title: The effect and mechanism of growth hormone replacement on cognitive function in rats with traumatic brain injury.
abstract: OBJECTIVE
  The effects of growth hormone on cognitive dysfunction were observed in a controlled cortical impact (CCI) rat model and the underlying mechanism was explored.
  
  
  METHODS
  Three-month-old male SD rats were randomly divided into sham (n = 10), control (n = 10), and CCI groups (n = 40) The parameters were set as follows: striking speed, 3.5 m/s; impact depth, 1.5 mm; and dwell time, 400 msec. Eight and ten weeks post-injury, the GH levels were measured the water maze test and novel object recognition test were performed. CCI rats were divided into normal and decreased GH groups, and further randomly divided into two sub-groups (rhGH treatment and saline vehicle groups). All rats were tested for SYN, BDNF, and TrkB mRNA in the prefrontal cortex and hippocampus by RT-PCR.
  
  
  RESULTS
  CCI rats 8 weeks post-injury had cognitive dysfunction regardless of the GH level (P<0.05). rhGH treatment improved cognitive function in CCI rats. There was a positive correlation between the expression of prefrontal BDNF and SYN mRNA in CCI rats after rhGH therapy and the water maze test score (r = 0.773 and 0.534, respectively; P<0.05). Furthermore, the expression of BDNF, TrkB, and SYN mRNA in the hippocampus was negatively correlated with the water maze test score (r = 0.602, 0.773, 0.672, and 0.783, respectively; P<0.05). There was a difference in the expression of hippocampal and prefrontal BDNF, TrkB, and SYN mRNA (P<0.05).
  
  
  CONCLUSIONS
  rhGH treatment had a positive effect on cognitive function, which was more evident in GH-deficient rats. The increased expression of hippocampal and prefrontal BDNF and TrkB mRNA is implicated in rhGH therapy to improve cognitive function. Changes in the expression of hippocampal SYN mRNA following rhGH therapy may also play a role in improving cognitive function.
authors.affiliation: China Rehabilitation Research Center, Capital Medical University, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Beijing Jishuitan Hospital, Beijing, China.
authors.forename: Mengqi
authors.initials: M
authors.lastname: Han
authors.affiliation: China Rehabilitation Research Center, Capital Medical University, Beijing, China.
authors.forename: Xiaonian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: China Rehabilitation Research Center, Capital Medical University, Beijing, China.
authors.forename: Xinting
authors.initials: X
authors.lastname: Sun
authors.affiliation: Beijing Xuanwu Hospital, Capital Medical University, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ling
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D005106:Exploratory Behavior / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D016708:Synaptophysin / Q000235:genetics / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D016708:Synaptophysin; C569016:Syp protein, rat; D019382:Human Growth Hormone; D020813:Receptor, trkB