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  • Title: Dynamics of early locomotor network dysfunction following a focal lesion in an in vitro model of spinal injury.
    Author: Taccola G, Mladinic M, Nistri A.
    Journal: Eur J Neurosci; 2010 Jan; 31(1):60-78. PubMed ID: 20092556.
    Abstract:
    It is unclear how a localized spinal cord injury may acutely affect locomotor networks of segments initially spared by the lesion. To investigate the process of secondary damage following spinal injury, we used the in vitro model of the neonatal rat isolated spinal cord with transverse barriers at the low thoracic-upper lumbar region to allow focal application of kainate in hypoxic and aglycemic solution (with reactive oxygen species). The time-course and nature of changes in spinal locomotor networks downstream of the lesion site were investigated over the first 24 h, with electrophysiological recordings monitoring fictive locomotion (alternating oscillations between flexor and extensor motor pools on either side) and correlating any deficit with histological alterations. The toxic solution irreversibly suppressed synaptic transmission within barriers without blocking spinal reflexes outside. This effect was focally associated with extensive white matter damage and ventral gray neuronal loss. Although cell losses were < 10% outside barriers, microglial activation with neuronal phagocytosis was detected. Downstream motor networks still generated locomotor activity 24 h later when stimulated with N-methyl-d-aspartate (NMDA) and serotonin, but not with repeated dorsal root stimuli. In the latter case, cumulative depolarization was recorded from ventral roots at a slower rate of rise, suggesting failure to recruit network premotoneurons. Our data indicate that, within the first 24 h of injury, locomotor networks below the lesion remained morphologically intact and functional when stimulated by NMDA and serotonin. Nevertheless, microglial activation and inability to produce locomotor patterns by dorsal afferent stimuli suggest important challenges to long-term network operation.
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