Abstract
ObjectiveThe effects of growth hormone on cognitive dysfunction were observed in a controlled cortical impact (CCI) rat model and the underlying mechanism was explored.MethodThree-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.ResultsCCI 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)ConclusionrhGH 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.
Highlights
Traumatic brain injury (TBI) is a medical condition with high morbidity worldwide, and leading mortality and disability rates [1]
There was a positive correlation between the expression of prefrontal Brain-derived neurotrophic factor (BDNF) and SYN mRNA in cortical impact (CCI) rats after recombinant human growth hormone (rhGH) therapy and the water maze test score (r = 0.773 and 0.534, respectively; P,0.05)
Conclusion: rhGH treatment had a positive effect on cognitive function, which was more evident in growth hormone (GH)-deficient rats
Summary
Traumatic brain injury (TBI) is a medical condition with high morbidity worldwide, and leading mortality and disability rates [1]. Cognitive impairment is one of the most common symptoms in patients with moderate-to-severe TBI. Patients with varying degrees of TBI may develop cognitive impairment, causing a significant impact on daily life, which impedes a patient returning to society. Endocrine dysfunction after a TBI may be due to primary or secondary lesions in the hypothalamus and pituitary. Any degree of TBI can cause varying changes in pituitary hormone levels [2], the most prominent of which is growth hormone (GH) deficiency. GH is important to the development of the central nervous system, especially in promoting the maturation of the brain, myelin formation, glial cell differentiation, and cognitive function. The relationship between the GH level and cognitive function has been studied in Alzheimer’s disease (AD)
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