Fibrotic Scar in Neurodegenerative Diseases

Abstract

The process of uncontrolled internal scarring, called fibrosis, is now emerging as a pathological feature shared by both peripheral and central nervous system diseases. In the CNS, damaged neurons are not replaced by tissue regeneration, and scar-forming cells such as endothelial cells, inflammatory immune cells, stromal fibroblasts, and astrocytes can persist chronically in brain and spinal cord lesions. Although this process was extensively described in acute CNS damages, novel evidence indicates the involvement of a fibrotic reaction in chronic CNS injuries as those occurring during neurodegenerative diseases, where inflammation and fibrosis fuel degeneration. In this mini review, we discuss recent advances around the role of fibrotic scar formation and function in different neurodegenerative conditions, particularly focusing on the rising role of scarring in the pathogenesis of amyotrophic lateral sclerosis, multiple sclerosis, and Alzheimer's disease and highlighting the therapeutic relevance of targeting fibrotic scarring to slow and reverse neurodegeneration.

Keywords: Alzheimer's disease; amyotrophic lateral sclerosis; astrocytes; fibroblasts; microglia; multiple sclerosis.

Figure 1

Fibrotic and glial scar in ALS mice. (A) Representative confocal images of lumbar spinal cord sections from non-transgenic (Ntg) and hFUS (ALS) mice at end stage of the disease. ALS section displays abundant vimentin-immunoreactive cells (blue) and glial fibrillary acidic protein (GFAP)-immunoreactive astroglial cells organized in a scar-like fashion (red). Scale bar = 20 μm. A higher magnification of the area marked by the white square is shown on the right and displays cells stained by both vimentin and GFAP in the gray matter (GM) and vimentin-positive cells closely associated to GFAP-positive astrocytes in the white matter (WM) Scale bar = 100 μm. (B) Representative confocal images of lumbar spinal cord sections from non-transgenic (Ntg) and hFUS (ALS) mice at end stage of the disease. ALS section displays an increase in α-smooth muscle actin (α-SMA)-immunoreactive cells (green) closely surrounded by GFAP-positive cells (red). Scale bar = 100 μm.