Experimental neurology
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Experimental neurology · Mar 2009
Task-dependent compensation after pyramidal tract and dorsolateral spinal lesions in rats.
The purpose of this research was to investigate whether pathways in the dorsal part of the lateral spinal funiculus (DLF) can compensate for loss of corticospinal input (CST) to the spinal cord. The CST is known to control skilled limb movements in rats. The DLF contains several different pathways, including the rubrospinal tract (RST) which is also thought to influence limb movements. ⋯ Our hypothesis was supported only for skilled pellet retrieval. Hence some DLF pathways, including the RST, were able to compensate for loss of CST input during skilled reaching but not during overground or skilled locomotion in PT-lesioned rats. These differential responses suggest that behavioural tasks vary in their reliance on specific pathways after injury, and, furthermore, that compensation for loss of specific connections can arise from numerous sources.
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Experimental neurology · Mar 2009
Pharmacological evidence for a role of peroxynitrite in the pathophysiology of spinal cord injury.
Evidence suggests that the reactive oxygen species peroxynitrite (PN) is an important player in the pathophysiology of acute spinal cord injury (SCI). In the present study, we examined the ability of tempol, a catalytic scavenger of PN-derived free radicals, to alleviate oxidative damage, mitochondrial dysfunction and cytoskeletal degradation following a severe contusion (200 kdyn force) SCI in female Sprague-Dawley rats. PN-mediated oxidative damage in spinal cord tissue, including protein nitration, protein oxidation and lipid peroxidation was significantly reduced by acute tempol treatment (300 mg/kg, i.p. within 5 min post-injury). ⋯ Increased levels of alpha-spectrin breakdown proteins (SBDP 145 kD and 150 kD) were significantly decreased at 24 h in tempol-treated rats indicative of spinal axonal protection. However, a therapeutic window analysis showed that the axonal cytoskeletal protective effects require tempol dosing within the first hour after injury. Nevertheless, these findings are the first to support the concept that PN is an important neuroprotective target in early secondary SCI, and that there is a mechanistic link between PN-mediated oxidative compromise of spinal cord mitochondrial function, loss of intracellular Ca(2+) homeostasis and calpain-mediated proteolytic axonal damage.