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Early Blood Biomarkers Distinguish Inflammation from Neonatal Hypoxic-Ischemia Encephalopathy

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Abstract

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.

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Acknowledgements

We would like to thank Dr. Chi-Wu Chiang for critical comments and discussion on the manuscript, Dr. Wen-Hao Yu for supervising surgical procedures, the staff in the laboratory of National Cheng Kung University and two summer students (Ming-Chien Tu, Ming-June Tu) for their efforts in laboratory works.

Funding

This study was supported by grants from National Cheng Kung University Hospital (NCKUH- 10506011, 10705019) and Ministry of Science and Technology (MOST-106-2314-B006-065, 106-2314-B-006-075, 107-2314-B-006-005, 108-2314-B-006 -027-MY2, 108-2314-B-006-002) of Taiwan.

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Authors and Affiliations

  1. Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Po-Ming Wu, Chao-Ching Huang & Yi-Fang Tu

  2. Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Po-Ming Wu & Yi-Fang Tu

  3. Department of Emergency Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Chih-Hao Lin & Hsin-I Shih

  4. Institute of Anatomy & Cell Biology, National Yang-Ming University, Taipei, Taiwan

    Hsueh-Te Lee

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Wu, PM., Lin, CH., Lee, HT. et al. Early Blood Biomarkers Distinguish Inflammation from Neonatal Hypoxic-Ischemia Encephalopathy. Neurochem Res 45, 2712–2722 (2020). https://doi.org/10.1007/s11064-020-03119-7

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