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

在上一个资助期，我们可以证明P2X7受体对中风预后的重要性。通过使用特定的纳米体阻断P2X7，我们改善了卒中预后。现在，我们计划分析P2X7的下游信号传导，导致gasdermin D （GSDMD）的激活。本提案的主要目的是分析GSDMD在卒中中的作用及其对卒中恢复的影响。我们将使用阻滞剂来调节脑卒中急性期和恢复期小胶质细胞和脑卒中诱导焦亡的GSDMD。为了区分这些药物的多效性作用和对GSDMD的细胞特异性作用，我们将使用可诱导的细胞特异性Caspase-1敲除动物。我们计划制造一种抗GSDMD的纳米体，我们希望将其发展成为中风的治疗选择。

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.