MICROGLIAL AND ASTROGLIAL REACTIONS TO ANTEROGRADE AXONAL DEGENERATION - A HISTOCHEMICAL AND IMMUNOCYTOCHEMICAL STUDY OF THE ADULT-RAT FASCIA-DENTATA AFTER ENTORHINAL PERFORANT PATH LESIONS

The reaction of microglial and a stroglial cells to anterograde axonal degeneration was studied in the fascia dentata of adult rats at vario us timepoints after removal of the entorhinal perforant path projectio n. Microglial cells were identified by histochemical staining for nucl eoside diphosphatase (NDPase) at light and electron microscopical leve ls. Astroglial cells were stained immunocytochemically for glial fibri llary acidic protein (GFAP). Activated astroglial cells and some micro glial cells also stained immunocytochemically for the intermediate fil ament protein vimentin. Phagocytotic activity was detected by histoche mical staining for acid phosphatase. The postlesional connective reorg anization of the cholinergic septohippocampal projection was monitored by histochemical staining for acetylcholinesterase. Twenty-four hours after entorhinal cortex ablation, microglial cells in the perforant p ath zones of the fascia dentata and the adjacent neuropil reacted by s hortening and coarsening of processes and an increase in NDPase reacti vity. These changes occurred prior to a noticeable increase in GFAP im munoreactivity and hypertrophy of astroglial cells (first evident on p ostlesional day 2) or sprouting of cholinergic septohippocampal fibres (first evident on day 3). There was evidence of an early, local proli feration of microglial cells in the denervated perforant path zones an d migration into these zones of microglial cells from adjacent intact areas. The specific accumulation of strongly stained microglial cells within the denervated parts of the dentate molecular layer persisted f or at least 4 weeks, while the astroglial reaction subsided at 3 weeks . The results demonstrate an early activation of microglial cells by a xonal degeneration, and indicate that these cells may play a pivotal, inductive role in the subsequent glial and neural events.