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Two different immunostaining patterns of beta-amyloid precursor protein (APP) may distinguish traumatic from nontraumatic axonal injury

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Abstract

Immunostaining for beta-amyloid precursor protein (APP) is recognized as an effective tool for detecting traumatic axonal injury, but it also detects axonal injury due to ischemic or other metabolic causes. Previously, we reported two different patterns of APP staining: labeled axons oriented along with white matter bundles (pattern 1) and labeled axons scattered irregularly (pattern 2) (Hayashi et al. (Leg Med (Tokyo) 11:S171-173, 2009). In this study, we investigated whether these two patterns are consistent with patterns of trauma and hypoxic brain damage, respectively. Sections of the corpus callosum from 44 cases of blunt head injury and equivalent control tissue were immunostained for APP. APP was detected in injured axons such as axonal bulbs and varicose axons in 24 of the 44 cases of head injuries that also survived for three or more hours after injury. In 21 of the 24 APP-positive cases, pattern 1 alone was observed in 14 cases, pattern 2 alone was not observed in any cases, and both patterns 1 and 2 were detected in 7 cases. APP-labeled injured axons were detected in 3 of the 44 control cases, all of which were pattern 2. These results suggest that pattern 1 indicates traumatic axonal injury, while pattern 2 results from hypoxic insult. These patterns may be useful to differentiate between traumatic and nontraumatic axonal injuries.

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References

  1. Selkoe DJ (1994) Normal and abnormal biology of the beta-amyloid precursor protein. Annu Rev Neurosci 17:489–517

    Article  CAS  PubMed  Google Scholar 

  2. Harrington D, Rutty GN, Timperley WR (2000) β-Amyloid precursor protein positive axonal bulbs may form in non-head-injured patients. J Clin Forensic Med 7:19–25

    Article  PubMed  Google Scholar 

  3. Sherriff FE, Bridges LR, Sivaloganathan S (1994) Early detection of axonal injury after human head trauma using immunocytochemistry for β-amyloid precursor protein. Acta Neuropathol 87:55–62

    Article  CAS  PubMed  Google Scholar 

  4. Sherriff FE, Bridges LR, Gentleman SM, Sivaloganathan S, Wilson S (1994) Markers of axonal injury in post mortem human brain. Acta Neuropathol 88:433–439

    Article  CAS  PubMed  Google Scholar 

  5. Gentleman SM, Roberts GW, Gennarelli TA, Maxwell WL, Adams JH, Kerr S, Graham DI (1995) Axonal injury: a universal consequence of fatal closed head injury? Acta Neuropathol 89:537–543

    Article  CAS  PubMed  Google Scholar 

  6. Blumbergs PC, Scott G, Manavis J, Wainwright H, Simpson DA, McLean AJ (1995) Topography of axonal injury as defined by amyloid precursor protein and the sector scoring method in mild and severe closed head injury. J Neurotrauma 12:565–572

    Article  CAS  PubMed  Google Scholar 

  7. McKenzie KJ, McLellan DR, Gentleman SM, Maxwell WL, Gennarelli TA, Graham DI (1996) Is beta-APP a marker of axonal damage in short-surviving head injury? Acta Neuropathol 92:608–613

    Article  CAS  PubMed  Google Scholar 

  8. Graham DI, Smith C, Reichard R, Leclercq PD, Gentleman SM (2004) Trials and tribulations of using beta-amyloid precursor protein immunohistochemistry to evaluate traumatic brain injury in adults. Forensic Sci Int 146:89–96

    Article  CAS  PubMed  Google Scholar 

  9. Ogata M (2007) Early diagnosis of diffuse brain damage resulting from a blunt head injury. Leg Med (Tokyo) 9:105–108

    Article  Google Scholar 

  10. Hortobágyi T, Wise S, Hunt N, Cary N, Djurovic V, Fegan-Earl A, Shorrock K, Rouse D, Al-Sarraj S (2007) Traumatic axonal damage in the brain can be detected using beta-APP immunohistochemistry within 35 min after head injury to human adults. Neuropathol Appl Neurobiol 33:226–237

    Article  PubMed  Google Scholar 

  11. Ogata M, Tsuganezawa O (1999) Neuron-specific enolase as an effective immunohistochemical marker for injured axons after fatal brain injury. Int J Legal Med 113:19–25

