Chronic spinal cord changes in a high-fat diet-fed male rat model of thoracic spinal contusion

Abstract

Individuals that suffer injury to the spinal cord can result in long-term, debilitating sequelae. Spinal cord-injured patients have increased risk for the development of metabolic disease, which can further hinder the effectiveness of treatments to rehabilitate the cord and improve quality of life. In the present study, we sought to understand the impact of high-fat diet (HFD)-induced obesity on spinal cord injury (SCI) by examining transcriptome changes in the area of the injury and rostral and caudal to site of damage 12 wk after injury. Adult, male Long-Evans rats received either thoracic level contusion of the spinal cord or sham laminectomy and then were allowed to recover on normal rat chow for 4 wk and further on HFD for an additional 8 wk. Spinal cord tissues harvested from the rats were processed for Affymetrix microarray and further transcriptomic analysis. Diverse changes in gene expression were identified in the injured cord in genes such as MMP12, APOC4, GPNMB, and IGF1 and 2. The greatest signaling changes occurred in pathways involved in cholesterol biosynthesis and immune cell trafficking. Together, the cord changes in the chronically obese rat following thoracic SCI reveal further potential targets for therapy. These could be further explored as they overlap with genes involved in metabolic disease.

Energy balance following diets of varying fat content: metabolic dysregulation in a rodent model of spinal cord contusion

“…Still others have directly administered SCI rodents with omega‐3 or −6 fatty acids in hope of enhancing neuroprotection following injury (King et al ; Lim et al ). To our knowledge, our previous microarray study was the first study where tSCI animals were placed on a western‐style, high‐fat, high‐carbohydrate diet chronically (8 weeks) to exacerbate metabolic dysfunction, and obesity (Spann et al ). In the current study, we again utilized this western‐style HFD but also in parallel, expanded the study to include a control LFD; we extended use of the diet to a total of 12 weeks to maximize its effects.…”

A Western diet impairs CNS energy homeostasis and recovery after spinal cord injury: Link to astrocyte metabolism

“…Experimental obesity also exacerbates neuroinflammation in the experimental autoimmune encephalomyelitis model of MS ( Ji et al, 2019 ; Timmermans et al, 2014 ) and after experimental TBI ( Hoane et al, 2011 ; Karelina et al, 2016 ; Sherman et al, 2016 ; Tyagi et al, 2013 ). There is much more limited information regarding the impact of obesity in models of SCI; however, transcriptional analysis points to perturbed spinal cord metabolism ( Spann et al, 2017 ), and recent studies also suggest reductions in functional recovery after injury ( Harris et al, 2019 ). Given the high risk for the development of metabolic syndrome after SCI and its role as a significant co-morbidity, we investigated the impact of Western diet-induced obesity on metabolic function and energy homeostasis in the adult mouse spinal cord and its response to traumatic injury, including the capacity for repair.…”

Immune and Metabolic Biomarkers in a Rodent Model of Spinal Cord Contusion

“…Thoracic-level tissues were dissected 1.5 cm around the thoracic enlargement as depicted ( Figure 1C ) and used for primary gene expression analyses that were prioritized based on immune and lipid metabolism functions as described previously. 12 Our generalized scheme was to further distill previous microarray gene targets, validate their expression at 2 time points, perform secondary linear regression with key clinical features, and measure top candidates in circulation at 4 and 16 weeks postinjury ( Figure 1D ).…”

“…Among the differentially regulated genes identified, 12 there was a robust representation of lipid/cholesterol-related genes. We focused on some targets which were promising candidates.…”

“…Here, we exploit our previously published microarray data 12 to determine whether the immune and metabolic markers we identified in the thoracic cord using a moderate T10 contusion model may become viable biomarkers for the progression of clinical features. We couple quantitative real-time polymerase chain reaction (PCR) of the thoracic region of the cord with blood samples from 2 cohorts of animals.…”