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.