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Post-mortem cerebrospinal fluid diagnostics: cytology and immunocytochemistry method suitable for routine use to interpret pathological processes in the central nervous system


Due to its protected anatomical location, cerebrospinal fluid (CSF) is a very stable fluid which undergoes comparatively little change in the early post-mortem phase. While many immunohistochemical markers already established for clinical diagnostic issues in tissue samples obtained by biopsy could meanwhile be translated also to post-mortem tissue, no systematic immunocytochemical investigations have generally been conducted on post-mortem body fluids and for CSF specifically, have not been established at all. CSF as the fluid directly surrounding the brain should also be examined to allow a more detailed characterization of processes in the central nervous system. Comparing traumatized tissue and CSF can complete forensic assessment and complement neuropathological evaluation.

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  1. Friedrich G (1986) Forensische postmortale Biochemie. In: Forster B (ed) Praxis der Rechtsmedizin. Thieme, Stuttgart, pp 789–831

    Google Scholar 

  2. Kernbach G, Brinkmann B (1983) Postmortale Pathochemie für die Feststellung der Todesursache "Coma diabeticum". Pathologe 4:235–240

    CAS  PubMed  Google Scholar 

  3. Palmiere C, Mangin P (2012) Postmortem chemistry update part II. Int J Legal Med 126:199–215

    Article  Google Scholar 

  4. Trautz F, Dressler J, Stassart R, Muller W, Ondruschka B (2018) Proposals for best-quality immunohistochemical staining of paraffin-embedded brain tissue slides in forensics. Int J Legal Med 132(4):1103–1109

    Article  Google Scholar 

  5. Wyler D, Marty W, Bär W (1994) Correlation between the post-mortem cell content of cerebrospinal fluid and time of death. Int J Legal Med 106:194–199

    CAS  Article  Google Scholar 

  6. Swain R, Kumar A, Sahoo J, Lakshmy R, Gupta S, Bhardwaj D, Pandey R (2015) Estimation of post-mortem interval: a comparison between cerebrospinal fluid and vitreous humour chemistry. J Forensic Legal Med 36:144–148

    Article  Google Scholar 

  7. Mangin P, Lugnier A-A, Chaumont A-J, Offner M, Grucker M (1993) Forensic significance of postmortem estimation of the blood cerebrospinal fluid barrier permeability. Forensic Sci Int 22:143–149

    Article  Google Scholar 

  8. Hausmann R, Betz P (2000) The time course of the vascular response to human brain injury- an immunohistochemical study. Int J Legal Med 113:288–292

    CAS  Article  Google Scholar 

  9. Hausmann R, Betz P (2001) Course of glial immunoreactivity for vimentin, tenascin and alpha 1-antichymotrypsin after traumatic injury to human brain. Int J Legal Med 114:338–342

    CAS  Article  Google Scholar 

  10. Oehmichen M, Walter T, Meissner C, Friedrich H (2003) Time course of cortical hemorrhages after closed traumatic brain injury: statistical analysis of posttraumatic histomorphological alterations. J Neurotrauma 20:87–103

    Article  Google Scholar 

  11. Dreßler J, Hanisch U, Kuhlisch E, Geiger K (2007) Neuronal and glial apoptosis in human traumatic brain injury. Int J Legal Med 121:365–375

    Article  Google Scholar 

  12. Krohn M, Dreßler J, Bauer M, Schober K, Franke H, Ondruschka B (2015) Immunohistochemical investigation of S100 and NSE in cases of traumatic brain injury and its application for survival time determination. J Neurotrauma 32:430–440

    Article  Google Scholar 

  13. Ondruschka B, Schuch S, Pohlers D, Franke H, Dreßler J (2018) Acute phase response after fatal traumatic brain injury. Int J Legal Med 132:531–539

    Article  Google Scholar 

  14. Bayer R, Franke H, Ficker C, Richter M, Lessig R, Büttner A, Weber M (2015) Alterations of neuronal precursor cells in stages of human adult neurogenesis in heroin addicts. Drug Alcohol Depend 156:139–149

    Article  Google Scholar 

  15. Büttner A (2011) The neuropathology of drug abuse. Neuropathol Appl Neurobiol 37:118–134

    Article  Google Scholar 

  16. Weber M, Scherf N, Kahl T, Braumann U, Scheibe P, Kuska J, Bayer R, Büttner A, Franke H (2013) Quantitative analysis of astrogliosis in drug-dependent humans. Brain Res 1500:72–87

