Abstract
BackgroundTraumatic 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.MethodsThrough 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.ResultsOur 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, β-actin, actin regulatory protein (CAPG), and F-actin-capping protein subunit β (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 β-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.ConclusionsOur 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.
Highlights
Traumatic spinal cord injury (SCI) forms a disadvantageous microenvironment for tissue repair at the lesion site
No significant difference in the intensity of peroxiredoxin 1(Prx1; spot 73 and 75) and Prx6 was seen in the lesion center (LC) between day 1 and day 14 (Table 3), western blot analysis showed that these proteins were time-dependently reduced post SCI (Figure 2A)
In consistence with the findings described as above, we have shown that cathepsin D (CATD) was about 23-fold increased in the LC at day 14 SCI when compared to that detected at day 1 after SCI (Table 1)
Summary
Traumatic spinal cord injury (SCI) forms a disadvantageous microenvironment for tissue repair at the lesion site. Traumatic spinal cord injury (SCI) causes permanent paralysis in patients due to low regeneration of the CNS [1]. The events occurring immediately after SCI include neuronal fiber damage, mass ischemic neural cell necrosis and apoptosis, metabolic disturbances, the destruction of microvasculature, inflammation, lipid peroxidation, free radical production, demyelination, and glial scar formation, leading to extensive secondary tissue injuries [1,2,3]. In response to local inflammation after SCI, microglia, CNS-resident macrophages, are activated, which trigger inflammatory reaction in the injured center [2,5]. The scar tissue contains the inhibitors to axon outgrowth, producing a microenvironment that is not beneficial for tissue repair after SCI [1,9,10]
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