Tacrolimus (FK506) and cyclosporin A reduce macrophage recruitment to the rat brain injured at perinatal and early postnatal periods.

OBJECTIVE

Tacrolimus (FK506) and cyclosporin A (CsA), immunosuppressants widely used in post-transplantional therapy, have been reported to protect neurons in the injured brain. This effect can be exerted directly and indirectly via inflammatory cells. Since the data come exclusively from studies on the adult brain, we examined effects of the drugs on the macrophage recruitment in the brain injured at early developmental stages.

METHODS

Following the brain injury, 1- and 6-day-old Wistar rats (P1s and P6s, respectively) were treated with FK506 or CsA and injected with [(3)H]thymidine. Brain sections were processed for BSI-B4 isolectin histochemistry and subjected to autoradiography to visualize proliferating and non-proliferating macrophages.

RESULTS

In P1s (n=33), FK506 evoked a dose-dependent reduction in the number of macrophages. P6s (n=30) presented greater decreases in macrophage numbers and their proliferative activity than the newborns. CsA application in P1s (n=27) affected neither recruitment of macrophages to the region of injury nor their proliferation. In CsA-treated P6s (n=28), reduction of the macrophage population and its proliferative activity was also seen but was much smaller than that following FK506 administration.

DISCUSSION

High effectiveness of FK506 in regulation of the inflammatory response and neuroprotection observed in the adult brain can also be considered as a possible indirect determinant of neuronal survival following the brain injury at very early developmental stages.