ImmunoStroke: From Immune Cells to Stroke RecoveryThe role of gasdermin D in ischemic stroke

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In the last funding period, we could demonstrate the importance of the P2X7 receptor for stroke outcome. By blocking P2X7 with a specific nanobody, we improved stroke outcome. Now, we plan to analyze the downstream signaling of P2X7, which lead to the activation of gasdermin D (GSDMD). The main goal of this proposal is to analyze the role of GSDMD in stroke and its consequences for stroke recovery. We will use blockers to modulate GSDMD in microglia and stroke-induced pyroptosis in the acute and during the recovery phase of stroke. To distinguish the pleiotropic effects of these drugs from effects on GSDMD in a cell specific manner, we will use inducible cell specific Caspase-1 knockout animals. We plan to generate a nanobody against GSDMD which we hope to develop into a treatment option for stroke.