Astrogliosis

Abstract

In addition to their many functions in the healthy central nervous system (CNS), astrocytes respond to CNS damage and disease through a process called astrogliosis. For many decades, astrogliosis was sparsely studied and enigmatic. This article examines recent evidence supporting a definition of astrogliosis as a spectrum of heterogeneous potential changes in astrocytes that occur in a context-specific manner as determined by diverse signaling events that vary with the nature and severity of different CNS insults. Astrogliosis is associated with essential beneficial functions, but under specific circumstances can lead to harmful effects. Potential dysfunctions of astrocytes and astrogliosis are being identified that can contribute to, or be primary causes of, CNS disorders, leading to the notion of astrocytopathies. A conceptual framework is presented that allows consideration of normally occurring and dysfunctional astrogliosis and their different roles in CNS disorders.

Figure 1.

Reactive astrocytes receive and send diverse molecular instructions. Schematic drawings depict examples of diverse molecular signals that instruct reactive astrocytes (A), or that reactive astrocytes release to instruct other cells (B). For abbreviations, see Table 1.

Figure 2.

Schema of astrogliosis gradient from mild to moderate to scar. In healthy CNS tissue, many astrocytes do not express detectable levels of the cytoskeletal protein, GFAP. In mild to moderate astrogliosis, most astrocytes up-regulate GFAP and hypertrophy their cytoskeleton but preserve individual domains. In severe diffuse astrogliosis, there is also proliferation (depicted by red nuclei). Compact astroglial scars are comprised of newly proliferated astrocytes with densely overlapping processes that form borders to damaged tissue and inflammation.

Figure 3.

Schema that distinguishes normal from abnormal astrogliosis and depicts different pathways that can lead to astrocytopathies.