Glial Cell Line-Derived Neurotrophic Factor and Focal Ischemic Stroke

Abstract

Focal ischemic stroke (FIS) is a leading cause of human debilitation and death. Following the onset of a FIS, the brain experiences a series of spatiotemporal changes which are exemplified in different pathological processes. One prominent feature of FIS is the development of reactive astrogliosis and glial scar formation in the peri-infarct region (PIR). During the subacute phase, astrocytes in PIR are activated, referred to as reactive astrocytes (RAs), exhibit changes in morphology (hypotrophy), show an increased proliferation capacity, and altered gene expression profile, a phenomenon known as reactive astrogliosis. Subsequently, the morphology of RAs remains stable, and proliferation starts to decline together with the formation of glial scars. Reactive astrogliosis and glial scar formation eventually cause substantial tissue remodeling and changes in permanent structure around the PIR. Glial cell line-derived neurotrophic factor (GDNF) was originally isolated from a rat glioma cell-line and regarded as a potent survival neurotrophic factor. Under normal conditions, GDNF is expressed in neurons but is upregulated in RAs after FIS. This review briefly describes properties of GDNF, its receptor-mediated signaling pathways, as well as recent studies regarding the role of RAs-derived GDNF in neuronal protection and brain recovery. These results provide evidence suggesting an important role of RA-derived GDNF in intrinsic brain repair and recovery after FIS, and thus targeting GDNF in RAs may be effective for stroke therapy.

Keywords: Brain repair; Focal ischemic stroke; GDNF; Neuronal protection; Reactive astrocytes.