Entorhinal cortex lesion in adult rats induces the expression of the neuronal chondroitin sulfate proteoglycan neurocan in reactive astrocytes

The chondroitin sulfate proteoglycan neurocan is a major component of brain extracellular matrix during development. Neurocan is primarily synthesized by neurons and has the ability to interact with cell adhesion molecules in volved in the regulation of cell migration and axonal growth. Within the fi rst weeks postnatally, neurocan expression is strongly downregulated. To te st whether neurocan is reexpressed in areas of axonal growth (sprouting) af ter brain injury, the time course of neurocan expression was analyzed in th e denervated fascia dentata of the rat after entorhinal cortex lesion (12 h r; 1, 2, 4, and 10 d; 2 and 4 weeks; and 6 months after lesion). In the den ervated zone, immunohistochemistry revealed neurocan-positive astrocytes by 2 d after lesion and a diffuse labeling of the extracellular matrix at all later time points. Electron microscopy confirmed the deposition of neuroca n in the extracellular matrix compartment. In situ hybridization demonstrat ed a strong upregulation of neurocan mRNA within the denervated outer molec ular layer 1 and 4 d after lesion. The combination of in situ hybridization with immunohistochemistry for glial fibrillary acidic protein demonstrated that the neurocan mRNA-expressing cells are astrocytes. These data demonst rate that neurocan is reexpressed in the injured brain. In contrast to the situation during development, astrocytes, but not neurons, express neurocan and enrich the extracellular matrix with this molecule. Similar to the sit uation during development, neurocan is expressed in an area of active axon growth, and it is suggested that neurocan acts to maintain the boundaries o f the denervated fascia dentata after entorhinal cortex lesion.