Journal of neurotrauma
-
Journal of neurotrauma · Sep 2019
Novel speed-controlled automated ladder walking device reveals walking speed as a critical determinant of skilled locomotion after a spinal cord injury in adult rats.
The horizontal ladder task is an established method to assess skilled locomotor recovery after neurological dysfunction. Walking speed is often used as a standardized measure in locomotor assessment of overground walking in human and pre-clinical studies, but the assessment of walking speed is typically ignored during skilled locomotor tasks. Ample empirical evidence indicates that walking speeds on the horizontal ladder are largely non-uniform after central nervous system trauma, suggesting that it could pose a potential source of variability in assessing motor deficits. ⋯ The ADATS allows testing at user-defined speeds, thereby forcing the rats to step consistently. Our results demonstrate that: 1) the ability to walk (or not) at one or multiple speeds on the ADATS serves as a gross measure of motor dysfunction/recovery after a spinal cord injury and 2) skilled motor deficits are more readily detected at lower than higher walking speeds. We conclude that walking speed is an important factor in the analyses of skilled locomotion and testing at multiple speeds is useful in accurately measuring recovery after neurotrauma in rats.
-
Journal of neurotrauma · Sep 2019
Multicenter Study Observational StudyUnbiased Recursive Partitioning to Stratify Patients With Acute Traumatic Spinal Cord Injuries: External Validity in an Observational Cohort Study.
Clinical trials of novel therapies for acute spinal cord injury (SCI) are challenging because variability in spontaneous neurologic recovery can make discerning actual treatment effects difficult. Unbiased Recursive Partitioning regression with Conditional Inference Trees (URP-CTREE) is a novel approach developed through analyses of a large European SCI database (European Multicenter Study about Spinal Cord Injury). URP-CTREE uses early neurologic impairment to predict achieved motor recovery, with potential to optimize clinical trial design by optimizing patient stratification and decreasing sample sizes. ⋯ A previous URP-CTREE model had limited ability to stratify an independent into homogeneous subgroups. Overall accuracy was promising, but may be sensitive to timing of baseline neurological examinations. Further evaluation of external validity in incomplete injuries, influence of timing of baseline examinations, and investigation of additional stratification strategies is warranted.
-
Journal of neurotrauma · Sep 2019
Bisperoxovanadium mediates neuronal protection through inhibition of PTEN and activation of PI3K/AKT-mTOR signaling following traumatic spinal injuries.
Although mechanisms involved in progression of cell death in spinal cord injury (SCI) have been studied extensively, few are clear targets for translation to clinical application. One of the best-understood mechanisms of cell survival in SCI is phosphatidylinositol-3-kinase (PI3K)/Akt and associated downstream signaling. Clear therapeutic efficacy of a phosphatase and tensin homologue (PTEN) inhibitor called bisperoxovanadium (bpV) has been shown in SCI, traumatic brain injury, stroke, and other neurological disease models in both neuroprotection and functional recovery. ⋯ Conversely, PTEN activity appeared to increase over this period. As observed in vitro, bpV also increased Erk activity post-SCI (p < 0.05). Our results suggest that PI3K/Akt signaling is the likely primary mechanism of bpV action in mediating neuroprotection in injured spinal neurons.
-
We previously reported the serendipitous observation that fenbendazole, a benzimidazole anthelmintic, improved functional and pathological outcomes following thoracic spinal cord contusion injury in mice when administered pre-injury. Fenbendazole is widely used in veterinary medicine. However, it is not approved for human use and it was uncertain if only post-injury administration would offer similar benefits. ⋯ Histological analysis of spinal cord sections showed that such treatment with flubendazole also reduced lesion volume and improved total tissue sparing, white matter sparing, and gray matter sparing. Flubendazole inhibited the activation of glial fibrillary acidic protein (GFAP); suppressed cyclin B1 expression and Bruton tyrosine kinase activation, markers of B cell activation/proliferation and inflammation; and reduced B cell autoimmune response. Together, these results suggest the use of the benzimidazole anthelmintic flubendazole as a potential therapeutic for SCI.
-
Journal of neurotrauma · Sep 2019
An accurate method for histological determination of neural tissue loss/sparing following compression-induced spinal cord injury with optimal reproducibility.
In addition to behavioral testing, the efficacy of neuroprotective therapies applied after spinal cord injury (SCI) is commonly evaluated by means of histological quantification of spared neural tissue. The primary insult itself, but mainly the pathological processes of secondary injury are the underlying causes of spinal tissue degeneration, the extent of which depends on the injury severity and post-injury time. ⋯ To overcome the problem, our new quantification approach combines a modified method for predicting the cross-sectional area at the lesion site with semi-automatic measurement of spared neural tissue and cystic cavities, using freely accessible National Institutes of Health (NIH) ImageJ software, with a Java-based image processing program. Based on the histological parameters measured after differing compression-induced SCI and correlated with behavioral outcomes, we can conclude that our new method is relatively fast, accurate, and optimally reproducible.