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. (C) 2013 Elsevier B.V. All rights reserved.