The secondary injury cascade after spinal cord injury:an analysis of local cytokine/chemokine regulation

After spinal cord injury,there is an extensive infiltration of immune cells,which exacerbates the injury and leads to further neural degeneration.Therefore,a major aim of current research involves targeting the immune response as a treatment for spinal cord injury.Although much research has been performed analyzing the complex inflammatory process following spinal cord injury,there remain major discrepancies within previous literature regarding the timeline of local cytokine regulation.The objectives of this study were to establish an overview of the timeline of cytokine regulation for 2 weeks after spinal cord injury,identify sexual dimorphisms in terms of cytokine levels,and determine local cytokines that significantly change based on the severity of spinal cord injury.Rats were inflicted with either a mild contusion,moderate contusion,severe contusion,or complete transection,7 mm of spinal cord centered on the injury was harvested at varying times post-injury,and tissue homogenates were analyzed with a Cytokine/Chemokine 27-Plex assay.Results demonstrated pro-inflammatory cytokines including tumor necrosis factorα,interleukin-1β,and interleukin-6 were all upregulated after spinal cord injury,but returned to uninjured levels within approximately 24 hours post-injury,while chemokines including monocyte chemoattractant protein-1 remained upregulated for days post-injury.In contrast,several anti-inflammatory cytokines and growth factors including interleukin-10 and vascular endothelial growth factor were downregulated by 7 days post-injury.After spinal cord injury,tissue inhibitor of metalloproteinase-1,which specifically affects astrocytes involved in glial scar development,increased more than all other cytokines tested,reaching 26.9-fold higher than uninjured rats.After a mild injury,11 cytokines demonstrated sexual dimorphisms;however,after a severe contusion only leptin levels were different between female and male rats.In conclusion,pro-inflammatory cytokines initiate the inflammatory process and return to baseline within hours post-injury,chemokines continue to recruit immune cells for days post-injury,while anti-inflammatory cytokines are downregulated by a week post-injury,and sexual dimorphisms observed after mild injury subsided with more severe injuries.Results from this work define critical chemokines that influence immune cell infiltration and important cytokines involved in glial scar development after spinal cord injury,which are essential for researchers developing treatments targeting secondary damage after spinal cord injury.

Gait analysis in swine,sheep,and goats after neurologic injury:a literature review

Medical research on neurologic ailments requires representative animal models to validate treatments before they are translated to human clinical trials.Rodents are the predominant animal model used in neurological research despite limited anatomic and physiologic similarities to humans.As a result,functional testing designed to assess locomotor recovery after neurologic impairment is well established in rodent models.Comparatively,large r,more clinically relevant models have not been as well studied.To achieve similar locomotor testing standardization in larger animals,the models must be accessible to a wide array of researchers.Non-human primates are the most relevant animal model fo r translational research,however ethical and financial barriers limit their accessibility.This review focuses on swine,sheep,and goats as large animal alternatives for transitional studies between rodents and non-human primates.The objective of this review is to compare motor testing and data collection methods used in swine,sheep,and goats to encourage testing standardization in these larger animal models.The PubMed database was analyzed by searching combinations of swine,sheep,and goats,neurologic injuries,and functional assessments.Findings were categorized by animal model,data collection method,and assessment design.Swine and sheep were used in the majority of the studies,while only two studies were found using goats.The functional assessments included open pen analysis,treadmill walking,and guided free walking.Data collection methods included subjective behavioral rating scales and objective tools such as pressure-sensitive mats and image-based analysis software.Overall,swine and sheep were well-suited for a variety of assessment designs,with treadmill walking and guided free walking offering the most consistency across multiple trials.Data collection methods varied,but image-based gait analysis software provided the most robust analysis.Future studies should be conducted to standardize functional testing methods after neurologic impairment in large animals.