough, PJ, Bertin, J, Finger, J, Milner, TA, Jonas, EA & Ratan, RR 2017, 'Neuronal Death after Hemorrhagic Stroke in Vitro and in Vivo Shares Features of Ferroptosis and Necroptosis', Stroke : journal of the American Heart Association, vol. 48, no. 4, pp. 1033-1043. https://doi.org/10.1161/STROKEAHA.116.015609

Boehm-Sturm, P, Füchtemeier, M, Foddis, M, Mueller, S, Trueman, RC, Zille, M, Rinnenthal, JL, Kypraios, T, Shaw, L, Dirnagl, U & Farr, TD 2017, 'Neuroimaging Biomarkers Predict Brain Structural Connectivity Change in a Mouse Model of Vascular Cognitive Impairment', Stroke : journal of the American Heart Association, vol. 48, no. 2, pp. 468-475. https://doi.org/10.1161/STROKEAHA.116.014394

ISN&N meeting contributors & Zille, M 2017, 'Recent progress in translational research on neurovascular and neurodegenerative disorders', Restorative Neurology and Neuroscience, vol. 35, no. 1, pp. 87-103. https://doi.org/10.3233/RNN-160690

2015

Karuppagounder, SS, Kumar, A, Shao, DS, Zille, M, Bourassa, MW, Caulfield, JT, Alim, I & Ratan, RR 2015, 'Metabolism and epigenetics in the nervous system: Creating cellular fitness and resistance to neuronal death in neurological conditions via modulation of oxygen-, iron-, and 2-oxoglutarate-dependent dioxygenases', Brain Research, vol. 1628, no. B, pp. 273-287. https://doi.org/10.1016/j.brainres.2015.07.030

Yusuf Terzi, M, Casalis, P, Lang, V, Zille, M, Bründl, E, Störr, E-M, Brawanski, A, Vajkoczy, P, Thomale, U & Pina, AL 2015, 'Effects of pigment epithelium-derived factor on traumatic brain injury', Restorative Neurology and Neuroscience, vol. 33, no. 1, pp. 81-93. https://doi.org/10.3233/RNN-140417

2014

Zille, M, Riabinska, A, Terzi, MY, Balkaya, M, Prinz, V, Schmerl, B, Nieminen-Kelhae, M, Endres, M, Vajkoczy, P & Pina, AL 2014, 'Influence of Pigment Epithelium-Derived Factor on Outcome after Striatal Cerebral Ischemia in the Mouse', PLoS ONE, vol. 9, no. 12, e114595. https://doi.org/10.1371/journal.pone.0114595

Zille, M, Harhausen, D, Saint-Hubert, MD, Michel, R, Reutelingsperger, CP, Dirnagl, U & Wunder, A 2014, 'A Dual-Labeled Annexin A5 is not Suited for SPECT Imaging of Brain Cell Death in Experimental Murine Stroke', Journal of Cerebral Blood Flow & Metabolism, vol. 34, no. 9, pp. e1-e7. https://doi.org/10.1038/jcbfm.2014.115

Schoknecht, K, Prager, O, Vazana, U, Kamintsky, L, Harhausen, D, Zille, M, Figge, L, Chassidim, Y, Schellenberger, E, Kovacs, R, Heinemann, U & Friedman, A 2014, 'Monitoring stroke progression: in vivo imaging of cortical perfusion, blood-brain barrier permeability and cellular damage in the rat photothrombosis model', Journal of Cerebral Blood Flow & Metabolism, vol. 34, no. 11, pp. 1791-1801. https://doi.org/10.1038/jcbfm.2014.147

Haeckel, A, Appler, F, Figge, L, Kratz, H, Lukas, M, Michel, R, Schnorr, J, Zille, M, Hamm, B & Schellenberger, E 2014, 'XTEN-Annexin A5: XTEN Allows Complete Expression of Long-Circulating Protein-Based Imaging Probes as Recombinant Alternative to PEGylation', Journal of Nuclear Medicine, vol. 55, no. 3, pp. 508-514. https://doi.org/10.2967/JNUMED.113.128108

Stöber, F, Baldauf, K, Ziabreva, I, Harhausen, D, Zille, M, Neubert, J, Reymann, KG, Scheich, H, Dirnagl, U, Schröder, UH, Wunder, A & Goldschmidt, J 2014, 'Single-cell resolution mapping of neuronal damage in acute focal cerebral ischemia using thallium autometallography', Journal of Cerebral Blood Flow and Metabolism, vol. 34, no. 1, pp. 144-152. https://doi.org/10.1038/jcbfm.2013.177

2013

Harhausen, D, Sudmann, V, Khojasteh, U, Müller, J, Zille, M, Graham, K, Thiele, A, Dyrks, T, Dirnagl, U & Wunder, A 2013, 'Specific Imaging of Inflammation with the 18kDa Translocator Protein Ligand DPA-714 in Animal Models of Epilepsy and Stroke', PLoS ONE, vol. 8, no. 8, e69529. https://doi.org/10.1371/journal.pone.0069529

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