• P A Schumacher, J H Eubanks, and M G Fehlings.
• Playfair Neuroscience Unit and The Toronto Hospital Research Institute, University of Toronto, The Toronto Hospital, Ontario, Canada.
• Neuroscience. 1999 Jan 1;91(2):733-44.

AbstractWe investigated the hypothesis that the Ca2+-activated protease calpain is involved in the pathophysiology of spinal cord injury, and is linked to the proteolytic degradation of cytoskeletal proteins. We report here that levels of calpain I (mu-calpain)-mediated spectrin breakdown products are increased by 15 min post-injury, with peak levels reached by 2 h post-injury. The dephosphorylated form of the neurofilament protein NF200 is substantially lost over the same time-period. A 35-g compressive injury was applied to the midthoracic rat spinal cord for 1 min, and animals were killed at 15 min, 1, 2, 4, 8, 16, and 24 h post-injury. Calpain I-mediated spectrin breakdown products accumulated post-injury, with peak levels reached at 2 h. Secondly, we have demonstrated a progressive loss of the 200,000 mol. wt neurofilament protein NF200, a cytoskeletal calpain substrate, which began within 1-2 h post-injury. Densitometric analyses confirmed that loss of NF200 is a substrate-specific phenomenon, since (i) dephosphorylated NF200 was preferentially lost while phosphorylated NF200 was relatively spared, and (ii) actin, which is not a substrate for calpain, was relatively spared following spinal cord injury. Finally, we demonstrated calpain I-mediated spectrin breakdown within NF200-positive neuronal processes post-injury. We conclude that the accumulation of spectrin breakdown products is temporally and spatially correlated with loss of dephosphorylated NF200 after spinal cord injury.

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