Brain Advance Access originally published online on October 8, 2003
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Brain, Vol. 127, No. 1, 34-44, 2004
© 2004 Guarantors of Brain
doi: 10.1093/brain/awh001
Gradual loss of myelin and formation of an astrocytic scar during Wallerian degeneration in the human spinal cord
1 Department of Neurology, Aachen University Medical School, Pauwelsstrasse 30, Germany, 2 Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Australia, and 3 Department of Neurosurgery, Sart Tilman Hospital, 4 Department of Neurology and Neuropathology and 5 Center for Cellular and Molecular Neuroscience, University of Liège, Liège, Belgium
Correspondence to: Armin Buss, Department of Neurology, Aachen University Hospital, Pauwelsstrasse 30, 52074 Aachen, Germany E-mail: arminbuss{at}hotmail.com
Axons undergo Wallerian degeneration distal to a point of injury. Experimental investigations have documented many of the cellular and molecular events that underlie this behaviour. Since relatively little is known about such events in human CNS pathologies and current experimental intervention strategies indicate the possibility of significant axon regeneration along the original degenerated fibre tract, we performed an immunohistochemical investigation of the dynamics of Wallerian degeneration in post mortem spinal cords of patients who died 2 days to 30 years after either cerebral infarction or traumatic spinal cord injury. Neurofilament (NF) staining demonstrated a spatio-temporal pattern of axonal loss within degenerating descending nerve fibre tracts that could be detected close to the lesion as early as 12 days after injury and progressed to an almost complete loss of NF immunoreactivity at survival times of 1 year and longer. Immunohistochemistry for glial fibrillary acidic protein revealed a late astrocytic reaction starting at 4 months after injury in the degenerating tracts, leading to the long-term deposition of a dense astrocytic scar. These events were accompanied by the gradual reduction of myelin basic protein in affected nerve fibre tracts, leading to almost complete loss by 3 years after injury. Since the extracellular matrix molecule chondroitin sulphate proteoglycan (CSPG) is known to be strongly inhibitory for axonal regeneration and to be a major component of gliotic scar tissues, we investigated the possible deposition of CSPG within the degenerating nerve fibre tracts. Apart from a local up-regulation close to the lesion site, our results show no enhanced CSPG expression within degenerated tracts at any survival time. This suggests that despite the apparent lack of CSPG in Wallerian degeneration, the slow reduction of CNS myelin and the long-term deposition of a dense astrocytic scar may present an environment that is non-supportive for axon regrowth.
Key Words: astrocyte; CSPG; GFAP; myelin; Wallerian degeneration
Abbreviations: CSPG = chondroitin sulphate proteoglycan; CST = corticospinal tract; GFAP = glial fibrillary acidic protein; MBP = myelin basic protein; NF = neurofilament
Received March 18, 2003. Revised July 8, 2003. Accepted July 17, 2003.
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