To determine the association between plasma lipocalin-2/NGAL and functional outcome in subarachnoid hemorrhage (SAH) patients.

Studies show that neuroinflammation plays a crucial role in SAH-associated brain injury. Lipocalin-2/NGAL mediates neuroinflammation in SAH animal models. Here, we suppose that Lipocalin-2/NGAL is associated with functional outcome in SAH patients.

We included 67 subjects from a SAH cohort with banked serial blood samples and prospective evaluation of modified Rankin Scale (mRS) score at 3-month intervals. Poor functional outcome was defined as mRS > 2. Angiographic vasospasm was defined as > 50% reduction in the caliber of any vessel in later cerebral angiogram. Any patients who presented beyond 96 hours of SAH onset, had secondary SAH or other intracranial outstanding conditions (malignancy, meningitis, etc) and chronic kidney/hepatic disease were excluded. Lipocalin-2/NGAL was measured using Human Magnetic Luminex Assay (R&D Systems) at day 1, 3 and 5 post SAH. Patients with unruptured cerebral aneurysm were included as control group (N=19). Continuous variables were compared with Student’s t or Wilcoxon rank sum test depending on data distribution. One-way ANOVA was applied for comparison among more than 2 groups.

The overall cohort had mean age of 55.1 years and had 69% women. Majority of the cohort had Hunt and Hess grade 3 or above (67%) and modified Fisher grade 3-4 (89%). Overall, 48% and 36% patients developed poor outcome at 3- and 6-month post SAH, and 55% developed vasospasm. Within the SAH cohort, higher lipocalin-2/NGAL and Ln lipocalin-2/NGAL were associated with poor 3-month outcome (p=0.0044) and poor 6-month outcome (p=0.0417), respectively.

Early elevation of plasma Lipocalin-2/NGAL is associated with poor neurofunctional recovery in SAH patients. Detailed mechanisms are needed to understand the role of Lipocalin-2/NGAL in SAH and develop potential Lipocalin-2/NGAL-based therapy.