Dataset Information

Metabolite profiles correlate closely with neurobehavioral function in experimental spinal cord injury in rats.

ABSTRACT: Traumatic spinal cord injury (SCI) results in direct physical damage and the generation of local factors contributing to secondary pathogenesis. Untargeted metabolomic profiling was used to uncover metabolic changes and to identify relationships between metabolites and neurobehavioral functions in the spinal cord after injury in rats. In the early metabolic phase, neuronal signaling, stress, and inflammation-associated metabolites were strongly altered. A dynamic inflammatory response consisting of elevated levels of prostaglandin E2 and palmitoyl ethanolamide as well as pro- and anti-inflammatory polyunsaturated fatty acids was observed. N-acetyl-aspartyl-glutamate (NAAG) and N-acetyl-aspartate (NAA) were significantly decreased possibly reflecting neuronal cell death. A second metabolic phase was also seen, consistent with membrane remodeling and antioxidant defense response. These metabolomic changes were consistent with the pathology and progression of SCI. Several metabolites, including NAA, NAAG, and the ?-3 fatty acids docosapentaenoate and docosahexaenoate correlated greatly with the established Basso, Beattie and Bresnahan locomotive score (BBB score). Our findings suggest the possibility of a biochemical basis for BBB score and illustrate that metabolites may correlate with neurobehavior. In particular the NAA level in the spinal cord might provide a meaningful biomarker that could help to determine the degree of injury severity and prognosticate neurologic recovery.

SUBMITTER: Fujieda Y

PROVIDER: S-EPMC3418274 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Metabolite profiles correlate closely with neurobehavioral function in experimental spinal cord injury in rats.

Fujieda Yusuke Y Ueno Shinya S Ogino Ryoko R Kuroda Mariko M Jönsson Thomas J TJ Guo Lining L Bamba Takeshi T Fukusaki Eiichiro E

PloS one 20120813 8

Traumatic spinal cord injury (SCI) results in direct physical damage and the generation of local factors contributing to secondary pathogenesis. Untargeted metabolomic profiling was used to uncover metabolic changes and to identify relationships between metabolites and neurobehavioral functions in the spinal cord after injury in rats. In the early metabolic phase, neuronal signaling, stress, and inflammation-associated metabolites were strongly altered. A dynamic inflammatory response consisting ...[more]

PMID: 22912814

Similar Datasets

Project description:BackgroundThere is emerging evidence that astaxanthin plays a significant role in protecting neuro-cells from apoptosis after central nervous system injury. Our study examined the effects of astaxanthin on neuro-cell apoptosis after spinal cord injury.MethodsOne hundred and forty-four healthy adult Sprague-Dawley rats were randomly divided into the experimental group, control group, and sham operation group (n=48). Spinal cord injury was induced using the modified Allen method in the control group and the experimental group; while in the sham operation group, the lamina was removed without spinal cord injury. The rats in the experimental group were given astaxanthin (75 mg/kg) by gavage immediately after the operation, and in the other groups were given the same amount of olive oil. Motor function was assessed by blood-brain barrier (BBB) scores. The malondialdehyde (MDA) content and the activity of superoxide dismutase (SOD) at 24 h was determined after the operation. The apoptosis index (AI) was determined at 6, 24, and 48 h after the operation. At 48 h after the operation, we calculated the water content of the spinal cord, the lesion ratio of the spinal cord, the ultrastructure of the spinal cord, and the ultrastructure score.ResultsThe BBB scores of the control and experimental groups were significantly lower than the sham operation group at each postoperative time (P<0.05), and the BBB score of the experimental group was significantly higher than the control group at 1-4 weeks postoperatively (P<0.05). At 24 hours postoperatively, MDA content was highest in the control group and lowest in the sham operation group, while SOD activity was highest in the sham operation group and lowest in the control group (P<0.05). At each time point postoperatively, the sham operation group had the lowest AI and the control group had the highest AI (P<0.05). At 48 h after the operation, the water content and the lesion ratio of the spinal cord, and the ultrastructure score were the lowest in the sham operation group and the highest in the control group (P<0.05).ConclusionsAstaxanthin significantly improved the motor function of rats with spinal cord injury.

Project description:Background: Traumatic spinal cord injury (t-SCI) is a severe injury that has a devastating impact on neurological function. Blood spinal cord barrier (BSCB) destruction following SCI aggravates the primary injury, resulting in a secondary injury. A series of experimental treatments have been proven to alleviate BSCB destruction after t-SCI. Methods: From a screen of 1,189 papers, which were retrieved from Pubmed, Embase, and Web of science, we identified 28 papers which adhered to strict inclusion and exclusion criteria. Evans blue (EB) leakage on the first day post-SCI was selected as the primary result. Secondary outcomes included the expression of tight junction (TJ) proteins and adhesion junction (AJ) proteins in protein immunoblotting. In addition, we measured functional recovery using the Basso, Beattie, Besnahan (BBB) score and we analyzed the relevant mechanisms to explore the similarities between different studies. Result: The forest plot of Evans blue leakage (EB leakage) reduction rate: the pooled effect size of the 28 studies was 0.54, 95% CI: 0.47–0.61, p < 0.01. This indicates that measures to mitigate BSCB damage significantly improved in reducing overall EB leakage. In addition TJ proteins (Occludin, Claudin-5, and ZO-1), AJ proteins (P120 and β-catenin) were significantly upregulated after treatment in all publications. Moreover, BBB scores were significantly improved. Comprehensive studies have shown that in t-SCI, inhibition of matrix metalloproteinases (MMPs) is the most commonly used mechanism to mitigate BSCB damage, followed by endoplasmic reticulum (ER) stress and the Akt pathway. In addition, we found that bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos), which inhibit the TIMP2/MMP signaling pathway, may be the most effective way to alleviate BSCB injury. Conclusion: This study systematically analyzes the experimental treatments and their mechanisms for reducing BSCB injury in the early stage of t-SCI. BMSC-Exos, which inhibit MMP expression, are currently the most effective therapeutic modality for alleviating BSCB damage. In addition, the regulation of MMPs in particular as well as the Akt pathway and the ER stress pathway play important roles in alleviating BSCB injury. Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022324794.

Dataset Information

Metabolite profiles correlate closely with neurobehavioral function in experimental spinal cord injury in rats.

Publications

Metabolite profiles correlate closely with neurobehavioral function in experimental spinal cord injury in rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets