GLIAL CHANGES FOLLOWING AN EXCITOTOXIC LESION IN THE CNS .2. ASTROCYTES

Astrocytes are involved, as are microglia/macrophages [Marty et al. (1991) Neuroscience 45, 529-539], in the formation of a glial scar after CNS lesions. This study was undertaken to follow the time-course of changes in the morphology and distribution of astrocytes that takes place during the formation of a glial scar after kainic acid injection in the rat thalamus. The astrocytes were identified using an antibody raised against glial fibrillary acidic protein (GFAP) and the progression of their reaction to the lesion was followed from 24 h to one year after the kainate injection. Three periods could be distinguished during the evolution of the astrocytic response in the neuron-depleted area. There was an initial appearance of a large number of GFAP+ cells. These cells displayed profound morphological differences from the normal. They were enlarged, round and devoid of processes. These GFAP+ astrocytes disappeared four days after the lesion. This increase of the GFAP+ cells in the neuron-depleted area may be due to cytoskeletal changes and thus an increased exposure of antigenic sites. In a second period between four and 14 days, the only GFAP+ elements present in the neuron-depleted area were long and straight processes. These processes entered the lesioned area from the periphery and seemed to follow axon bundles. Additionally, during the first weeks, the number of reactive astrocytes increased in a small band just around the area of neuronal loss. The third period began after two weeks. The lesioned area became gradually occupied by GFAP+ astrocytes. These astrocytes were of two types. The first type had the morphology of reactive astrocytes; they were located first at the periphery then progressively in more central zones, and seemed associated with blood vessels, suggesting an inward migration of cells from surrounding areas. The second type was small and appeared simultaneously throughout the area of neuronal loss, suggesting GFAP expression in previously silent astrocytes. These cells could be derived from precursors existing in the adult CNS. The astrocytes were the predominant element in the neuron-depleted area after one month. They became further hypertrophied and formed a dense network over the following months. In summary, reactive astrocytes increase in number during the first month in an area depleted of neurons by an excitotoxin. During this first period microglia/macrophages are, however, the predominant cell population and it is only after the first month that astrocytes form the classical glial scar.