Abstract OBJECTIVE: Immunosuppressant tacrolimus (FK506) has shown neuroprotective effects on hypoxic-ischemic brain damage (HIBD) in the adult animal model. This study investigated whether FK506 has a protection against HIBD in neonatal rats by examining growth-associated protein-43 (GAP-43) expression in the hippocampus. METHODS: Ninety-six seven-day-old Sprague-Dawley rats were randomly divided into three groups: sham-operation, HIBD and FK506 intervention group. HIBD was induced in the later two groups. The FK506 intervention group was intraperitoneally injected with FK506 immediately after HIBD, at a dosage of 1 mg/kg daily, for three days. The HIBD group was injected with normal saline. Immunohistochemical technical was applied to examine GAP-43 expression in the hippocampus 24 and 72 hrs and 7 and 14 days after HIBD. RESULTS: Compared with the HIBD group, hematoxylin-eosin staining showed attenuated neuronal necrosis in the FK506 intervention group. In the HIBD group, the expression of GAP-43 increased significantly 72 hrs, and 7 and 14 days after HIBD compared with that in the sham-operation group. The GAP-43 expression in the FK506 intervention group was significantly higher than that in the HIBD group 72 hrs and 7 days after HIBD. CONCLUSIONS: FK506 might have neuroprotective effects against HIBD in neonatal rats.［Chin J Contemp Pediatr, 2009, 11 (1):65-68］
ZHOU Yan,XIONG Ying,YUAN San-Ying. Effect of tacrolimus on growth-associated protein-43 expression in the hippocampus of neonatal rats with hypoxic-ischemic brain damage[J]. 中国当代儿科杂志, 2009, 11(01): 65-68.
ZHOU Yan,XIONG Ying,YUAN San-Ying. Effect of tacrolimus on growth-associated protein-43 expression in the hippocampus of neonatal rats with hypoxic-ischemic brain damage[J]. CJCP, 2009, 11(01): 65-68.
［1］Furuichi Y, Katsuta K, Maeda M, Ueyama N, Moriquchi A, Matsuoka N, et al. Neuroprotective action of tacrolimus (FK506) in focal and global cerebral ischemia in rodents: dose dependency, therapeutic time window and long-term efficacy［J］. Brain Res, 2003, 965(1-2): 137-145.
［2］Macleod MR, O′Collins T, Horky LL, Howells DW, Donnan GA. Systematic review and metaanalysis of the efficacy of FK506 in experimental stroke［J］. J Cereb Blood Flow Metab, 2005, 25(6): 713-721.
［3］Gordon T, Sulaiman O, Boyd JG. Experimental strategies to promote functional recovery after peripheral nerve injuries［J］. J Peripheral Nerv Syst, 2003, 8(4): 236-250.
［4］Aigner L, Arber S, Kapfhammer JP, Laux T, Schneider C, Botteri F, et al. Overexpression of the neural growth-associated protein GAP-43 induces nerve sprouting in the adult nervous system of transgenic mice［J］. Cell, 1995, 83(2): 269-278.
［5］Strittmatter SM, Fankhauser C, Huang PL, Mashimo H, Fishman MC. Neuronal pathfinding is abnormal in mice lacking the neuronal growth cone protein GAP-43［J］. Cell, 1995, 80(3): 445-452.
［6］Sharkey J, Butcher SP. Immunophilins mediate the neuroprotective effects of FK506 in focal cerebral ischaemia［J］.Nature, 1994, 371(6495): 336-339.
［9］Farina V, Gadau S, Lepore G, Manca P, Zedda M. Growth-associated protein expression in the frontal and occipital cortices of callosotomized rats［J］. Funct Neurol, 2004, 19(3):181-184.
［10］Madsen JR, MacDonald P, Irwin N, Goldberg DE, Yao GL, Merir KF, et al. Tarcrolimus (FK506) increases neuronal expression of GAP-43 and improves functional recovery after spinal cord injury in rats［J］. Exp Neurol, 1998, 154(2): 673-683.
［12］Li F, Omori N, Hayashi T, Jin G, Sato K, Nagano I, et al. Protection against ischemic brain damage in rats by immunophilin ligand GPI-1046［J］. J Neurosci Res, 2004, 76(3): 383-389.
