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Abstract
Objective: To investigate mechanisms behind the faster rehabilitation of limb fractures when associated with traumatic brain injury (TBI).
Methods: New Zealand rabbits were divided into TBI group and sham-operation group for four studies as follows: (1) blood and cerebrospinal fluid (CSF) were drawn on days 1, 3, and 7 to demonstrate changes in serum leptin, growth hormone (GH), insulin-like growth factor 1 (IGF-1), and CSF leptin; (2) bone defection was created by drilling in the tibial bone and either leptin or normal saline was injected into rabbit’s cerebellomedullary cistern. X-ray was taken at 1 days, 2 weeks, and 5 weeks and evaluated by criteria to determine rate of bone healing; (3) FITC-labeled rabbit leptin was injected into TBI and sham-operation groups, and frozen sections of rabbit brain were observed to identify differences in central nervous system (CNS) leptin by fluorescence; (4) polymerase chain reaction (PCR) was used to evaluate the expression of leptin production by brain tissue.
Results: Serum and CSF leptin, GH, and IGF-1 concentrations were found to be higher in the TBI group than the sham-operation group at days 1, 3, and 7 (P<0·05). CSF leptin of the TBI group was positively correlated with serum leptin on day 1 (P<0·05), and positively correlated with GH and IGF-1 on days 3 and 7 (P<0·05). X-ray criteria demonstrated that leptin administration caused significantly faster healing calluses at 3 and 5 weeks as compared to control animals (P<0·05). FITC-labeled leptin study demonstrated that TBI animals had stronger expression of leptin in the brain than sham-operated animals. However, PCR of brain tissue leptin showed no significant differences between TBI and sham-operated animals in the expression of leptin.
Conclusions: Our study suggests that increased CSF leptin, likely from blood–brain barrier breakdown, combined with elevated serum GH and IGF-1 after TBI, leads to accelerated fracture healing.
Hua Yan and Hong-Wei Zhang contributed equally to this study. This study was supported by grants from Tianjin Public Health Bureau (Nos. 2011KZ41 and 10KG208) and from Tianjin Municipal Science and Technology Commission (No. 008ZCGYSF01600).