Cerebrovascular Pharmacology

(Foto: 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. Mechanisms of axonal degeneration and cell death after brain hemorrhage and ischemic stroke

  2. Hypertension as a model to understand the lifespan vascular changes leading to cerebrovascular diseases

  3. Understanding the mechanisms of cell death after subretinal hemorrhage

  4. Aging of the blood-brain barrier

  5. Identifying bioactive compounds for healthy brain aging

Funding

  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

    2. 2018-2020: Fraunhofer Society MEF EnTireAxon – Test system to systematically investigate axons

    3. 2018-2019: Interstellar Initiative of the Japan Agency for Medical Research and Development and the New York Academy of Sciences

    4. 2018-2019: BMBF MERCEDES – Multimodal Enhancement of Nerve Tissue Regeneration using Cellular Approaches for Degenerative Nervous System diseases

    5. 2018-2019: BMBF NEPTUN – German-Mexican Roundtable Exploring New Etiological Paths Towards Neurodegeneration

    Selected Publications

    • Chhatwal S, Antony H, Lamei S, Kovács-Öller T, Klettner AK, Zille M. A systematic review of the cell death mechanisms in retinal pigment epithelium cells and photoreceptors after subretinal hemorrhage - Implications for treatment options. Biomed Pharmacother. 2023. doi: 10.1016/j.biopha.2023.115572
    • Zille M, Farr TD, Keep RF, Römer C, Xi G, Boltze J. Novel targets, treatments, and advanced models for intracerebral hemorrhage. EBioMedicine. 2022. doi: 10.1016/j.ebiom.2022.103880
    • Zille M, Oses-Prieto JA, Savage SR, Karuppagounder SS, Chen Y, Kumar A, Morris JH, Scheidt KA, Burlingame AL, Ratan RR. Hemin-induced death models hemorrhagic stroke and is a variant of classical neuronal ferroptosis. J Neurosci. 2022. doi: 10.1523/JNEUROSCI.0923-20.2021.
    • 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, Coelho C, Franz J, Spiecker F, Lembrich B, Binder S, Feller N, König P, Busch H, Collin L, Villasenor R, Jöhren O, Altmeppen H, 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. The SARS-CoV-2 main protease Mpro causes microvascular brain pathology by cleaving NEMO in brain endothelial cells. Nat Neurosci. (2021). https://doi.org/10.1038/s41593-021-00926-1
    • Dörschmann P, Apitz S, Hellige I, Neupane S, Bittkau KS, Alban S, Kopplin G, Ptak S, Fretté X, Roider J, Zille M*, Klettner AK*. Evaluation of protective effects of fucoidans from Fucus species and Laminaria hyperborea against oxidative stress and iron-induced cell death. Mar. Drugs. 2021, 19, 557. doi: 10.3390/md19100557.
    • Palumbo A, Grüning P, Landt SK, Heckmannn L, Bartram L, Pabst A, Flory C, Ikhsan M, Pietsch S, Schulz R, Kren C, Koop N, Boltze J, Madany Mamlouk A, Zille M. Deep learning to decipher the progression and morphology of axonal degeneration. Cells. 2021, 10, 2539. doi: 10.3390/cells10102539.
    • Krueger K, Boehme E, Klettner AK*, Zille M*. The potential of marine resources for retinal diseases: a systematic review on the molecular mechanisms. Crit Rev Food Sci Nutr. 2021 May 10:1-44. doi: 10.1080/10408398.2021.1915242.
    • Riabinska A*, Zille M*, Terzi MY, Cordell R, Nieminen-Kelhä M, Klohs J, Piña AL. Influence of Pigment Epithelium-Derived Factor on the Blood-Brain Barrier in Normal and Ischemic Mouse Brain. Cell Mol Neurobiol. 2020 Jul;40(5):751-764. doi: 10.1007/s10571-019-00770-9.  Epub 2019 Dec 20.
    • Zille M, Ikhsan M, Jiang Y, Lampe J, Wenzel J, Schwaninger M. The impact of endothelial cell death in the brain and its role after stroke: A systematic review. Cell Stress. 2019, 3(11): 330-347. doi: 10.15698/cst2019.11.203.
    • Castillo X, Castro Obregón S, Gutiérrez Becker B, Gutiérrez-Ospina G, Karalis N, Khalil A, Lopez-Noguerola JS, Lozano Rodríguez L, Martínez-Martínez E, Perez-Cruz C, Pérez Velázquez J, Pina AL, Rubio K, Salazar Garcia HP, Syeda T, Vanoye Carlo A, Villringer A, Winek K, Zille M. Re-thinking the etiological framework of neurodegeneration. Front Neurosci. 2019 Jul 24;13:728. doi:10.3389/fnins.2019.00728. eCollection 2019.
    • Zille M, Karuppagounder SS, Ratan RR. Ferroptosis in Neurons and Cancer Cells is Similar but Differentially Regulated by HDAC Inhibitors. eNeuro. 2019 Feb 15;6(1). pii: ENEURO.0263-18.2019. doi: 10.1523/ENEURO.0263-18.2019. eCollection 2019 Jan-Feb.
    • Hemorrhagic Stroke Academia Industry (HEADS) Roundtable Participants. Selim M, Hanley D, Broderick J, Keep R, Shoamanesh A, Ziai W, Singh V, Sheth K, Rosenblum M, Palesch Y, Muehlschlegel S, Kersten J, Mendelow DA, Gurol E, Gonzales N, Falcone G, Gregson B, Goldstein J, Zille M, Xi G, Ratan RR, James M, Sansing L, Aronowski J, Genstler C. Unmet Needs and Challenges in Clinical Research of Intracerebral Hemorrhage. Stroke. 2018 May;49(5):1299-1307. doi: 10.1161/STROKEAHA.117.019541. Epub 2018 Apr 4.
    • Hemorrhagic Stroke Academia Industry (HEADS) Roundtable Participants. Selim M, Hanley D, Keep R, Aronowski J, Genstler C, James M, Ratan RR, Sansing L, Youd A, Xi G, Zille M, Broderick J, Goldstein J, Gregson B, Falcone G, Gonzales N, Gurol E, Kersten J, Lewkowicz H, Mendelow DA, Muehlschlegel S, Neuman R, Palesch Y, Rosenblum M, Sheth K, Singh V, Ziai W, Anderson C, Awad I, Bastings E, Bednar M, Coon A, Gottesman R, Katz B, Khan S, Koroshetz W, Moy C, Koenig J, Torbey M, Vespa P, Steiner T, Zucarrello M, Wakhloo A, Tymianski M, Shoamanesh A, Pollack C, Marler J, Ling S, Loftus C, Louis T, Pena C, Omert L, Singer M, Zheng X, Keita M, Braun B, and Norton C. Basic and Translational Research in Intracerebral Hemorrhage: Limitations, Priorities, and Recommendations. Stroke. 2018 May;49(5):1308-1314. doi: 10.1161/STROKEAHA.117.019539. Epub 2018 Apr 4.
    • Zille M, Karuppagounder SS, Chen Y, Gough PJ, Bertin J, Finger J, Milner TA, Jonas EA, Ratan RR. Neuronal Death After Hemorrhagic Stroke In Vitro and In Vivo Shares Features of Ferroptosis and Necroptosis. Stroke. 2017 Apr;48(4):1033-1043. doi: 10.1161/STROKEAHA.116.015609. Epub 2017 Mar 1.

     

    Publications in Pubmed: https://pubmed.ncbi.nlm.nih.gov/?term=(Zille%20M)%20NOT%20Stolle%20A