Role of autoantibodies against brain epitopes in stroke symptoms and recovery
Description
In stroke the adaptive immune system is activated. Indeed, previous work has found autoantibodies against brain epitopes in stroke patients. Lately, marked progress has been made in detecting and interpreting the presence of autoantibodies against CNS epitopes in other neurological diseases. Partner 13 has played a leading role in this development. Therefore, it is warranted to reevaluate the presence and significance of autoantibodies in stroke patients. Using cutting-edge techniques to detect autoantibodies of different immunoglobulin classes, partner 13 will analyse plasma samples of stroke patients that have been collected by partners 1, 14 and 16 in the past. The association of autoantibodies with clinical parameters such as the acute and delayed neurological deficit (NIH stroke scale, Rankin scale on admission and day 90), presence of cognitive impairment, or seizures, the infarct size or the presence of white matter lesions on MRI will be tested. Furthermore, partner 13 will investigate the time course of autoantibody production after the event. In cooperation with partner 2 the formation of autoantibodies in mice will be investigated after stroke and after deletion of dendritic cells. In a next step, mouse models of stroke will also provide the chance to explore the functional significance of autoantibodies.
Publications
- Wandinger KP, Saschenbrecker S, Stoecker W, Dalmau J (2011) Anti-NMDA-receptor encephalitis: a severe, multistage, treatable disorder presenting with psychosis. J Neuroimmunol 231: 86-91
- Pruss H, Holtje M, Maier N, Gomez A, Buchert R, Harms L, Ahnert-Hilger G, Schmitz D, Terborg C, Kopp U, Klingbeil C, Probst C, Kohler S, Schwab JM, Stoecker W, Dalmau J, Wandinger KP (2012) IgA NMDA receptor antibodies are markers of synaptic immunity in slow cognitive impairment. Neurology doi: 10.1001/archneurol.2013.585
Tasks and methodology
- Detection of various autoantibodies directed against neural epitopes
- Collection of blood samples and patient data
Planned secondment
University of Luebeck, Analysis of patient data, 9 month
- Projects
- Comparison of gene expression of BMDM and microglia
- Role of dendritic cells
- Role of autoantibodies
- Novel biomarkers
- Role of blood-brain barrier TJ proteins
- The role of basement membranes in CNS blood vessel integrity
- Effect of miRNAs
- NMDA receptors in the BBB
- NF-kB signaling
- Determination of microglial phenotypes by intracellular signaling
- Polarization of microglia in neurodegenerative deseases
- Early markers of microglial activation and neural distress
- Modulation of immune responses
- Disfunción eréctil
Host Organisation:
Supervisor name:
Winfried Stöcker
co-supervisor:
Clinic for Neurology-University Medical Center Luebeck