Journal of neurotrauma
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Journal of neurotrauma · Feb 2012
Chronic spinal compression model in minipigs: a systematic behavioral, qualitative, and quantitative neuropathological study.
The goal of the present study was to develop a porcine spinal cord injury (SCI) model, and to describe the neurological outcome and characterize the corresponding quantitative and qualitative histological changes at 4-9 months after injury. Adult Gottingen-Minnesota minipigs were anesthetized and placed in a spine immobilization frame. The exposed T12 spinal segment was compressed in a dorso-ventral direction using a 5-mm-diameter circular bar with a progressively increasing peak force (1.5, 2.0, or 2.5 kg) at a velocity of 3 cm/sec. ⋯ In fully paralyzed animals (2.5 kg), MRI analysis demonstrated a loss of spinal white matter integrity and extensive septal cavitations. A significant correlation between the magnitude of loss of small and medium-sized myelinated axons in the ventral funiculus and neurological deficits was identified. These data, demonstrating stable neurological deficits in severely injured animals, similarities of spinal pathology to humans, and relatively good post-injury tolerance of this strain of minipigs to spinal trauma, suggest that this model can successfully be used to study therapeutic interventions targeting both acute and chronic stages of SCI.
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Journal of neurotrauma · Feb 2012
Conservatively treated ossification of the posterior longitudinal ligament increases the risk of spinal cord injury: a nationwide cohort study.
The optimal treatment strategy for ossification of the posterior longitudinal ligament (OPLL) depends on symptoms and is uncertain. Whether the risk of spinal cord injury (SCI) is increased in patients with cervical spinal stenosis or myelopathy caused by OPLL remains unclear. This study aimed to evaluate the risk of SCI in patients with OPLL of the cervical spine when managed with conservative treatment (no surgery). ⋯ After adjustments, the OPLL group had a 32.16-fold (p<0.001) higher risk for cervical SCI. Disability caused by SCI had an even higher risk (HR=110.72, adjusted HR=104.78; p<0.001) for the OPLL group. Therefore, cervical SCI and related disabilities are more likely to happen in OPLL patients, who should be cautioned for subsequent SCI if treated conservatively.
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Journal of neurotrauma · Feb 2012
Docosahexaenoic acid pretreatment confers protection and functional improvements after acute spinal cord injury in adult rats.
Currently, few interventions have been shown to successfully limit the progression of secondary damage events associated with the acute phase of spinal cord injury (SCI). Docosahexaenoic acid (DHA, C22:6 n-3) is neuroprotective when administered following SCI, but its potential as a pretreatment modality has not been addressed. This study used a novel DHA pretreatment experimental paradigm that targets acute cellular and molecular events during the first week after SCI in rats. ⋯ DHA pretreatment induced levels of Akt and cyclic AMP responsive element binding protein (CREB) mRNA and protein. This study shows for the first time that DHA pretreatment ameliorates functional deficits, and increases tissue sparing and precursor cell survival. Further, our data suggest that DHA-mediated activation of pro-survival/anti-apoptotic pathways may be independent of its anti-inflammatory effects.
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Journal of neurotrauma · Feb 2012
Paranodal myelin damage after acute stretch in Guinea pig spinal cord.
Mechanical injury causes myelin disruption and subsequent axonal conduction failure in the mammalian spinal cord. However, the underlying mechanism is not well understood. In mammalian myelinated axons, proper paranodal myelin structure is crucial for the generation and propagation of action potentials. ⋯ Decompaction of paranodal myelin was also observed. It was shown that paranodal demyelination can result from both an initial physical impact and secondary biochemical reactions that are calcium dependent. 4-Aminopyridine (4-AP), a known potassium channel blocker, can partially restore axonal conduction, which further implicates the role of potassium channels in conduction failure. We provide important evidence of paranodal myelin damage, the role of potassium channels in conduction loss, and the therapeutic value of potassium blockade as an effective intervention to restore function following spinal cord trauma.
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Journal of neurotrauma · Feb 2012
Functional recovery, serotonergic sprouting, and endogenous progenitor fates in response to delayed environmental enrichment after spinal cord injury.
Environmental enrichment (EE) is a way to induce voluntary locomotor training that positively affects locomotor recovery after acute spinal cord injury (SCI). The beneficial effect on SCI outcome is thought to be based on enhanced plasticity in motor pathways, triggered by locomotor-specific sensory feedback to the spinal cord circuitry for locomotion (central pattern generators [CPGs]). In view of chronic SCI, we tested the hypothesis that EE improves motor outcome after SCI in the rat when started after a clinically relevant delay of 3 weeks. ⋯ Although spinal cord progenitor cells were found to differentiate into both neurons and glial cells, EE did not affect their survival. These results show that EE induces a substantial improvement of motor outcome after SCI when commenced after a clinically-relevant delay. Increased serotonergic innervation of the lumbar CPG area is therefore suggested to play an important role in the EE-induced recovery of interlimb coordination.