    CAS  Article  Google Scholar 

  17. Weis S, Büttner A (2017) Neurotoxicology and drug-related disorders. Handb Clin Neurol 145:181–192

  18. Jones K, Krous H, Nadeau J, Blackbourne B, Zielke H, Gozal D (2003) Vascular endothelial growth factor in cerebrospinal fluid of infants who died of sudden infant death syndrome: evidence for antecedent hypoxia. Pediatrics 111:358–363

    Article  Google Scholar 

  19. Quan L, Ishikawa T, Hara J, Michiue T, Chen J-H, Wang Q, Zhu B, Maeda H (2011) Postmortem serotonin levels in cerebrospinal and pericardial fluids with regard to the cause of death in medicolegal autopsy. Leg Med (Tokyo) 13:75–78

    CAS  Article  Google Scholar 

  20. Rognum I, Tran H, Haas E, Hyland K, Paterson D, Haynes R, Broadbelt K, Harty B, Mena O, Krous H, Kinney H (2014) Serotonin metabolites in the cerebrospinal fluid in sudden infant death syndrome. J Neuropathol Exp Neurol 73:115–122

    CAS  Article  Google Scholar 

  21. Agoston DV, Shutes-David A, Peskind E (2017) Biofluid biomarkers of traumatic brain injury. Brain Inj 31:1195–1203

    Article  Google Scholar 

  22. Olczak M, Niderla-Bielinska J, Kwiatkowska M, Samojlowicz D, Tarka S, Wierzba-Bobrowicz T (2017) Tau protein (MAPT) as a possible biochemical marker of traumatic brain injury in pstmortem examination. Forensic Sci Int 280:1–7

    CAS  Article  Google Scholar 

  23. Ondruschka B, Sieber M, Kirsten H, Franke H, Dreßler J (2018) Measurement of cerebral biomarkers proving traumatic brain injury in post-mortem body fluids. Neurotrauma 17:2044–2055

    Article  Google Scholar 

  24. Sieber M, Dreßler J, Franke H, Pohlers D, Oehmichen M (2018) Post-mortem biochemistry of NSE and S100B: a supplemental tool for detecting a lethal traumatic brain injury. J Forensic Legal Med 55:65–73

    Article  Google Scholar 

  25. Oerter S, Förster C, Bohnert M (2018) Validation of sodium/glucose cotransporter proteins in human brain as a potential marker for temporal narrowing of the trauma formation. Int J Legal Med.

  26. Ondruschka B, Pohlers D, Somemr G, Schober J, Teupser D, Franke H, Dreßler J (2013) S100B and NSE as useful postmortem biochemical markers of traumatic brain injury in autopsy cases. J Neurotrauma 30:1862–1871

    Article  Google Scholar 

  27. Deutsche Gesellschaft für Rechtsmedizin (2017) Die rechtsmedizinische Leichenöffnung. AWMF.

  28. Dettmeyer R (2018) Forensic histopathology. 2nd. Springer, Berlin

    Book  Google Scholar 

  29. Hanrieder J, Wetterhall M, Enblad P, Hillered L, Bergquist J (2009) Temporally resolved differential proteomic analysis of human ventricular CSF monitoring traumatic brain injury biomarker candidates. J Neurosci Methods 177:469–478

    CAS  Article  Google Scholar 

  30. Hausmann R, Betz P (2002) The course of MIB-1 expression by cerebral macrophages following human brain injury. Leg Med (Tokyo) 4:79–83

    CAS  Article  Google Scholar 

  31. Garland J, Philox W, Kesha K, Morrow P, Lam L, Spark A, Palmiere C, Elstub H, Cala A, Stables S, Tse R (2018) Differences in sampling site on the postmortem cerebrospinal fluid biochemistry: a preliminary study. Am J Forensic Med Pathol 39:304–308

    PubMed  Google Scholar 

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We would like to thank the preparators Heiko Besenfelder and Max Perschneck for their excellent support in collecting the specimens and Michaela Hartmann as well as the team of the CSF laboratory of the Neurological University Hospital for producing the preparations and stains.

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Correspondence to Simone Bohnert.

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This study has been reviewed and approved by the ethic committee of the University of Wuerzburg.

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Bohnert, S., Ondruschka, B., Bohnert, M. et al. Post-mortem cerebrospinal fluid diagnostics: cytology and immunocytochemistry method suitable for routine use to interpret pathological processes in the central nervous system. Int J Legal Med 133, 1141–1146 (2019).

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  • CSF
  • Cerebrospinal fluid
  • Forensic neuropathology
  • Forensic neurotraumatology
  • Cytology
  • Immunocytochemistry