Search

We present an updated, clinically relevant model of moderately severe bilateral cervical level 6 contusive spinal cord injury (SCI) in the rat. This model is more clinically relevant than previous models due it its severity, yet animals readily survive the lesion. The C6 bilateral lesion is administered to Fischer 344 rats using the Infinite Horizons impactor adjusted to a 200 kdyne force with a 3.5 mm impactor head. The lesion results in loss of 60 ± 10% of the spinal cord area, including virtually the entire dorsal half of the spinal cord and complete interruption of the main corticospinal tract. Skilled forelimb performance declines by 60 ± 10% compared to the pre-operative baseline and deficits are sustained over time. This model is a substantial step closer to mimicking the most common level (cervical) and more severe form of SCI in humans and should provide a superior tool for assessing the likelihood that experimental interventions may promote motor recovery after SCI in humans. • In the present study we highlight the following discoveries: • A clinically relevant model of moderately severe bilateral C6 contusive spinal cord injury is adapted in Fischer 344 rats. • About 60% of the spinal cord area is lost in the injury epicenter, including the main tract of corticospinal axons. • About 60% of skilled forelimb reaching and grasping performance declines after injury. [ABSTRACT FROM AUTHOR]

G-CSF is a glycoprotein commonly used to treat neutropenia. Recent studies have shown that the G-CSF receptor (G-CSF-R) is expressed by neurons in the central nervous system (CNS), and neuroprotective effects of G-CSF have been observed. In this study, the influence of G-CSF treatment on the glial reactivity and synaptic plasticity of spinal motoneurons in rats subjected to ventral root avulsion (VRA) was investigated. Lewis rats (7 weeks old) were subjected to unilateral VRA and divided into two groups: G-CSF and placebo treated. The drug treated animals were injected subcutaneously with 200 μg/kg/day of G-CSF for 5 days post lesion. The placebo group received saline buffer. After 2 weeks, both groups were sacrificed and their lumbar intumescences processed for transmission electron microscopy (TEM), motoneuron counting, and immunohistochemistry with antibodies against GFAP, Iba-1, and synaptophysin. Furthermore, in vitro analysis was carried out, using newborn cortical derived astrocytes. The results indicated increased neuronal survival in the G-CSF treated group coupled with synaptic preservation. TEM analyses revealed an improved preservation of the synaptic covering in treated animals. Additionally, the drug treated group showed an increase in astroglial reactivity both in vivo and in vitro. The astrocytes also presented an increased cell proliferation rate when compared with the controls after 3 days of culturing. In conclusion, the present results suggest that G-CSF has an influence on the stability of presynaptic terminals in the spinal cord as well as on the astroglial reaction, indicating a possible neuroprotective action. Synapse, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) leads to irreversible functional impairment caused by neuronal loss and the disruption of neuronal connections across the injury site. While several experimental strategies have been used to minimize tissue damage and to enhance axonal growth and regeneration, the corticospinal projection, which is the most important voluntary motor system in humans, remains largely refractory to regenerative therapeutic interventions. To date, one of the most promising pre-clinical therapeutic strategies has been neural stem cell (NSC) therapy for SCI. Over the last decade we have found that host axons regenerate into spinal NSC grafts placed into sites of SCI. These regenerating axons form synapses with the graft, and the graft in turn extends very large numbers of new axons from the injury site over long distances into the distal spinal cord. Here we discuss the pathophysiology of SCI that makes the spinal cord refractory to spontaneous regeneration, the most recent findings of neural stem cell therapy for SCI, how it has impacted motor systems including the corticospinal tract and the implications for sensory feedback. [ABSTRACT FROM AUTHOR]

Abstract: Avulsion of ventral roots induces degeneration of most axotomized motoneurons. At present there are no effective strategies to prevent such neuronal loss and to preserve the affected spinal circuits. Interestingly, changes in the spinal cord network also occur during the course of the experimental model of multiple sclerosis (experimental autoimmune encephalomyelitis—EAE). Glatiramer acetate (GA) significantly reduces the seriousness of the symptoms during the exacerbation of EAE. However, little is known about its effects on motoneurons. In the present study, we investigated whether GA has an influence on synapse plasticity and glial reaction after ventral root avulsion (VRA). Lewis rats were subjected to the avulsion of lumbar ventral roots and treated with GA. The animals were sacrificed after 14 days of treatment and the spinal cords processed for immunohistochemistry. A correlation between the synaptic changes and glial activation was obtained by performing immunolabeling against synaptophysin, GFAP and Iba-1. GA treatment preserved synaptophysin labeling, and significantly reduced the glial reaction in the area surrounding the axotomized motoneurons. After ventral root avulsion, GA treatment was also neuroprotective. The present results indicate that the immunomodulator GA has an influence on the stability of nerve terminals in the spinal cord, which may in turn contribute to future treatment strategies after proximal lesions to spinal motoneurons. [Copyright &y& Elsevier]

Denervation induces muscle fiber atrophy and changes in the gene expression rates of skeletal muscle. Electrical stimulation (ES) is a procedure generally used to treat denervated muscles in humans. This study evaluated the effect of ES based on chronaxie and rheobase on the expression of the myoD and atrogin-1 genes in denervated tibialis anterior (TA) muscle of Wistar rats. Five groups were examined: (1) denervated (D); (2) D+ES; (3) sham denervation; (4) normal (N); and (5) N+ES. Twenty muscle contractions were stimulated every 48 h using surface electrodes. After 28 days, ES significantly decreased the expression of myoD and atrogin-1 in D+ES compared to the D group. However, ES did not prevent muscle-fiber atrophy after denervation. Thus, ES based on chronaxie values and applied to denervated muscles using surface electrodes, as normally used in human rehabilitation, was able to reduce the myoD and atrogin-1 gene expressions, which are related to muscular growth and atrophy, respectively. The results of this study provide new information for the treatment of denervated skeletal muscle using surface ES. [ABSTRACT FROM AUTHOR]