title: Leptin's effect on accelerated fracture healing after traumatic brain injury.
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.
authors.affiliation: Department of Neurosurgery, Tianjin Huanhu Hospital, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yan
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Zhang
authors.forename: Paul
authors.initials: P
authors.lastname: Fu
authors.forename: Bao-Long
authors.initials: BL
authors.lastname: Liu
authors.forename: Wen-Zhe
authors.initials: WZ
authors.lastname: Jin
authors.forename: Shi-Bo
authors.initials: SB
authors.lastname: Duan
authors.forename: Jing
authors.initials: J
authors.lastname: Xue
authors.forename: Kui
authors.initials: K
authors.lastname: Liu
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Sun
authors.forename: Xian-Wei
authors.initials: XW
authors.lastname: Zeng
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D001930:Brain Injuries / Q000097:blood / Q000134:cerebrospinal fluid / Q000150:complications*; D017102:Fracture Healing / Q000187:drug effects*; D013006:Growth Hormone / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020738:Leptin / Q000097:blood / Q000134:cerebrospinal fluid / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D011817:Rabbits; D013978:Tibial Fractures / Q000097:blood / Q000134:cerebrospinal fluid / Q000150:complications* / Q000188:drug therapy*
chemical_list: D020738:Leptin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone