ERK/MAP kinase is chronically activated in human reactive astrocytes

REACTIVE astrogliosis is the most prominent macroglial response to diverse forms of CNS injury. We assessed a potential role for the extracellular sig nal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway be cause it represents a common effector for several major families of transme mbrane receptors implicated in astrogliosis. Immunohistochemical detection of activated ERK/MAPK in a series of human neurosurgical specimens utilizin g phosphorylation state-dependent antibodies consistently revealed intense immunoreactivity in reactive astrocytes in both subacute and chronic lesion s, including infarct, mechanical trauma, chronic epilepsy, and progressive multifocal leukoencephalopathy. Neurons, oligodendroglia, and most inflamma tory cells showed little or no detectable activation. These observations su ggest a testable hypothesis: activation of the ERK/MAPK pathway is an oblig atory step for the triggering and/or persistence of reactive astrogliosis. (C) 1999 Lippincott Williams & Wilkins.