Evaluation of Specific Neural Marker GAP-43 and TH Combined With Masson-trichrome Staining for Forensic Autopsy Cases With Old Myocardial Infarction

Int J Legal Med. 2018 Jan;132(1):187-195. doi: 10.1007/s00414-017-1590-x. Epub 2017 Apr 11.


It has been a puzzling forensic task to determine the cause of death as a result of old myocardial infarction (OMI) in the absence of recognizable acute myocardial infarction. Recent studies indicated that the heterogeneous cardiac nerve sprouting and sympathetic hyperinnervation at border zones of the infarcted site played important roles in sudden cardiac death (SCD). So, the present study explored the value of growth associated protein-43 (GAP-43) and tyrosine hydroxylase (TH) as objective and specific neural biomarkers combined with Masson-trichrome staining for forensic autopsy cases. Myocardium of left ventricle of 58 medicolegal autopsy cases, 12 OMI cases, 12 acute/OMI cases, and 34 control cases, were immunostained with anti-GAP-43 and anti-TH antibodies. Immunoreactivity of GAP-43 and TH identified nerve fibers and vascular wall in OMI cases and acute/OMI cases. Specifically, TH-positive nerve fibers were abundant at border zones of the infarcted site. There were a few GAP-43 and TH expressions in the control cases. With Masson-trichrome staining, collagen fibers were blue and cardiac muscle fibers were pink in marked contrast with the surrounding tissue, which improved the location of nerve fibers. Thus, these findings suggest that immunohistochemical detection of GAP-43 and TH combined with Masson-trichrome staining can provide the evidence for the medicolegal expertise of SCD due to OMI, and further demonstrate a close relationship between sympathetic hyperinnervation and SCD.

Keywords: Forensic pathology; Growth associated protein-43 (GAP-43); Nerve sprouting; Sympathetic hyperinnervation; Tyrosine hydroxylase (TH).

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / metabolism
  • Case-Control Studies
  • Death, Sudden, Cardiac / pathology
  • Female
  • GAP-43 Protein / metabolism*
  • Heart / innervation
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Myocardial Infarction / metabolism*
  • Myocardial Infarction / pathology
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Nerve Fibers / metabolism
  • Staining and Labeling / methods*
  • Sympathetic Nervous System / physiopathology
  • Tyrosine 3-Monooxygenase / metabolism*
  • Young Adult


  • Biomarkers
  • GAP-43 Protein
  • Tyrosine 3-Monooxygenase