The role of the S1P signalling pathway on astrocyte polarization after ischemic stroke – functional outcome, inflammation and neurodegeneration (B08)

• Subject Area: Pharmacology ; Molecular and Cellular Neurology and Neuropathology
• Term: since 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 204083920

Reaktive astrogliosis plays a decisive functional role after ischemic stroke. During the formation of the astroglial scar, astrocytes adopt differential pro- and anti-inflammtory functions that modulate inflammation and neurodegeneration. Multiple Sclerosis research has unveiled an important function for the astrocytic S1P receptor 1 in the therapeutic effects of fingolimod and we have collected first pieces of evidence for a differential regulation of S1P receptors in different cytokine milieus. Besides that, we found that astrocyte polarization into the pro-inflammatory A1 astrocytes and the anti-inflammtory A2 astrocytes is modulated by astrocytic S1P receptor expression in a counteractive way. During the course of the upcoming funding period, we aim to characterize the role of the S1P signalling pathway in astrocyte polarization after stroke and to test its therapeutic potential in animal models of stroke.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1039: Signalling by Fatty Acid Derivatives and Sphingolipids in Health and Disease
• Applicant Institution: Goethe-Universität Frankfurt am Main
• Project Heads: Dr. Robert Brunkhorst, until 3/2020; Dr. Roxane-Isabelle Kestner; Professorin Dr. Waltraud Pfeilschifter