Reactive Astrocytes in Acute Stage after Experimental Brain Injury: Relationship to Extravasated Plasma Protein and Expression of Heat Shock Protein

It is well known that an astrocytic response occurs after brain damage; however, the mechanisms initiating this acute astrocytic response remain unclear. In this study, we examined the immunolocalization of glial fibrillary acidic protein (GFAP) to investigate the astrocytic response within 72 h after injury. Further, we related these results to the distribution of extravasated plasma protein and the expression of stress protein. Adult male Wistar rats were subjected to a lateral fluid percussion brain injury. Animals were sacrificed at 1, 6, 24, and 72 h postinjury. Each brain section was inimunostained for GFAP, extravasated albumin, and heat shock protein (HSP 72). Immunoreactive astrocytes, extravasated albumin, and HSP 72 positive cells were evaluated by light microscopy. Reactive astrocytes were defined by the presence of increased immunoreactivity to anti-GFAP. By 6 h, the presence of reactive astrocytes was restricted to the impact site and the hemorrhagic external capsule. At 24 h, reactive astrocytes were identified in the entire injured hemisphere. By 72 h, the immunoreactive astrocytes were more pronounced than at 24 h. At 1 h, extravasated albumin was found at the impact site, the hemorrhagic external capsule, the parasagittal cortex, hippocampus, thalamus, and midbrain. By 72 h, the immunostaining of albumin was more widely distributed. HSP 72 immunoreactive glia were detected only at the impact site and the hemorrhagic external capsule. In summary, the distribution of reactive astrocytes at 6 h was associated with HSP 72-positive glia rather than the extravasation of albumin. In contrast, the distribution of reactive astrocytes at 24 and 72 h paralleled that of extravasated albumin. These results suggest that the initial response of astrocytes is correlated to glial stress and/or injury and that humoral factors play a role in the subsequent responses.