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                                            3. Plesnila Lab

                                            Plesnila Lab – Laboratory of Experimental Stroke Research

                                            • Research Focus
                                            • Publications
                                            • Team
                                            Visual Plesnila Group

                                            The main interest of the laboratory is to study the role of cerebral vessels for the pathophysiology of acute and chronic brain injury and to use the evolving knowledge for the development of novel therapeutic strategies for patients. For this purpose we use clinically relevant mouse models for acute and chronic brain injury and investigate neuro-vascular morphology and function by in vivo microscopy using conventional and 2-photon fluorescence microscopy.

                                            The work of the Laboratory of Experimental Stroke Research currently focuses around two topics: 1) the role of the cerebral microcirculation for brain injury after subarachnoid hemorrhage (SAH) and 2) the function of cerebral microvessels in physiological and pathological aging. Regarding SAH we discovered that early surgical decompression results in an increased rate of secondary bleedings thereby significantly worsening outcome and that inhaled nitric oxide reduces cerebral microvasospasms by -85% and blunts mortality. Further, we demonstrated that pial and intraparenchymal microvessels show a complete loss of CO2 reactivity after SAH. This finding suggests that SAH induces severe neuro-vascular dysfunction already within the first few hours after brain hemorrhage. Experiments on the aging brain demonstrated that already normal aging results in severe dysfunction of cerebral microvessels. While young vessels dilate and remain dilated upon repetitive neuronal activation, vessels from only eight month old mice dilate less and start to constrict with ongoing neuronal activity. These findings suggest that rather vascular and not necessarily neuronal dysfunction may be responsible for the reduced attention span at older age. Finally, we could demonstrate that the first pathological alteration in a mouse model of CADASIL is the retraction and death of microvascular pericytes. As a consequence the blood brain barrier becomes dysfunctional, plasma proteins enter the brain, and astrocytic end-feed detach from cerebral capillaries. These changes start to occur at an age of 4-8 month and precede white matter damage by more than one year. Accordingly, pericytes may represent the primary target for the cure of CADASIL.

                                            Figure (top): Mural cells expressing EGFP and DsRed under the PDGFRb and NG2 promoters line the cortical vasculature; labelling smooth muscle cells, fibroblasts and pericytes within the mouse cortex.

                                            Contact: Prof. Dr. med. Nikolaus Plesnila
                                            Tel: +49-89-4400-46219
                                            E-Mail: nikolaus.plesnila@med.uni-muenchen.de

                                            Sectretary: Hedwig Pietsch
                                            Tel: +49-89-4400-46220
                                            E-Mail: hedwig.pietsch@med.uni-muenchen.de

                                            experimental-research

                                            Publications by Nick Plesnila

                                            Key Publications

                                            > All Publications

                                            2021

                                            Auffenberg E, Hedrich UB, Barbieri R, Miely D, Groschup B, Wuttke TV, Vogel N, Lührs P, Zanardi I, Bertelli S, Spielmann N, Gailus-Durner V, Fuchs H, Hrabě de Angelis M, Pusch M, Dichgans M, Lerche H, Gavazzo P, Plesnila N, Freilinger T. Hyperexcitable interneurons trigger cortical spreading depression in an Scn1a migraine model. J Clin Invest. 2021 Nov 1;131(21):e142202. doi: 10.1172/JCI142202. 

                                            Liu H, Schwarting J, Terpolilli NA, Nehrkorn K, Plesnila N. Scavenging Free Iron Reduces Arteriolar Microvasospasms After Experimental Subarachnoid Hemorrhage. Stroke. 2021 Dec;52(12):4033-4042. doi: 10.1161/STROKEAHA.120.033472. Epub 2021 Nov 9. 

                                            Seker FB, Fan Z, Gesierich B, Gaubert M, Sienel RI, Plesnila N. Neurovascular Reactivity in the Aging Mouse Brain Assessed by Laser Speckle Contrast Imaging and 2-Photon Microscopy: Quantification by an Investigator-Independent Analysis Tool. Front Neurol. 2021 Nov 11;12:745770. doi: 10.3389/fneur.2021.745770.

