Neurons and glia reacting to ischemic injury exhibit delayed expression of
heat shock proteins (HSPs). We tested the hypothesis that
glutamate receptor antagonists alter neuronal and glial activation during focal
cerebral ischemia, as shown by spatio-temporal changes in HSP immunoreactivity. Rats underwent focal
ischemia by permanent occlusion of the middle cerebral artery. All animals were pre-treated with
NBQX (30 mg kg-1), a competitive antagonist of the
AMPA/
kainate receptor, or
CGS-19755 (10 mg kg-1), a competitive
NMDA receptor antagonist, and euthanatized after 6 or 24 h of
ischemia to demonstrate regional immunoreactivity of HSP-72 or 32 in brain. Neurons immunolabeled for HSP-72 appeared in the penumbral region adjacent to the
infarct at 24 h and increased in number and distribution after pretreatment with
NBQX or
CGS-19755. Immunolabeling for HSP-32 revealed that pre-treatment with
CGS-19755 caused ramified glia to infiltrate the ischemic cortex at 6 h, a pattern that was not seen in ischemic controls until 24 h. Blockade of the
NMDA or
AMPA/
kainate receptor modulates cellular stress responses in both neurons and glia within the developing
infarct. We conclude that early, rather than delayed, expression of HSP-32 is a sensitive
indicator of glial activation induced specifically by
CGS-19755.