Journal of neurotrauma
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Journal of neurotrauma · Feb 2012
The antinociceptive effect of the asthma drug ibudilast in rat models of peripheral and central neuropathic pain.
Ibudilast, an asthma drug, has demonstrated antinociceptive effects in several rat models of peripheral neuropathic pain, and a proposed mechanism of action is the inhibition of release of the cytokine tumor necrosis factor-α (TNF-α) from activated spinal microglia. Spinal glial activation has also been demonstrated in rat models of central neuropathic pain following spinal cord injury (SCI). The current study evaluated the effect of a short course of treatment with ibudilast on SCI-induced pain, and for comparison, following a chronic constriction injury (CCI; the Bennett model) of the sciatic nerve in rats. ⋯ Ibudilast treatment did not significantly alter this increase. In rats with a CCI, TNF-α content was markedly increased in the ipsilateral sciatic nerve and was partially reduced following ibudilast, but not vehicle, treatment. Ibudilast could be useful for the treatment of neuropathic pain of central as well as peripheral origin.
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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.
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Journal of neurotrauma · Feb 2012
Deletion of the pro-apoptotic endoplasmic reticulum stress response effector CHOP does not result in improved locomotor function after severe contusive spinal cord injury.
Manipulation of various components of the endoplasmic reticulum (ER) stress response (ERSR) has led to functional recovery in diabetes, cancer, and several neurodegenerative diseases, indicating its use as a potential therapeutic intervention. One of the downstream pro-apoptotic transcription factors activated by the ERSR is CCAAT enhancer binding protein (C/EBP) homologous protein (CHOP). Recently, we showed significant recovery in hindlimb locomotion function after moderate contusive spinal cord injury (SCI) in mice null for CHOP. ⋯ Concomitantly, Basso Mouse Scale (BMS) scores and white matter sparing between the wild-type and CHOP-null mice revealed no significant differences. Given the complex pathophysiology of severe SCI, ablation of CHOP alone is not sufficient to rescue functional deficits. These data raise the caution that injury severity may be a key variable in attempting to translate preclinical therapies to clinical practice.
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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
A comprehensive subaxial cervical spine injury severity assessment model using numeric scores and its predictive value for surgical intervention.
Multiple factors contribute to the determination for surgical intervention in the setting of cervical spinal injury, yet to date no unified classification system exists that predicts this need. The goals of this study were twofold: to create a comprehensive subaxial cervical spine injury severity numeric scoring model, and to determine the predictive value of this model for the probability of surgical intervention. In a retrospective cohort study of 333 patients, neural impairment, patho-morphology, and available spinal canal sagittal diameter post-injury were selected as injury severity determinants. ⋯ The unit odds ratio for each determinant was 1.73, 1.61, and 1.45, for neural impairment, patho-morphology, and canal SD scores, respectively. The subaxial cervical spine injury severity determinants of neural impairment, patho-morphology, and post-injury available canal SD have well defined probability for surgical intervention when scored separately. Our data showed that each determinant alone could act as a primary predictor for surgical intervention.