ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: The pathophysiology of traumatic spinal cord injury (SCI)involves abnormal activation of the neutral cysteine protease calpain I (EC3.4.22.17). In the present study we examined the effect of the calpaininhibitor CEP-4143 on cytoskeletal protection and neurological recovery afterSCI in adult rats. Microinjection of 50 mM CEP-4143 into the T7vertebral segment 10 min before a 35-g clip compression injury resulted ininhibition of calpain activation at 2 and 4 h postinjury, as determined bywestern blotting for calpain I-mediated spectrin degradation, andsignificantly attenuated the degradation of dephosphorylated NF200neurofilament protein at 4 and 8 h postinjury. To examine the in vivo chronicneuroprotective effects of CEP-4143, animals underwent microinjection withsaline or 50 mM CEP-4143 10 min before injury, followed by weeklyblinded behavioral assessments for 6 weeks. Animals receiving CEP-4143treatment showed significant improvement over saline-treated controls on theBasso Beattie Bresnahan locomotor rating scale (p 〈 0.02) andinclined plane test (p 〈 0.05). Counts of neurons in the red nucleus retrogradely labeled by fluorogold after introduction distal to the injury site were significantly higher in CEP-4143-treated animals. Finally, morphometric assessment of the injury site by computer-assisted image analysis revealed significant tissue preservation in CEP-4143-treated animals. We conclude that the calpain antagonist CEP-4143 exhibits biochemical, behavioral, and anatomical neuroprotection following traumatic SCI.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.2000.0741646.x
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