Ultrastructural and immunocytochemical studies of macrophages in an excitotoxin induced lesion in the rat brain

Abstract

An epidural application of kainic acid (KA) over the cerebral cortex in rat resulted in an extensive lesion in the ipsilateral cerebral cortex. This procedure elicited an accumulation of a large number of macrophages at the site of lesion covering a period of 4 weeks beginning 4 days after the KA application. The macrophages in the centre of lesion were characterized by abundant cytoplasm containing a variable number of lysosomes and phagosomes. Neurons at the same site were depleted during the period examined. They underwent degeneration following the KA treatment. With the monoclonal antibodies OX-42, OX-18 and OX-6, intense immunoreactivity was observed in these cells at the light and electron microscopic levels. Besides these antibodies, the cells were stained positively with the isolectin Griffonia simplicifolia (GSAI-B4). At the periphery of the lesion, many cells bearing the external morphology of microglia were also intensely stained with the GSAI-B4 and the monoclonal antibodies. It was concluded from this study that neuronal degeneration, caused by the excitotoxin KA, induced the accumulation of macrophages which exhibited CR3 receptors (marked by OX-42), MHC I antigen (marked by OX-18) and MHC Ia (marked by OX-6). The expression of these surface antigens may be related to their active phagocytic activity. The reaction with GSAI-B4 indicates the presence of specific lectin receptors on the macrophages which would serve a similar function. The present lectin histochemistry and immunohistochemical studies suggest that macrophages in the centre of the KA-induced lesion were derived from infiltrated monocytes while those at the periphery originated from the activation of local microglial cells.