Assessments of Reactive Astrogliosis Following CNS Injuries

The term “gliosis” is generally defined as the cellular process by which glial cells in the CNS respond to insult and is used to describe the functional, morphological, biochemical, and molecular changes that occur in response to injury or disease. However, gliosis is most associated with the activation of astrocytes in response to CNS insults and is therefore discussed here as reactive astrogliosis. Although the molecular, biochemical, and functional changes associated with reactive astrogliosis are not fully elucidated, the morphological changes are better described. One morphological hallmark is the up-regulation of the intermediate filament protein glial fibrillary acidic protein (GFAP) which is often accompanied by a thickening of the main astrocyte processes, or hypertrophy. In healthy tissue, GFAP is the main intermediate filament expressed and the expression depends upon the subpopulation of astrocytes examined. After CNS injury, the expression of GFAP is significantly increased albeit heterogeneity and regional differences remain. It is important to note that in both nonreactive and reactive astrocytes, the expression of GFAP protein that can be detected by immunohistochemistry (IHC) is limited to the proximal portions of cell processes which means that the complexity of the fine distal processes and their associated volume cannot be visualized with GFAP-IHC. Techniques for evaluating GFAP-IHC in brain and spinal cord tissue from rodents are discussed.