Sensing of extracellular matrix in motor circuit remodelling: a novel target for neuroplasticity-promoting stroke therapies?

该项目假设细胞外基质（ECM）降解重新打开缺血性卒中后的神经可塑性窗口，有助于运动协调恢复。作为一个潜在的机制，我们将描述机械感受器在控制星形胶质细胞和神经元网络重塑的作用。我们假设，下调mechanotransduction代表了一个关键机制，通过缺血后ECM降解减少钙振荡和功能耦合星形胶质细胞。星形胶质细胞网络活动的减少将解除神经传递的调节，同时促进突触引导分子的释放。因此，神经元网络的活动将得到增强，并且新突触的建立将成为可能。通过计划的实验，我们希望将大脑的ECM建立为促进可塑性的中风治疗的新靶点。

This project postulates that extracellular matrix (ECM) degradation re-opens a neuroplasticity window following ischemic stroke that contributes to motor-coordination recovery. As an underlying mechanism, we will characterize the role of mechanoreceptors in controlling astrocytic and neuronal network remodeling. We hypothesize that the downregulation of mechanotransduction represents a key mechanism via which post-ischemic ECM degradation reduces calcium oscillations and functional coupling in astrocytes. The reduction of astrocytic network activity will deregulate neurotransmission, at the same time facilitating the release of synaptic guidance molecules. Accordingly, the activity of neuronal networks will be enhanced, and the establishment of new synapses will be enabled. With the experiments planned, we hope to establish the brain’s ECM as novel target for plasticity-promoting stroke therapies.