Graft repair of the peroneal nerve restores histochemical profile after long-term reinnervation of the rat extensor digitorum longus muscle in contrast to end-to-end repair

Declining motor function is a prominent feature of ageing physiology. One reason for this is a reduction in plasticity that normally compensates for ongoing reorganization of motor units under physiological conditions. Previous work from our laboratory has shown that microsurgical repair of the transected peroneal nerve is followed by considerable changes in the histochemical profile of the reinnervated extensor digitorum longus (EDL) muscle and that these changes are dependent on both the time and the type of nerve repair. At 6 months postoperatively, a trend toward reversibility could be discerned. In the present work, we analysed the long-term reorganization of histochemical motor unit distribution patterns 15 months after performing either end-to-end repair or grafting of the peroneal nerve in 3-month-old rats. In addition, the EDL muscles of an age-matched control group (age 18 months) were analysed for age-dependent changes. We observed a loss of histochemical organization of motor units leading to an additional fibre type (SDH-INT) in the control group. Fifteen months after end-to-end repair, the histochemical profile showed a decrease in fibre type IIA and an increase in fibre type SDH-INT (P < 0.05), indicating a profound histochemical disorganization of motor units. In contrast, nerve grafting largely restored the histochemical profile of reinnervated EDL muscles. Fibre type grouping was present after both types of nerve repair. These findings show that reorganization of the histochemical profile in reinnervated muscles is dependent on the time and type of nerve repair and is long lasting. In this study, grafting provided superior results compared with end-to-end repair. These long-term results after peripheral nerve repair are influenced by age-dependent changes. Accordingly, nerve repair reduces the normal functional plasticity of motor unit organization. This reduction is enhanced by increasing age

Neuroprotective Effects of N-Acetyl-Cysteine and Acetyl-L-Carnitine after Spinal Cord Injury in Adult Rats

Following the initial acute stage of spinal cord injury, a cascade of cellular and inflammatory responses will lead to progressive secondary damage of the nerve tissue surrounding the primary injury site. The degeneration is manifested by loss of neurons and glial cells, demyelination and cyst formation. Injury to the mammalian spinal cord results in nearly complete failure of the severed axons to regenerate. We have previously demonstrated that the antioxidants N-acetyl-cysteine (NAC) and acetyl-L-carnitine (ALC) can attenuate retrograde neuronal degeneration after peripheral nerve and ventral root injury. The present study evaluates the effects of NAC and ALC on neuronal survival, axonal sprouting and glial cell reactions after spinal cord injury in adult rats. Tibial motoneurons in the spinal cord were pre-labeled with fluorescent tracer Fast Blue one week before lumbar L5 hemisection. Continuous intrathecal infusion of NAC (2.4 mg/day) or ALC (0.9 mg/day) was initiated immediately after spinal injury using Alzet 2002 osmotic minipumps. Neuroprotective effects of treatment were assessed by counting surviving motoneurons and by using quantitative immunohistochemistry and Western blotting for neuronal and glial cell markers 4 weeks after hemisection. Spinal cord injury induced significant loss of tibial motoneurons in L4-L6 segments. Neuronal degeneration was associated with decreased immunostaining for microtubular-associated protein-2 (MAP2) in dendritic branches, synaptophysin in presynaptic boutons and neurofilaments in nerve fibers. Immunostaining for the astroglial marker GFAP and microglial marker OX42 was increased. Treatment with NAC and ALC rescued approximately half of the motoneurons destined to die. In addition, antioxidants restored MAP2 and synaptophysin immunoreactivity. However, the perineuronal synaptophysin labeling was not recovered. Although both treatments promoted axonal sprouting, there was no effect on reactive astrocytes. In contrast, the microglial reaction was significantly attenuated. The results indicate a therapeutic potential for NAC and ALC in the early treatment of traumatic spinal cord injury