                                            Khalin I, Severi C, Heimburger D, Wehn A, Hellal F, Reisch A, Klymchenko AS, Plesnila N. Dynamic tracing using ultra-bright labeling and multi-photon microscopy identifies endothelial uptake of poloxamer 188 coated poly(lactic-co-glycolic acid) nano-carriers in vivo. Nanomedicine. 2021 Dec 13;40:102511. doi: 10.1016/j.nano.2021.102511. Epub ahead of print. 

                                            2020

                                            Khalin I, Heimburger D, Melnychuk N, Collot M, Groschup B, Hellal F, Reisch A, Plesnila N, Klymchenko AS. Ultrabright Fluorescent Polymeric Nanoparticles with Stealth Pluronic Shell for Live Tracking in Mouse Brain. ACS Nano. 2020 Jul 17. Epub ahead of print. 

                                            2019

                                            Panahpour H, Terpolilli NA, Schaffert D, Culmsee C, Plesnila N. Central Application of Aliskiren, a Renin Inhibitor, Improves Outcome After Experimental Stroke Independent of Its Blood Pressure Lowering Effect. Front Neurol. 2019 Sep 4;10:942. 

                                            Anzabi M, Angleys H, Aamand R, Ardalan M, Mouridsen K, Rasmussen PM, Sørensen JCH, Plesnila N, Østergaard L, Iversen NK. Capillary flow disturbances after experimental subarachnoid hemorrhage: A contributor to delayed cerebral ischemia? Microcirculation. 2019 Apr;26(3):e12516. 

                                            2018

                                            Ganjam GK, Terpolilli NA, Diemert S, Eisenbach I, Hoffmann L, Reuther C, Herden C, Roth J, Plesnila N, Culmsee C. Cylindromatosis mediates neuronal cell death in vitro and in vivo. Cell Death Differ. 2018 Aug;25(8):1394-1407. 

                                            Frik J, Merl-Pham J, Plesnila N, Mattugini N, Kjell J, Kraska J, Gómez RM, Hauck SM, Sirko S, Götz M. Cross-talk between monocyte invasion and astrocyte proliferation regulates scarring in brain injury. EMBO Rep. 2018 May;19(5). 

                                            Liu H, Dienel A, Schöller K, Schwarzmaier SM, Nehrkorn K, Plesnila N, Terpolilli NA. Microvasospasms After Experimental Subarachnoid Hemorrhage Do Not Depend on Endothelin A Receptors. Stroke. 2018 Mar;49(3):693-699. 

                                            2017

                                            Balbi M, Koide M, Wellman GC, Plesnila N. Inversion of neurovascular coupling after subarachnoid hemorrhage in vivo. J Cereb Blood Flow Metab. 2017 Nov;37(11):3625-3634.

                                            2016

                                            Terpolilli NA, Feiler S, Dienel A, Müller F, Heumos N, Friedrich B, Stover J, Thal S, Schöller K, Plesnila N. Nitric oxide inhalation reduces brain damage, prevents mortality, and improves neurological outcome after subarachnoid hemorrhage by resolving early pial microvasospasms. J Cereb Blood Flow Metab. 2016 Dec;36(12):2096-2107. 

                                            Lourbopoulos A, Mamrak U, Roth S, Balbi M, Shrouder J, Liesz A, Hellal F, Plesnila N. Inadequate food and water intake determine mortality following stroke in mice. J Cereb Blood Flow Metab. 2017 Jun;37(6):2084-2097. 

                                            2015

                                            Bühler D, Azghandi S, Schüller K, Plesnila N. Effect of decompressive craniectomy on outcome following subarachnoid hemorrhage in mice. Stroke. 2015 Mar;46(3):819-26. 

