Adrenomedullin Reduces Secondary Injury and Improves Outcome in Rats with Fluid Percussion Brain Injury

作者:Gao, Wei; Ju, Ying-Nan; Chen, Jian-Feng; Zhou, Qiang; Song, Chun-Yu; Wang, Yue-Zhen; Cao, Hong-Ling; Yang, Wan-Chao*
来源:World Neurosurgery, 2018, 119: E765-E773.
DOI:10.1016/j.wneu.2018.07.265

摘要

OBJECTIVE: Traumatic brain injury (TBI) is a devastating neurologic injury and remains a major cause of death in the world. Secondary injury after TBI is associated with long-term disability in patients with TBI. This study evaluated adrenomedullin (AM) on secondary injury and neurologic functional outcome in rats after TBI. METHODS: Forty-eight Sprague Dawley rats were randomly assigned into 3 groups: sham, TBI, and TBI with AM groups. TBI was induced by fluid percussion injury, and AM was intravenously injected. Neurologic function was examined at 2, 3, and 7 days after TBI. Enzyme-linked immunosorbent assay was used to test tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-8 levels in the brain. Brain edema and bloodebrain barrier (BBB) permeability in brain tissue were tested. Western blot was used to examine the expression of aquaporin-4, phosphorylated myosin lightchain, and cleaved caspase-3. Terminal deoxynucleotidyl transferase dUTP nick end labeling was used to test the apoptosis. RESULTS: Compared with the sham group, TNF-alpha, IL-1 beta, and IL-6 levels, brain edema, BBB permeability, neurologic examination scores, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells, and expression of aquaporin-4, phosphorylated myosin light-chain, and cleaved caspase-3 significantly increased in the TBI group. AM treatment significantly inhibited TBI-induced effects. CONCLUSIONS: AM can improve neurologic function and ameliorate brain injury in rats with TBI. AM exerts its neuroprotective effect via its anti-inflammatory and antiapoptotic effect.