Neurotrauma Reports (Aug 2021)

Blood-Based Brain and Global Biomarker Changes after Combined Hypoxemia and Hemorrhagic Shock in a Rat Model of Penetrating Ballistic-Like Brain Injury

  • Xue Li,
  • Kevin Pierre,
  • Zhihui Yang,
  • Lynn Nguyen,
  • Gabrielle Johnson,
  • Juliana Venetucci,
  • Isabel Torres,
  • Brandon Lucke-Wold,
  • Yuan Shi,
  • Angela Boutte,
  • Deborah Shear,
  • Lai Yee Leung,
  • Kevin K.W. Wang

DOI
https://doi.org/10.1089/NEUR.2021.0006
Journal volume & issue
Vol. 2, no. 1
pp. 370 – 380

Abstract

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Penetrating traumatic brain injury (pTBI) often occurs with systemic insults such as hemorrhagic shock (HS) and hypoxemic (HX). This study examines rat models of penetrating ballistic-like brain injury (PBBI) and HX+HS to assess whether the blood levels of brain and systemic response biomarkers phosphorylated neurofilament-heavy protein (pNF-H), neurofilament-light protein (NF-L), ?II-spectrin, heat shock protein (HSP70), and high mobility group box 1 protein (HMGB1) can distinguish pTBI from systemic insults and guide in pTBI diagnosis, prognosis, and monitoring. Thirty rats were randomly assigned to sham, PBBI, HS+HX, and PBBI+HS+HX groups. PBBI and sham groups underwent craniotomy with and without probe insertion and balloon expansion, respectively. HX and HS was then simulated by blood withdrawal and fraction of inspired oxygen (FIO2) reduction. Biomarker serum concentrations were determined at one (D1) and two (D2) days post-injury with enzyme-linked immunosorbent assay (ELISA) methods. Axonal injury-linked biomarkers pNF-H and NF-L serum levels in PBBI groups were higher than those in sham and HX+HS groups at D1 and D2 post-injury. The same was true for PBBI+HX+HS compared with sham (D2 only for pNF-H) and HX+HS groups. However, pNF-H and NF-L levels in PBBI+HX+HS groups were not different than their PBBI counterparts. At D1, ?II-spectrin levels in the HX+HS and PBBI+HS+HX groups were higher than the sham groups. ?II-spectrin levels in the HX+HS group were higher than the PBBI group. This suggests HX+HS as the common insult driving ?II-spectrin elevations. In conclusion, pNF-H and NF-L may serve as specific serum biomarkers of pTBI in the presence or absence of systemic insults. ?II-spectrin may be a sensitive acute biomarker in detecting systemic insults occurring alone or with pTBI.

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