The chondroitin sulphate proteoglycan brevican is upregulated by astrocytes after entorhinal cortex lesions in adult rats

The chondroitin sulphate proteoglycan brevican is one of the most abundant extracellular matrix molecules in the adult rat brain. It is primarily synt hesized by astrocytes and is believed to influence astroglial motility duri ng development and under certain pathological conditions. In order to study a potential role of brevican in the glial reaction after brain injury, its expression was analysed following entorhinal cortex lesion in rats (12 h, 1, 2, 4, 10, 14 and 28 days and 6 months post lesion). In situ hybridizatio n and immunohistochemistry were employed to study brevican mRNA and protein , respectively, in the denervated outer molecular layer of the fascia denta ta and at the lesion site. In both regions brevican mRNA was upregulated be tween 1 and 4 days post lesion. The combination of in situ hybridization wi th immunohistochemistry for glial fibrillary acidic protein demonstrated th at many brevican mRNA-expressing cells are astrocytes. In the denervated zo ne of the fascia dentata, immunostaining for brevican was increased by 4 da ys, reached a maximum by 4 weeks and remained detectable up to 6 months pos t lesion. Electron microscopic immunocytochemistry showed that brevican is a component of the extracellular matrix compartment. At the lesion site a s imilar time course of brevican upregulation was observed. These data demons trate that brevican is upregulated in areas of brain damage as well as in a reas denervated by a lesion. They suggest a role of brevican in reactive gl iosis and are compatible with the hypothesis that brevican is involved in t he synaptic reorganization of denervated brain areas.