Laboratory of Molecular Psychiatry, Department of Neuropsychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany.
J Cereb Blood Flow Metab. 2013 Mar;33(3):428-39. doi: 10.1038/jcbfm.2012.187. Epub 2012 Dec 19.
Despite its limited regenerative capacity, the central nervous system (CNS) shares more repair mechanisms with peripheral tissues than previously recognized. Scar formation is a ubiquitous healing mechanism aimed at patching tissue defects via the generation of fibrous extracellular matrix (ECM). This process, orchestrated by stromal cells, can unfavorably affect the capacity of tissues to restore function. Vascular mural cells have been found to contribute to scarring after spinal cord injury. In the case of stroke, little is known about the responses of pericytes (PCs) and stromal cells. Here, we show that capillary PCs are rapidly lost after cerebral ischemia in both experimental and human stroke. Coincident with this loss is a massive proliferation of resident platelet-derived growth factor receptor beta (PDGFRβ)(+) and CD105(+) stromal cells, which originate from the neurovascular unit and deposit ECM in the ischemic mouse brain. The presence of PDGFRβ(+) stromal cells demarcates a fibrotic, contracted, and macrophage-laden lesion core from the rim of hypertrophic astroglia in both experimental and human stroke. We suggest that a previously unrecognized population of CNS-resident stromal cells drives a dynamic process of scarring after cerebral ischemia, which appears distinct from the glial scar and represents a novel target for regenerative stroke therapies.
尽管中枢神经系统（CNS）的再生能力有限，但它与外周组织共享的修复机制比以前认为的要多。疤痕形成是一种普遍存在的愈合机制，旨在通过生成纤维细胞外基质（ECM）来修复组织缺陷。这个过程由基质细胞协调，可以不利地影响组织恢复功能的能力。已经发现血管壁细胞在脊髓损伤后会导致疤痕形成。在中风的情况下，关于周细胞（PCs）和基质细胞的反应知之甚少。在这里，我们发现在实验性和人类中风后，大脑缺血后毛细血管 PC 会迅速丢失。与这种丢失同时发生的是大量增殖的常驻血小板衍生生长因子受体β（PDGFRβ）（+）和 CD105（+）基质细胞，这些细胞来源于神经血管单元，并在缺血性小鼠脑中沉积 ECM。PDGFRβ（+）基质细胞的存在将实验性和人类中风中的纤维化、收缩和富含巨噬细胞的病变核心与肥大星形胶质细胞的边缘区分开来。我们认为，中枢神经系统驻留基质细胞的一个以前未被识别的群体在大脑缺血后驱动了一个动态的疤痕形成过程，这与神经胶质疤痕不同，代表了再生性中风治疗的一个新靶点。
