Tacrolimus (FK506) increases neuronal expression of GAP-43 and improves functional recovery after spinal cord injury in rats

Tacrolimus (FK506), a widely used immunosuppressant drug, has neurite-promo ting activity in cultured PC12 cells and peripheral neurons. The present st udy investigated whether tacrolimus affects the expression of the neuronal growth-associated protein, GAP-43, as well as functional recovery after pho tothrombotic spinal cord injury in the rat. In injured animals receiving ta crolimus, the number of neurons expressing GAP-43 mRNA and protein approxim ately doubled compared to that in injured animals receiving vehicle alone. This increase in GAP-BE-positive cells was paralleled by a significant impr ovement in neurological function evaluated by open-field and inclined plane tests. Another FKBP-18 ligand (V-10,367) had similar effects on GAP-43 exp ression and functional outcome, indicating that the observed effects of tac rolimus do not involve inhibition of the phosphatase calcineurin. Thus, tac rolimus, a drug which is already approved for use in humans, as well as oth er FKBP-12 ligands which do not inhibit calcineurin, could potentially enha nce functional outcome after CNS injury in humans. (C) 1998 Academic Press.