Neural Regeneration Research ›› 2018, Vol. 13 ›› Issue (12): 2134-2140.doi: 10.4103/1673-5374.241462

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Dynamic changes in growth factor levels over a 7-day period predict the functional outcomes of traumatic brain injury

Shuai Zhou1, 2, 3, 4, 5, Dong-Pei Yin2, 3, 4, 5, Yi Wang2, 3, 4, 5, Ye Tian2, 3, 4, 5, Zeng-Guang Wang2, 3, 4, 5, Jian-Ning Zhang2, 3, 4, 5   

  1. 1 Department of Intensive Care Unit, Tianjin Medical University General Hospital, Tianjin, China
    2 Tianjin Neurological Institute, Tianjin, China
    3 Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China
    4 Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China
    5 Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
  • Received:2018-09-10 Online:2018-12-15 Published:2018-12-15
  • Contact: Zeng-Guang Wang, MD, wzgforrest@163.com; Jian-Ning Zhang, MD, PhD, jianningzhang@hotmail.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81330029 (to JNZ), 81501057 (to YT); the Science & Technology Development Fund of Tianjin Education Commission for Higher Education in China, No. 2016YD02 (to YW); the Technology Program Fund of Tianjin Health and Family Planning Commission for the Key Field of Traditional Chinese Medicine, No. 2018001 (to ZGW).

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Abstract:

Traumatic brain injury (TBI) can result in poor functional outcomes and death, and overall outcomes are varied. Growth factors, such as angiopoietin-1 (Ang-1), vascular endothelial growth factor (VEGF), and granulocyte-colony stimulating factor (G-CSF), play important roles in the neurological functions. This study investigated the relationship between serum growth factor levels and long-term outcomes after TBI. Blood samples from 55 patients were collected at 1, 3 and 7 days after TBI. Blood samples from 39 healthy controls were collected as a control group. Serum Ang-1, G-CSF, and VEGF levels were measured using ELISA. Patients were monitored for 3 months using the Glasgow Outcome Scale-Extended (GOSE). Patients having a GOSE score of > 5 at 3 months were categorized as a good outcome, and patients with a GOSE score of 1–5 were categorized as a bad outcome. Our data demonstrated that TBI patients showed significantly increased growth factor levels within 7 days compared with healthy controls. Serum levels of Ang-1 at 1 and 7 days and G-CSF levels at 7 days were significantly higher in patients with good outcomes than in patients with poor outcomes. VEGF levels at 7 days were remarkably higher in patients with poor outcomes than in patients with good outcomes. Receiver operating characteristic analysis showed that the best cut-off points of serum growth factor levels at 7 days to predict functional outcome were 1,333 pg/mL for VEGF, 447.2 pg/mL for G-CSF, and 90.6 ng/mL for Ang-1. These data suggest that patients with elevated levels of serum Ang-1, G-CSF, and decreased VEGF levels had a better prognosis in the acute phase of TBI (within 7 days). This study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800018251) on September 7, 2018.

Key words: nerve regeneration, traumatic brain injury, vascular endothelial growth factor, angiopoietin-1, granulocyte-colony stimulating factor, outcomes, secondary brain injuries, blood-brain barrier, brain edema, acute phase, clinical trial, neural regeneration