Myelin basic protein and neurofilament H in postmortem cerebrospinal fluid as surrogate markers of fatal traumatic brain injury

Int J Legal Med. 2021 Jul;135(4):1525-1535. doi: 10.1007/s00414-021-02606-y. Epub 2021 Apr 24.

Abstract

The aim of this study was to investigate if the biomarkers myelin basic protein (MBP) and neurofilament-H (NF-H) yielded informative value in forensic diagnostics when examining cadaveric cerebrospinal fluid (CSF) biochemically via an enzyme-linked immunosorbent assay (ELISA) and comparing the corresponding brain tissue in fatal traumatic brain injury (TBI) autopsy cases by immunocytochemistry versus immunohistochemistry. In 21 trauma and 19 control cases, CSF was collected semi-sterile after suboccipital puncture and brain specimens after preparation. The CSF MBP (p = 0.006) and NF-H (p = 0.0002) levels after TBI were significantly higher than those in cardiovascular controls. Immunohistochemical staining against MBP and against NF-H was performed on cortical and subcortical samples from also biochemically investigated cases (5 TBI cases/5 controls). Compared to the controls, the TBI cases showed a visually reduced staining reaction against MBP or repeatedly ruptured neurofilaments against NF-H. Immunocytochemical tests showed MBP-positive phagocytizing macrophages in CSF with a survival time of > 24 h. In addition, numerous TMEM119-positive microglia could be detected with different degrees of staining intensity in the CSF of trauma cases. As a result, we were able to document that elevated levels of MBP and NF-H in the CSF should be considered as useful neuroinjury biomarkers of traumatic brain injury.

Keywords: Biofluid; Biomarker; CSF; Cerebrospinal fluid; Forensic neuropathology; Forensic neurotraumatology.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autopsy
  • Biomarkers / cerebrospinal fluid
  • Brain Injuries, Traumatic / diagnosis*
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunohistochemistry / methods
  • Male
  • Middle Aged
  • Myelin Basic Protein / cerebrospinal fluid*
  • Neurofilament Proteins / cerebrospinal fluid*

Substances

  • Biomarkers
  • Myelin Basic Protein
  • Neurofilament Proteins
  • neurofilament protein H