Potential role of fibronectin in microglia/macrophage activation following cryoinjury in the rat brain: an immunohistochemical study.

To investigate whether fibronectin, a high-molecular weight glycoprotein of the extracellular matrix (ECM), plays a role in the activation of microglia/macrophages after brain injury, we examined the changes in fibronectin and arginase-1, a marker for alternatively activated macrophages, in a rat cryoinjury model using Western blot analysis, real-time reverse transcription PCR and immunohistochemistry. The protein and mRNA level of fibronectin and arginase-1 significantly increased in the injury site of the ipsilateral cerebral cortex at days 4 and 7 after cryoinjury but was decreased at day 14. The immunohistochemical analysis revealed fibronectin expression in ED1-positive microglia/macrophages and reactive astrocytes, in the lesion core and periphery, respectively. Fibronectin immunoreactivity in the lesion was similar to arginase-1 except that fibronectin was detected in the ECM after cryoinjury. The present results suggest that fibronectin was extravasated into injured brain lesions via an impaired blood-brain barrier and stimulated glial cells including microglia and infiltrating macrophages in the lesion core and periphery to become alternatively activated microglia/macrophages, which modulated CNS inflammation after brain injury.