EPIDERMAL GROWTH-FACTOR RECEPTOR IN PROLIFERATING REACTIVE GLIA FOLLOWING TRANSIENT FOCAL ISCHEMIA IN THE RAT-BRAIN

Severe transient focal cerebral ischemia causes brain infarction with a strong glial reaction. We have studied whether postischemic reactive glial cells express epidermal growth factor receptor (EGFR) following middle cerebral artery occlusion in the rat. We have also looked for signs of proliferating activity, as EGFR is know to be involved in cel l growth and proliferation in certain non-neural cells. EGFR was studi ed using three different antibodies which were found to stain for a ty rosine-phosphorylated protein (p170) corresponding to the membrane-anc hored EGFR. Neurons of the control brain were strongly immunoreactive to EGFR, but a decrease of EGFR-immunoreactivity was seen in the ipsil ateral brain side from 24 h postischemia due to neuronal loss. However , the presence of abundant glial cells strongly immunoreactive to EGFR became apparent in this area from 4 days postischemia onward. The use of microglial (lectin or OX-42) and astroglial (GFAP) markers showed that these postischemic EGFR-stained cells were reactive microglia/mac rophages and astroglia. The subcellular localization of EGFR in reacti ve microglia/macrophages was compatible with the network of the Golgi apparatus, as revealed with an antibody against a peripheral membrane- bound protein of the Golgi. The presence of abundant proliferating cel ls in the ischemic brain was detected from 4 days postischemia with an antibody against proliferating cell nuclear antigen. Proliferating re active microglia/macrophages were abundant within the infarcted brain side, whereas proliferating astrocytes were found mainly in the immedi ate periphery of the infarct limiting the necrotic area from the undam aged tissue. These proliferating cells were immunoreactive to EGFR. Th e results show the presence of EGFR in postischemic reactive glial cel ls and suggest that EGFR-dependent pathways mediate signal transductio n in reactive glia following transient focal cerebral ischemia. (C) 19 98 Wiley-Liss, Inc.