Local TH transport and action in ischaemic brain injury

 

Dr. Friederike Langhauser,  Prof. Dr. Dagmar Führer &  Prof. Dr. Christoph Kleinschnitz

Aim of this project is to clarify the time- and cell-specific requirements of TH transport and action for improved outcome in ischaemic brain injury. Cell-specific TH transporter KO mice will be analysed in the experimental stroke model of transient middle cerebral artery occlusion (MCAO) to elucidate the role of TH transport in different cell-types of the blood brain barrier. Treatment with T3 at different dosages and time points will be used to identify the optimal conditions for intervention. The impact of TH on stroke outcome will be analysed by functional, morphological and imaging techniques, e.g. light sheet microscopy and spatial proteomics.

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Project Team Member

 

 

Further Information

Homepage Team Langhauser

Homepage Team Kleinschnitz

Selected Publications

 

Casas AI, Kleikers PW, Geuss E, Langhauser F, Adler T, Busch DH, Gailus-Durner V, de Angelis MH, Egea J, Lopez MG, Kleinschnitz C, Schmidt HH. Calcium-dependent blood-brain barrier breakdown by NOX5 limits postreperfusion benefit in stroke. J Clin Invest 2019, 130:1772-1778.

Langhauser F, Casas AI, Dao VT, Guney E, Menche J, Geuss E, Kleikers PWM, López MG, Barabási AL, Kleinschnitz C, Schmidt HHHW. A diseasome cluster-based drug repurposing of soluble guanylate cyclase activators from smooth muscle relaxation to direct neuroprotection. NPJ Syst Biol Appl 2018, 4:8.

Langhauser F, Kraft P, Göb E, Leinweber J, Schuhmann MK, Lorenz K, Gelderblom M, Bittner S, Meuth SG, Wiendl H, Magnus T, Kleinschnitz C. Blocking of α4 integrin does not protect from acute ischemic stroke in mice. Stroke 2014, 45:1799-806.

Bieber M, Werner RA, Tanai E, Hofmann U, Higuchi T, Schuh K, Heuschmann PU, Frantz S, Ritter O, Kraft P, Kleinschnitz C. Stroke-induced chronic systolic dysfunction driven by sympathetic overactivity. Ann Neurol 2017, 82:729-43.

Göbel K, Pankratz S, Asaridou CM, Herrmann AM, Bittner S, Merker M, Ruck T, Glumm S, Langhauser F, Kraft P, Krug TF, Breuer J, Herold M, Gross CC, Beckmann D, Korb-Pap A, Schuhmann MK, Kuerten S, Mitroulis I, Ruppert C, Nolte MW, Panousis C, Klotz L, Kehrel B, Korn T, Langer HF, Pap T, Nieswandt B, Wiendl H, Chavakis T, Kleinschnitz C and Meuth SG. Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells. Nat Commun 2016, 7:11626.

Bittner S, Ruck T, Schuhmann MK, Herrmann AM, Moha ou Maati H, Bobak N, Göbel K, Langhauser F, Stegner D, Ehling P, Borsotto M, Pape HC, Nieswandt B, Kleinschnitz C, Heurteaux C, Galla HJ, Budde T, Wiendl H, Meuth SG. Endothelial TWIK-related potassium channel-1 (TREK1) regulates immune-cell trafficking into the CNS. Nat Med 2013, 19:1161-5.

Kleinschnitz C, Kraft P, Dreykluft A, Hagedorn I, Göbel K, Schuhmann MK, Langhauser F, Helluy X, Schwarz T, Bittner S, Mayer CT, Brede M, Varallyay C, Pham M, Bendszus M, Jakob P, Magnus T, Meuth SG, Iwakura Y, Zernecke A, Sparwasser T, Nieswandt B, Stoll G and Wiendl H. Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature. Blood 2013, 121:679-91.

Langhauser F, Göb E, Kraft P, Geis C, Schmitt J, Brede M, Göbel K, Helluy X, Pham M, Bendszus M, Jakob P, Stoll G, Meuth SG, Nieswandt B, McCrae KR, Kleinschnitz C. Kininogen deficiency protects from ischemic neurodegeneration in mice by reducing thrombosis, blood-brain barrier damage, and inflammation. Blood 2012, 120:4082-92