                                            Schwarzmaier SM, Gallozzi M, Plesnila N. Identification of the Vascular Source of Vasogenic Brain Edema following Traumatic Brain Injury Using In Vivo 2-Photon Microscopy in Mice. J Neurotrauma. 2015 Jul 1;32(13):990-1000. 

                                            Balbi M, Ghosh M, Longden TA, Jativa Vega M, Gesierich B, Hellal F, Lourbopoulos A, Nelson MT, Plesnila N. Dysfunction of mouse cerebral arteries during early aging. J Cereb Blood Flow Metab. 2015 Sep;35(9):1445-53. 

                                            Terpolilli NA, Brem C, Bühler D, Plesnila N. Are We Barking Up the Wrong Vessels? Cerebral Microcirculation After Subarachnoid Hemorrhage. Stroke. 2015 Oct;46(10):3014-9. 

                                            Ghosh M, Balbi M, Hellal F, Dichgans M, Lindauer U, Plesnila N. Pericytes are involved in the pathogenesis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Ann Neurol. 2015 Dec;78(6):887-900. 

                                            Balbi M, Koide M, Schwarzmaier SM, Wellman GC, Plesnila N. Acute changes in neurovascular reactivity after subarachnoid hemorrhage in vivo. J Cereb Blood Flow Metab. 2017 Jan;37(1):178-187. 

                                            2014

                                            Friedrich B, Michalik R, Oniszczuk A, Abubaker K, Kozniewska E, Plesnila N. CO2 has no therapeutic effect on early microvasospasm after experimental subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2014 Aug;34(8):e1-6. 

                                            2013

                                            Terpolilli NA, Kim SW, Thal SC, Kuebler WM, Plesnila N. Inhaled nitric oxide reduces secondary brain damage after traumatic brain injury in mice. J Cereb Blood Flow Metab. 2013 Feb;33(2):311-8.

                                            Schwarzmaier SM, Zimmermann R, McGarry NB, Trabold R, Kim SW, Plesnila N. In vivo temporal and spatial profile of leukocyte adhesion and migration after experimental traumatic brain injury in mice. J Neuroinflammation. 2013 Feb 28;10:32. 

                                            Rauen K, Trabold R, Brem C, Terpolilli NA, Plesnila N. Arginine vasopressin V1a receptor-deficient mice have reduced brain edema and secondary brain damage following traumatic brain injury. J Neurotrauma. 2013 Aug 15;30(16):1442-8. 

                                            2012

                                            Terpolilli NA, Kim SW, Thal SC, Kataoka H, Zeisig V, Nitzsche B, Klaesner B, Zhu C, Schwarzmaier S, Meissner L, Mamrak U, Engel DC, Drzezga A, Patel RP, Blomgren K, Barthel H, Boltze J, Kuebler WM, Plesnila N. Inhalation of nitric oxide prevents ischemic brain damage in experimental stroke by selective dilatation of collateral arterioles. Circ Res. 2012 Mar 2;110(5):727-38. 

                                            Hockel K, Schöller K, Trabold R, Nussberger J, Plesnila N. Vasopressin V(1a) receptors mediate posthemorrhagic systemic hypertension thereby determining rebleeding rate and outcome after experimental subarachnoid hemorrhage. Stroke. 2012 Jan;43(1):227-32. 

                                            Friedrich B, Müller F, Feiler S, Schöller K, Plesnila N. Experimental subarachnoid hemorrhage causes early and long-lasting microarterial constriction and microthrombosis: an in-vivo microscopy study. J Cereb Blood Flow Metab. 2012 Mar;32(3):447-55. 

                                            2010

                                            Trabold R, Erös C, Zweckberger K, Relton J, Beck H, Nussberger J, Müller-Esterl W, Bader M, Whalley E, Plesnila N. The role of bradykinin B(1) and B(2) receptors for secondary brain damage after traumatic brain injury in mice. J Cereb Blood Flow Metab. 2010 Jan;30(1):130-9. 

