Wallerian degeneration

Introduction: Apoptosis, or secondary cell death, has been demonstrated in a number of neurological conditions, including Alzheimer's disease. Parkinson's disease, amyotrophic lateral sclerosis and brain ischaemia. It is well established from studies of acute spinal cord injury that apoplosis seems an important l;ictor in secondary cell death and irreversible neurological deficit. It is only recently that studies have emerged analysing secondary cell death in chronic injury to the cord. In this study, the spatial and temporal expression of apoptotic cells was analysed in acute traumatic spinal cord injury (SCl) (n=h) and chronic myelopathies due to metaslatic tumour (n=5). degenerative spondylosis (n=h) and syringomyelia (n=4).The study aimed to demonstrate apoptosis in compressive spinal cord injury and to analyse the spatial and temporal distribution of apoptosis in acute and chronic myelopathy.

Method: Archival material from 21 spinal cords ol patients with documented myelopathy during life and definitive evidence on post mortem examination were available fur study. The spatial and temporal expression ol apoptotic cells was analysed in acute traumatic spinal cord injury (SCI) (n=6) and chronic myelopathy due to metastatic tumour (n=5). degenerative spondylosis (n=A) and syringomyelia (n=4).

Immunohistochemical analysis of each specimen was conducted using markers of apoptosis, as well as the biochemical apoptotic marker TUNEL. A total of 1800 hislopathological slides were analysed. Specimens were also analysed using confocal microscopy to identify' the immunopositivc cell type. A combination of morphological, immunohistochemical and in situ end-labelling techniques were used to investigate the mechanism of eell death in this experiment.The analytical techniques employed were aimed at showing firstly the presence of apoptosis and sec ondly the size and position of the damaged regions.

Results: Positivily for active Caspase-3. DNA-PKCS, PARR TUNEL and active Caspase-9 was found in glia (oligodendrocytes and microglia) axons and neurons in both acute and chronic compression above, below and at the site of compression. In chronic compression, the severity of positivity for apoptotic immunological markers was positively correlated with the seventy of white matter damage, as measured by APP immunostaining for axonal injury, and Wallerian degeneration.ITiere was no correlation between the duration of chronic compression and immunopositivity for apoptotic markers. In acute SCI. axonal swellings were consistently positive for Caspases-9 and -3, suggesting milochondrial activation of apoptotic pathways.

Conclusion: Apoptosis occurs in both acute and chronic spinal cord injury. In acute compression, axonal injury is associated with apoptotic immunopositivity of glia and neurons. In chronic compression, apoptosis of oligodendrocytcs and microglia correlates with demyelination of axons within the white matter.

Newcombe. R.E.A.1,2, Blumbergs, P.C.2 Manavis. J2, Jones. N.R.1

1 Dept. Surgery, The University of Adelaide 5000

Australia and 2 Dept. Neuropathology, Institute of

Medical and Veterinary Science, Adelaide 5000

Australia.

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