title: Early expression of serum neutrophil gelatinase-associated lipocalin (NGAL) is associated with neurological severity immediately after traumatic brain injury.
abstract: OBJECTIVE
  Intracranial bleeding and inflammatory reactions are common consequences of traumatic brain injury (TBI). Neutrophil gelatinase-associated lipocalin (NGAL), an iron-handling and acute phase protein, may participate in the pathogenesis of TBI. Therefore, we hypothesize that NGAL may be of high diagnostic and therapeutic relevance in the prognosis of TBI.
  
  
  METHODS
  74 subjects were recruited in this study. 30 TBI patients receiving emergent operation were designated as severe TBI group (sTBI), 24 TBI patients receiving conservative treatment as mild TBI group (mTBI), while 20 age-matched healthy volunteers as healthy controls (CNT). We detected the expression and localization of NGAL in brain tissue by Q-PCR, western blotting, and immunofluorescence. Serum NGAL was evaluated by ELISA. Clinical manifestations and outcomes were measured by Glasgow Score (GCS), Trauma score (TS), Revised Trauma score (RTS), APACHEII, Sequential Organ Failure Assessment (SOFA), and Abbreviated Injury Scale (AIS) 85 at admission. Glasgow outcome score (GOS) and Karnofsky Performance Score (KPS) were documented at discharge.
  
  
  RESULTS
  NGAL mRNA and protein levels in brain tissue from sTBI group were profoundly higher than control tissue. Double labeled NGAL with GFAP, NeuN and Iba-1 by immunofluroscence demonstrated that increased NGAL was mainly located in neurons. Compared to CNT and mTBI groups, serum NGAL were significantly increased in sTBI group (sTBI: 532.6±71.77ng/ml vs. mTBI: 230.5±29.59ng/ml, p<0.01; sTBI: 532.6±71.77ng/ml vs. CNT 178.0±19.83ng/ml, p<0.01). Linear regression analysis indicated that there was a negative correlation between the NGAL levels and GCS (r=-0.427, p=0.033), TS (r=-0.429, p=0.032), RTS (r=-0.413, p=0.040) in sTBI group. However, NGAL levels did not correlated with GOS and KPS scores. The NAGL cut-off value of 244.13ng/ml yielded good sensitivity at 84% and specificity at 78.9%.
  
  
  CONCLUSIONS
  NGAL may be a novel biomarker reflecting TBI severity, which increased obviously and negatively correlated with GCS, TS, and RTS scores; additionally, this characteristic of NGAL may be helpful in guiding clinical TBI therapeutic strategies.
authors.affiliation: Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, 264 Guangzhou Road, Nanjing 210029, Jiangsu Province, PR China. Electronic address: zjbbrain@163.com.
authors.forename: Jinbing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, The People's Hospital of Luhe, 9 Jiankang Lane, Nanjing 211500, Jiangsu Province, PR China.
authors.forename: Haodong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, Jiangsu Province, PR China.
authors.forename: Meijuan
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, 264 Guangzhou Road, Nanjing 210029, Jiangsu Province, PR China.
authors.forename: Yuhai
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, 264 Guangzhou Road, Nanjing 210029, Jiangsu Province, PR China.
authors.forename: Chunfa
authors.initials: C
authors.lastname: Qian
authors.affiliation: Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, 264 Guangzhou Road, Nanjing 210029, Jiangsu Province, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, 264 Guangzhou Road, Nanjing 210029, Jiangsu Province, PR China.
authors.forename: Shengxue
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, 264 Guangzhou Road, Nanjing 210029, Jiangsu Province, PR China.
authors.forename: Yuanjie
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, 264 Guangzhou Road, Nanjing 210029, Jiangsu Province, PR China.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001921:Brain / Q000378:metabolism; D000070642:Brain Injuries, Traumatic / Q000097:blood* / Q000473:pathology / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007958:Leukocyte Count; D000071068:Lipocalin-2 / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D013223:Statistics as Topic; D015599:Trauma Severity Indices
chemical_list: C489506:LCN2 protein, human; D000071068:Lipocalin-2
keywords: NGAL; Neurological severity; Traumatic brain injury