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Reduction in antioxidant enzyme expression and sustained inflammation enhance tissue damage in the subacute phase of spinal cord contusive injury.

ABSTRACT: BACKGROUND: Traumatic spinal cord injury (SCI) forms a disadvantageous microenvironment for tissue repair at the lesion site. To consider an appropriate time window for giving a promising therapeutic treatment for subacute and chronic SCI, global changes of proteins in the injured center at the longer survival time points after SCI remains to be elucidated. METHODS: Through two-dimensional electrophoresis (2DE)-based proteome analysis and western blotting, we examined the differential expression of the soluble proteins isolated from the lesion center (LC) at day 1 (acute) and day 14 (subacute) after a severe contusive injury to the thoracic spinal cord at segment 10. In situ apoptotic analysis was used to examine cell apoptosis in injured spinal cord after adenoviral gene transfer of antioxidant enzymes. In addition, administration of chondroitinase ABC (chABC) was performed to analyze hindlimb locomotor recovery in rats with SCI using Basso, Beattie and Bresnahan (BBB) locomotor rating scale. RESULTS: Our results showed a decline in catalase (CAT) and Mn-superoxide dismutase (MnSOD) found at day 14 after SCI. Accordingly, gene transfer of SOD was introduced in the injured spinal cord and found to attenuate cell apoptosis. Galectin-3, ?-actin, actin regulatory protein (CAPG), and F-actin-capping protein subunit ? (CAPZB) at day 14 were increased when compared to that detected at day 1 after SCI or in sham-operated control. Indeed, the accumulation of ?-actin+ immune cells was observed in the LC at day 14 post SCI, while most of reactive astrocytes were surrounding the lesion center. In addition, chondroitin sulfate proteoglycans (CSPG)-related proteins with 40-kDa was detected in the LC at day 3-14 post SCI. Delayed treatment with chondroitinase ABC (chABC) at day 3 post SCI improved the hindlimb locomotion in SCI rats. CONCLUSIONS: Our findings demonstrate that the differential expression in proteins related to signal transduction, oxidoreduction and stress contribute to extensive inflammation, causing time-dependent spread of tissue damage after severe SCI. The interventions by supplement of anti-oxidant enzymes right after SCI or delayed administration with chABC can facilitate spinal neural cell survival and tissue repair.

SUBMITTER: Wang CY

PROVIDER: S-EPMC3040708 | biostudies-other | 2011

REPOSITORIES: biostudies-other

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Reduction in antioxidant enzyme expression and sustained inflammation enhance tissue damage in the subacute phase of spinal cord contusive injury.

Wang Chih-Yen CY Chen Jen-Kun JK Wu Yi-Ting YT Tsai May-Jywan MJ Shyue Song-Kun SK Yang Chung-Shi CS Tzeng Shun-Fen SF

Journal of biomedical science 20110207

<h4>Background</h4>Traumatic spinal cord injury (SCI) forms a disadvantageous microenvironment for tissue repair at the lesion site. To consider an appropriate time window for giving a promising therapeutic treatment for subacute and chronic SCI, global changes of proteins in the injured center at the longer survival time points after SCI remains to be elucidated.<h4>Methods</h4>Through two-dimensional electrophoresis (2DE)-based proteome analysis and western blotting, we examined the differenti ...[more]

PMID: 21299884

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Project description:BackgroundThe anti-inflammatory cytokine interleukin-10 (IL-10) has been explored previously as a treatment method for spinal cord injury (SCI) due to its ability to attenuate pro-inflammatory cytokines and reduce apoptosis. Primary limitations when using systemic injections of IL-10 are that it is rapidly cleared from the injury site and that it does not cross the blood-spinal cord barrier.ObjectiveHere, mineral-coated microparticles (MCMs) were used to obtain a local sustained delivery of IL-10 directly into the injury site after SCI.MethodsFemale Sprague-Dawley rats were contused at T10 and treated with either an intraperitoneal injection of IL-10, an intramedullary injection of IL-10, or MCMs bound with IL-10 (MCMs+IL-10). After treatment, cytokine levels were measured in the spinal cord, functional testing and electrophysiology were performed, axon tracers were injected into the brainstem and motor cortex, macrophage levels were counted using flow cytometry and immunohistochemistry, and lesion size was measured.ResultsWhen treated with MCMs+IL-10, IL-10 was significantly elevated in the injury site and inflammatory cytokines were significantly suppressed, prompting significantly less cells expressing antigens characteristic of inflammatory macrophages and significantly more cells expressing antigens characteristic of earlier stage anti-inflammatory macrophages. Significantly more axons were preserved within the rubrospinal and reticulospinal tracts through the injury site when treated with MCMs+IL-10; however, there was no significant difference in corticospinal tract axons preserved, regardless of treatment group. The rats treated with MCMs+IL-10 were the only group with a significantly higher functional score compared to injured controls 28 days post-contusion.ConclusionThese data demonstrate that MCMs can effectively deliver biologically active IL-10 for an extended period of time altering macrophage phenotype and aiding in functional recovery after SCI.

Project description:The objective of this study was to conduct a systematic review of the literature to address the following clinical questions: In adult patients with acute and subacute complete or incomplete traumatic SCI, (1) does the time interval between injury and commencing rehabilitation affect outcome?; (2) what is the comparative effectiveness of different rehabilitation strategies, including different intensities and durations of treatment?; (3) are there patient or injury characteristics that affect the efficacy of rehabilitation?; and (4) what is the cost-effectiveness of various rehabilitation strategies?A systematic search was conducted for literature published through March 31, 2015 that evaluated rehabilitation strategies in adults with acute or subacute traumatic SCI at any level. Studies were critically appraised individually and the overall strength of evidence was evaluated using methods proposed by the GRADE (Grades of Recommendation Assessment, Development and Evaluation) working group.The search strategy yielded 384 articles, 19 of which met our inclusion criteria. Based on our results, there was no difference between body weight-supported treadmill training and conventional rehabilitation with respect to improvements in Functional Independence Measure (FIM) Locomotor score, Lower Extremity Motor Scores, the distance walked in 6 minutes or gait velocity over 15.2 m. Functional electrical therapy resulted in slightly better FIM Motor, FIM Self-Care, and Spinal Cord Independence Measure Self-Care subscores compared with conventional occupational therapy. Comparisons using the Toronto Rehabilitation Institute Hand Function Test demonstrated no differences between groups in 7 of 9 domains. There were no clinically important differences in Maximal Lean Test, Maximal Sidewards Reach Test, T-shirt Test, or the Canadian Occupational Performance Measure between unsupported sitting training and standard in-patient rehabilitation.The current evidence base for rehabilitation following acute and subacute spinal cord injury is limited. Methodological challenges have contributed to this and further research is still needed.

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Reduction in antioxidant enzyme expression and sustained inflammation enhance tissue damage in the subacute phase of spinal cord contusive injury.

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Reduction in antioxidant enzyme expression and sustained inflammation enhance tissue damage in the subacute phase of spinal cord contusive injury.

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