Extensive and long‐lasting changes of glial cells following transection of the poscommissural fornix in the adult rat

Abstract

Injury to the adult brain results in the formation of a glial scar that involves both activated astroglia and microglia/macrophages. Although reactive gliosis has been linked to failure of axonal regeneration in the adult mammalian CNS, the spatio-temporal pattern of the postlesion responses in morphology and distribution of the major cellular constituents of the gliosis has attracted little attention. In an attempt to define these relationships, we have undertaken a systematic study of astrocytic and microglial/macrophagic responses after stereotactic transection of the postcommissural fornix in rat. To visualize astrocytes, microglia, and macrophages, antibodies against glial fibrillary acidic protein (GFAP), vimentin (VIM), complement receptor type 3 (OX42), and ED1 were used. The cellular responses occurring between 2 h and 1 year postlesion (PL) at various distances distal and proximal to the lesion site were studied. Transection of the postcommissural fornix leads to: 1) a very early microglial reaction both distal and proximal to the lesion, as indicated by OX42-immunoreactivity, followed by a massive astrocytic response; 2) a transient GFAP(-) but VIM(+) region around the lesion center; 3) the appearance of numerous ED1(+) macrophages at PL3d; and 4) long-lasting (at least 1 year) persistence of both astrocytes and microglia/macrophages. The timing and extension of the sequential glial reactions after postcommissural fornix transection are discussed in relation to the myelin degradation and spontaneous sprouting of injured axons that have previously been observed in this lesion model (Wunderlich et al: Glia 10:49-58, 1994).