Characterization and manipulation of the reactive astrocyte response following axotomy-induced motoneuronal injury and death

Axotomy induced target deprivation in immature animals results in significant neuronal cell death, in contrast to the low levels of death in adult animals. This death is accompanied by reactive astrocytic changes, characterized by increases in the intermediate filament, glial fibrillary acidic protein (GFAP). We examined the time-course for axotomized immature rat facial motoneuron (FMn) death and the accompanying changes in the reactive astrogliosis. ({dollar}-{dollar})-Deprenyl, an agent previously shown to decrease the death of axotomized immature FMns, was studied to determine if it could alter the time-course of FMn death and modulate the accompanying reactive gliosis. Both reactive astrocyte hypertrophy and GFAP immunodensity were found to increase 1 day post axotomy (DPA), increase maximally by 7 DPA, with both indices declining thereafter. ({dollar}-{dollar})-Deprenyl increased both indices of GFAP immunoreactivity above saline control values at 1 and 3 DPA but attenuated the GFAP immunoreactivity at later DPAs. From somal counts, the majority (75%) of axotomy induced FMn death was completed by 7 DPA, and ({dollar}-{dollar})-deprenyl treatment shifted the FMn loss by 24-48 hours and increased survival.; In order to assess the role of reactive astrogliosis and whether the presence of nearby astrocytes contributed to the survival of FMns, astrocytes were regionally ablated with the gliotoxin L-{dollar}alpha{dollar}-aminoadipic acid. Following axotomy we found that there was only minimal death of adult FMns. However, by 7 days but not 3 days there was a significant (p = 0.047) loss of FMns in sections near the area of gliotoxin injection, and the death was further increased in axotomized FMns (p = 0.007). These results suggest that astrocytes contribute to the survival of normal unaxotomized FMns and that their role may be of even greater importance following axotomy.