Influence of Neuroprotectants, Cyclosporin A and Tacrolimus, on the Development of Hippocampal Formation in the Rat

Tacrolimus (FK506) and cyclosporin A (CsA) are immunosuppressants that have well-known neuroprotective actions. However, the drugs also have numerous negative neurological side effects observed in clinical practice. The problem of the long-term consequences of the immunosuppressive treatment has never been explored experimentally. Therefore, we focused on the FK506 and CsA influence on the developing hippocampal formation as a region of very high vulnerability to different kinds of damages. Sixand 30-day-old rats (P6s and P30s, respectively) received two injections of FK506 or CsA, at a 24-hr interval. Control rats were injected with a vehicle alone (Cremophor and ethanol mixture). When the rats were 60 days old, quantitative assessments of calretinin(CR+) and parvalbumin-immunopositive (PV+) inhibitory neurons and S-100 protein-immunopositive (S100 +) astrocytes were performed within the hippocampal formation. In comparison to naive rats, vehicle-, FK506or CsA-treated P6s showed no changes in CR+ or PV+ neuronal quantity, but a significant increase in the density of S-100 + astrocytes was noted. Additionally, reduction in the size of the hippocampal formation was recorded following CsA injections performed on P6. In P30s, injections of the vehicle alone and of FK506 but not those of CsA, led to significant reductions of the CR+ neurons. The results suggest similar negative long-term effects of FK506 or CsA on the developing hippocampus. Of particular interest are the negative effects of the vehicle alone.