                                            2008

                                            Slemmer JE, Zhu C, Landshamer S, Trabold R, Grohm J, Ardeshiri A, Wagner E, Sweeney MI, Blomgren K, Culmsee C, Weber JT, Plesnila N. Causal role of apoptosis-inducing factor for neuronal cell death following traumatic brain injury. Am J Pathol. 2008 Dec;173(6):1795-805.

                                            von Baumgarten L, Trabold R, Thal S, Back T, Plesnila N. Role of cortical spreading depressions for secondary brain damage after traumatic brain injury in mice. J Cereb Blood Flow Metab. 2008 Jul;28(7):1353-60. 

                                            2005

                                            Culmsee C, Zhu C, Landshamer S, Becattini B, Wagner E, Pellecchia M, Blomgren K, Plesnila N. Apoptosis-inducing factor triggered by poly(ADP-ribose) polymerase and Bid mediates neuronal cell death after oxygen-glucose deprivation and focal cerebral ischemia. J Neurosci. 2005 Nov 2;25(44):10262-72.

                                            Gröger M, Lebesgue D, Pruneau D, Relton J, Kim SW, Nussberger J, Plesnila N. Release of bradykinin and expression of kinin B2 receptors in the brain: role for cell death and brain edema formation after focal cerebral ischemia in mice. J Cereb Blood Flow Metab. 2005 Aug;25(8):978-89. 

                                            2004

                                            Plesnila N, Zhu C, Culmsee C, Gröger M, Moskowitz MA, Blomgren K. Nuclear translocation of apoptosis-inducing factor after focal cerebral ischemia. J Cereb Blood Flow Metab. 2004 Apr;24(4):458-66. 

                                            See all publications by Nikolaus Plesnila


                                            Plesnila, Nikolaus, Prof. Dr. med. / PI

                                            Braun, Chiara / MD student

                                            Cara, Ardela / MD student

                                            Corvin, Christian / MD student

                                            Exner, Carina / MD 

                                            Filser, Severin, Dr. / Postdoc

                                            Groschup, Bernhard / PhD student

                                            Guo, Yinghuimin / MD student

                                            Kamm, Katharina / Clinician Scientist (neu)

                                            Khalin, Igor Dr. / Postdoc

                                            Krestel, Eva / MD student

                                            Lin, Xianjiang / MD, PhD student

                                            Lourbopoulos, Anathasios, Dr. med. / Clinician Scientist

                                            Mamrak, Uta / technical assistant

                                            Rauen, Katrin, Dr. / Clinician Scientist

                                            Şeker, Burcu, Dr. / Postdoc

                                            Schwarzmaier, Susanne, Dr / Clinician Scientist

                                            Schwarting, Julian / Clinician Scientist

                                            Shrouder, Joshua / PhD student

                                            Sienel, Rebecca / PhD student

                                            Terpolilli, Nicole, Dr. / Clinician Scientist

                                            Umeasalugo, Kosisochukwu / PhD student

                                            Yoshimura, Sodai, MD, PhD / visiting researcher

                                            Wehn, Antonia / MD student

                                            Pietsch, Hedwig / Team Assistant


                                            Contact: Prof. Dr. med. Nikolaus Plesnila
                                            Tel: +49-89-4400-46219

                                            E-Mail: nikolaus.plesnila@med.uni-muenchen.de

                                            Sectretary: Hedwig Pietsch
                                            Tel: +49-89-4400-46220
                                            E-Mail: hedwig.pietsch@med.uni-muenchen.de

                                            Contact

                                            Institute for Stroke and Dementia Research (ISD)
                                            University Hospital, LMU Munich

                                            Director: Prof. Dr. med. Martin Dichgans

                                            Feodor-Lynen-Straße 17
                                            81377 Munich, Germany

                                            Phone: +49 (0)89 4400 46019
                                            www.isd-research.de
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