Early Blood Biomarkers Distinguish Inflammation from Neonatal Hypoxic-Ischemia Encephalopathy

Neonatal hypoxic-ischemic encephalopathy is the most common cause of neurological disability in infancy. Superimposed inflammation may further worsen neurological outcomes. Reliable biomarkers which are both sensitive to hypoxic-ischemia and inflammation are critically needed. We tested plasma osteopontin (OPN) and glial fibrillary astrocytic protein (GFAP) within the reported therapeutic window (90 min after hypoxic-ischemic (HI) injury) in neonatal rats with different HI severity and inflammation. Two different HI severity groups (mild-HI with 75 min hypoxia and severe-HI with 150 min hypoxia) were established. Inflammation-sensitized HI brain injury induced by lipopolysaccharide (LPS) further increased apoptotic neurons and infarct volumes. In HI alone groups, OPN was significantly decreased (p < 0.001) but GFAP was slightly increased (p < 0.05) at 90 min after HI either in mild-HI or severe-HI compared with naïve group. In LPS-sensitized HI groups, both OPN and GFAP were significantly increased either in LPS-mild-HI or LPS-severe-HI groups compared with the naïve group (all p < 0.05). Induced inflammation by LPS exaggerated neonatal HI brain injury. The plasma OPN and GFAP levels may be useful to differentiate HI alone groups from inflammation-sensitized HI groups or naïve group.