TUNEL-positive staining of surface contusions after fatal head injury in man

Fraser M. Smith, Ramesh Raghupathi, Mary Anne MacKinnon, Tracy K. McIntosh, Kathryn E. Saatman, David F. Meaney, D. I. Graham

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


In frontal lobe contusions obtained post mortem from 18 patients who survived between 6 h and 10 days after head injury, DNA fragmentation associated with either apoptotic and/or necrotic cell death was identified by the terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick end labelling (TUNEL) histochemical technique. Additional histological techniques were also used to identify regional and temporal patterns of tissue damage. TUNEL-positive cells were present in both the grey and white matter of the contusion, where they peaked in number between 25 and 48 h, and were still identifiable at 10 days post injury. Fewer TUNEL-positive cells were observed in grey than in white matter; and most TUNEL-positive neurons in the grey matter demonstrated the morphological features of necrosis. However, the morphology of some TUNEL-stained neurons, and of TUNEL-stained oligodendroglia and macrophages in white matter was suggestive of apoptosis. Apoptosis was not seen in age- and sex-matched controls, none of whom had died from intracranial pathology or had pre-existing neurological disease. These findings suggest that multiple cell types in frontal lobe contusions exhibit DNA fragmentation and that both necrosis and apoptosis are likely to contribute to post-traumatic pathology. These findings provide further evidence that the observations made in animal models of traumatic brain injury have fidelity with clinical head injury.

Original languageEnglish
Pages (from-to)537-545
Number of pages9
JournalActa Neuropathologica
Issue number5
StatePublished - 2000

Bibliographical note

Funding Information:
Acknowledgements Our thanks to Mrs. Marisa Hughes and Mrs. Gillian McFarlane for typing this manuscript and to Dr. L. Murray for statistical advice. This study was supported, in part, by a grant from the National Institutes of Neurological Disorders & Stroke (NINDS) of the National Institute of Health P50-NS08803, and ROI-NS26818, R01-GM34690 and a merit review grant from the Veterans Administration.


  • Human traumatic brain injury
  • TUNEL staining

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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