The Astrocyte Response to Neural Injury: A Review and Reconsideration of Key Features

Details

• Personal Author:
  Little AR ; O'Callaghan JP
• Description:
  Over the last twenty years, considerable evidence has accumulated to suggest that gliosis represents a homotypic reponse of astrocytes and microglia to all types of nervous system injury, including damage resulting from exposure to chemicals or chemical mixtures. The astrocytic component of this response, often referred to as "reactive" gliosis or astrogliosis, has received the most attention and is the subject of numerous reviews (Martin and O'Callaghan, 1996; Kimelberg and Norenberg, 1994; Norenberg, 1994; Eng and Ghirnikar, 1994; Nortan et al., 1992; Perry and Andersson, 1992; Eng et al., 1992; Kimelberg and Norenberg, 1989; Nalhotra et al., 1990; Eng, 1988a; Eng and DeArmond, 1981). Most of the progress in characterizing reactive gliosis over the years can be traced to the discovery of GFAP, the major protein of astrocyte intermediate filaments (Eng, 1988b; Eng, 1985; Eng et al., 1985). Astrocytes accumulate intermediate filaments when they become reactive (Eng, 1988b; Eng, 1987; Brock and O-Callaghan, 19987; Aono et al., 1985; Smith et al., 1984; Amaducci et al., 1981), therefore, by definition, reactive astrocytes show an enhanced expression of GFAP. Immunohistochemistry of GFAP has been widely utilized to monitor astrocytic responses to neural injury and has firmly established GFAP as the key biomarker of reactive gliosis. Although less prevalent in the literature, GFAP analysis by immunoblot and immunoassay also has been used to establish, quantitatively, the features of reactive gliosis (Norton et al., 1992; Aono et al., 1985; O'Callaghan, 1993; O'Callaghan et al., 1995). We have used the latter approach to document regional differences in GFAP expression and the utility of GFAP as a marker of the does-, time-, and region-dependent damage resulting from exposure to broad classes of known and suspected neurotoxic agents. Our purpose here is not to revisit these topics, but rather, it is to review and challenge some commonly held views on the nature of the astrocyte response to CNS injury. Specifically we will discuss the potential role of GFAP in gliosis, conflicting data obtained from in vitro vs. in vivo analysis of "reactive" astrocytes, and the relative contribution of hypertrophy and hyperplasia to reactive gliosis. Because descriptions of cytokine and hormonal regulation of astroglial responses pervade the in vitro and in vivo literature, cytokine and hormonal effectors will be discussed as they relate to each feature of gliosis. Gliosis in the developing nervous system also will be examined along with the merits of analysis of gliosis by GFAP immunochistochemistry vs. GFAP immunoassay. Understanding the features of the astroglial response to injury is critical for the accurate use of GFAP as a biomarker for detecting and quantifying neurotoxicity and for designing effective strategies for neuroprotection or neurotrophic support following neurotoxic exposures. [Description provided by NIOSH]
• Subjects:
  Immune System Nervous System Nervous System Diseases Occupational Health Safety
• Keywords:
  Immunochemistry In-vitro-studies In-vivo-studies Nervous-system-disorders Neurotoxic-effects Neurotoxicity
• ISBN:
  0415273463
• Publisher:
  Taylor and Francis
• Document Type:
  Text
• Genre:
  Book
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  233-265
• NIOSHTIC Number:
  nn:20023238
• Citation:
  Site-selective neurotoxicity. Lester DS, Slikker W Jr., Lazarovici P, eds. New York: Taylor and Francis, 2002 Feb; :233-265
• Editor(s):
  Lester DS; Slikker W Jr.; Lazarovici P
• Federal Fiscal Year:
  2002
• Peer Reviewed:
  False
• Source Full Name:
  Site-selective neurotoxicity
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b028351c2d95cb1541329358afa32ace2a02dd612ac9c2dbb78ab15f4db854f0ca18ea5234e1382e1a7ee503180f441ab0c72c08a19acd2c4cf7ae392652d127
• Download URL:
  https://stacks.cdc.gov/view/cdc/195774/cdc_195774_DS1.pdf
• File Type:
  [PDF - 4.69 MB ]