Early expression of serum neutrophil gelatinase-associated lipocalin (NGAL) is associated with neurological severity immediately after traumatic brain injury

Abstract

Purpose: 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%.

Conclusion: 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.

Keywords: NGAL; Neurological severity; Traumatic brain injury.