    Article  CAS  PubMed  Google Scholar 

  12. Oehmichen M, Meissner C, Schmidt V, Pedal I, König HG, Saternus KS (1998) Axonal injury—a diagnostic tool in forensic neuropathology? A review. Forensic Sci Int 95:67–83

    Article  CAS  PubMed  Google Scholar 

  13. Geddes JF, Whitwell HL, Graham DI (2000) Traumatic axonal injury: practical issues for diagnosis in medicolegal cases. Neuropathol Appl Neurobiol 26:105–116

    Article  CAS  PubMed  Google Scholar 

  14. Kaur B, Rutty GN, Timperley WR (1999) The possible role of hypoxia in the formation of axonal bulbs. J Clin Pathol 52:203–209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Oehmichen M, Meissner C, Schmidt V, Pedal I, König HG (1999) Pontine axonal injury after brain trauma and nontraumatic hypoxic-ischemic brain damage. Int J Legal Med 112:261–267

    Article  CAS  PubMed  Google Scholar 

  16. Hayashi T, Ago K, Ago M, Ogata M (2009) Two patterns of beta-amyloid precursor protein (APP) immunoreactivity in cases of blunt head injury. Leg Med (Tokyo) 11:S171–S173

    Article  Google Scholar 

  17. Davceva N, Janevska V, Ilievski B, Spasevska L, Popeska Z (2012) Dilemmas concerning the diffuse axonal injury as a clinicopathological entity in forensic medical practice. J Forensic Leg Med 19:413–418

    Article  CAS  PubMed  Google Scholar 

  18. Oehmichen M, Meissner C, von Wurmb-Schwark N, Schwark T (2003) Methodical approach to brain hypoxia/ischemia as a fundamental problem in forensic neuropathology. Leg Med (Tokyo) 5:190–201

    Article  CAS  Google Scholar 

  19. Neil J, Miller J, Mukherjee P, Hüppi PS (2002) Diffusion tensor imaging of normal and injured developing human brain—a technical review. NMR Biomed 15:543–552

    Article  CAS  PubMed  Google Scholar 

  20. Sundgren PC, Dong Q, Gómez-Hassan D, Mukherji SK, Maly P, Welsh R (2004) Diffusion tensor imaging of the brain: review of clinical applications. Neuroradiology 46:339–350

    Article  CAS  PubMed  Google Scholar 

  21. Huisman TA, Schwamm LH, Schaefer PW, Koroshetz WJ, Shetty-Alva N, Ozsunar Y, Wu O, Sorensen AG (2004) Diffusion tensor imaging as potential biomarker of white matter injury in diffuse axonal injury. AJNR Am J Neuroradiol 25:370–376

    PubMed  Google Scholar 

  22. Mori S, Zhang J (2006) Principles of diffusion tensor imaging and its applications to basic neuroscience research. Neuron 51:527–539

    Article  CAS  PubMed  Google Scholar 

  23. Arfanakis K, Haughton VM, Carew JD, Rogers BP, Dempsey RJ, Meyerand ME (2002) Diffusion tensor MR imaging in diffuse axonal injury. AJNR Am J Neuroradiol 23:794–802

    PubMed  Google Scholar 

  24. Field AS, Hasan K, Jellison BJ, Arfanakis K, Alexander AL (2003) Diffusion tensor imaging in an infant with traumatic brain swelling. AJNR Am J Neuroradiol 24:1461–1464

    PubMed  Google Scholar 

  25. Li S, Sun Y, Shan D, Feng B, Xing J, Duan Y, Dai J, Lei H, Zhou Y (2013) Temporal profiles of axonal injury following impact acceleration traumatic brain injury in rats—a comparative study with diffusion tensor imaging and morphological analysis. Int J Legal Med 127:159–167

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was financially supported by Grants-in-Aids for Scientific Research (C) (grant no. 19590677 to M. Ogata) and for Young Scientists (B) (grant no. 22790599 to T. Hayashi) from the Ministry of Education, Culture, Science, and Technology of Japan.

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The authors have no conflict of interest to declare.

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Correspondence to Takahito Hayashi.

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Hayashi, T., Ago, K., Nakamae, T. et al. Two different immunostaining patterns of beta-amyloid precursor protein (APP) may distinguish traumatic from nontraumatic axonal injury. Int J Legal Med 129, 1085–1090 (2015). https://doi.org/10.1007/s00414-015-1245-8

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  • DOI: https://doi.org/10.1007/s00414-015-1245-8

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