Journal of neurotrauma
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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
Multicenter StudyComputer implementation of the international standards for neurological classification of spinal cord injury for consistent and efficient derivation of its subscores including handling of data from not testable segments.
The International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), defined by the American Spinal Injury Association (ASIA), and particularly the ASIA Impairment Scale (AIS) are widely used for research and clinical purposes. Although detailed procedures for scaling, scoring, and classification have been defined, misclassifications remain a major problem, especially for cases with missing (i.e., not testable [NT]) data. This work aimed to implement computer-based classification algorithms that included rules for handling NT data. ⋯ Additionally, the computational method is much more efficient, processing approximately 200,000 classifications/sec. Computational algorithms offer the ability to classify ISNCSCI subscores efficiently and without the risk of human-induced errors. This is of particular clinical relevance, since these scores are used for early predictions of neurological recovery and functional outcome for patients with spinal cord injuries.
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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.
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Journal of neurotrauma · Feb 2012
Delayed anti-nogo-a antibody application after spinal cord injury shows progressive loss of responsiveness.
Blocking the function of the myelin protein Nogo-A or its signaling pathway is a promising method to overcome an important neurite growth inhibitory factor of the adult central nervous system (CNS), and to enhance axonal regeneration and plasticity after brain or spinal cord injuries. Several studies have shown increased axonal regeneration and enhanced compensatory sprouting, along with substantially improved functional recovery after treatment with anti-Nogo-A antibodies, Nogo-receptor antagonists, or inhibition of the downstream mediator RhoA/ROCK in adult rodents. Proof-of-concept studies in spinal cord-injured macaque monkeys with anti-Nogo-A antibodies have replicated these findings; recently, clinical trials in spinal cord-injured patients have begun. ⋯ We found that lesioned CST fibers regenerated over several millimeters after acute or 1-week-delayed treatments, but not when the antibody treatment was started with a delay of 2 weeks. Swimming and narrow beam crossing recovered well in rats treated acutely or with a 1-week delay with anti-Nogo-A antibodies, but not in the 2-week-delayed group. These results show that the time frame for treatment of spinal cord lesions with anti-Nogo-A antibodies is restricted to less than 2 weeks in adult rodents.
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Journal of neurotrauma · Feb 2012
CD11d Antibody Treatment Improves Recovery in Spinal Cord-Injured Mice.
Acute administration of a monoclonal antibody (mAb) raised against the CD11d subunit of the leukocyte CD11d/CD18 integrin after spinal cord injury (SCI) in the rat greatly improves neurological outcomes. This has been chiefly attributed to the reduced infiltration of neutrophils into the injured spinal cord in treated rats. More recently, treating spinal cord-injured mice with a Ly-6G neutrophil-depleting antibody was demonstrated to impair neurological recovery. ⋯ The anti-CD11d treatment reduced neutrophil infiltration into the injured mouse spinal cord and was associated with increased white matter sparing and reductions in myeloperoxidase (MPO) activity, reactive oxygen species, lipid peroxidation, and scar formation. These improvements in the injured spinal cord microenvironment were accompanied by increased serotonin (5-HT) immunoreactivity below the level of the lesion and improved locomotor recovery. Our results with the 205C CD11d mAb treatment complement previous work using this anti-integrin treatment in a rat model of SCI.