TY - JOUR
T1 - Glutamate receptor antagonists modulate heat shock protein response in focal brain ischemia
AU - Pettigrew, L. Creed
AU - Holtz, Mary L.
AU - Minger, Stephen L.
AU - Craddock, Susan D.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2003/3
Y1 - 2003/3
N2 - 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 pre-treatment 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.
AB - 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 pre-treatment 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.
KW - Cerebral ischemia
KW - Glia
KW - Glutamate
KW - Heat shock protein
KW - Neuron
KW - Receptor
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U2 - 10.1179/016164103101201201
DO - 10.1179/016164103101201201
M3 - Article
C2 - 12635523
AN - SCOPUS:0037372941
SN - 0161-6412
VL - 25
SP - 201
EP - 207
JO - Neurological Research
JF - Neurological Research
IS - 2
ER -