Inflammation Level after Decompression Surgery for a Rat Model of Chronic Severe Spinal Cord Compression and Effects on Ischemia-Reperfusion Injury

Abstract

Delayed neurological deterioration in the absence of direct spinal cord insult following surgical decompression is a severe postoperative complication in patients with chronic severe spinal cord compression (SCC). The spinal cord ischemia-reperfusion injury (IRI) has been verified as a potential etiology of the complication. However, the exact pathophysiologic mechanisms of the decompression-related IRI remain to be defined. In this study, we developed a practical rat model of chronic severe SCC. To explore the underlying role of inflammation in decompression-related IRI, immunoreactivity of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) before and after decompression were measured. In addition, expression level of TNF-α and IL-1β was examined with Western blot. Immunohistochemical staining showed negative result in gray matters in the sham group and sham-decompression group. In the severe compression group, strong positive staining of TNF-α and IL-1β were found, suggesting a dramatic infiltration of inflammatory cells in gray matters. Furthermore, the severe compression group showed a significant increase in expression level of TNF-α and IL-1β as compared with the sham group (p < 0.05). In the severe compression-decompression group, both immunostaining and Western blot showed significant increase of TNF-α and IL-1β levels in the spinal cord compared with the severe compression group (p < 0.05). The results demonstrated that surgical decompression plays a stimulative role in inflammation through increasing the expression of inflammatory cytokines in the rat model of chronic severe SCC injury. Inflammation may be one of the important pathological mechanisms of decompression-related IRI of chronic ischemia.

Fig. 1

Magnetic resonance imaging after chronic severe spinal cord compression. a: The severe compression material was located dorsally within the spinal canal at the T8–9 levels on sagittal T₂-weighted images. b: The sheet compressed the spinal cord severely and the invasion ratio of the spinal canal was over 70%, which was measured on axial T₂-weighted images.

Fig. 2

Immunohistochemical localizations of tumor necrosis factor-alpha (TNF-α) in spinal cord in sham group (a), sham-decompression (sham-d) group (b), severe compression (SC) group (c), and severe compression-decompression (SC-d) (d) (original magnification ×40). No obvious positive staining of TNF-α was observed in sham group and sham-d group (^*p > 0.05); a substantial increase in the release of TNF-α was found in various cells in the SC group compared with the sham group (^**p < 0.05); whereas TNF-α production increased significantly in the SC-d group compared with the SC group (^#p < 0.05) (e).

Fig. 3

Immunohistochemical localizations of interleukin-1β (IL-1β) in spinal cord in sham group (a), sham-decompression (sham-d) group (b), severe compression (SC) group (c), and severe compression-decompression (SC-d) (d) (original magnification ×40). No obvious positive staining of IL-1β was observed in sham group and sham-d group (^*p > 0.05); a substantial increase in the release of IL-1β was found in various cells in the SC group compared with the sham group (^**p < 0.05); whereas IL-1β production increased significantly in the SC-d group compared with the SC group (^#p < 0.05) (e).

Fig. 4

Expression levels of pro-inflammatory cytokines in the four groups. No difference was observed between the sham and sham-decompression groups (^*p > 0.05) (a). Severe compression resulted in higher level of tumor necrosis factor-alpha (TNF-α) in the spinal cord compared with the sham group (^**p < 0.05). Meanwhile, decompression surgery substantially elevated TNF-α levels in the decompression group compared with the compression group (^#p < 0.05). The levels of TNF-α were measured by Western blot analysis using actin as a standard control. No difference was observed between the sham and sham-decompression groups (^*p > 0.05) (b). Severe compression resulted in higher level of interleukin-1β (IL-1β) levels compared with the sham group (^**p < 0.05). Meanwhile, decompression surgery substantially elevated IL-1β levels in the decompression group compared with the compression group (^#p < 0.05). The levels of IL-1β were measured by Western blot analysis using actin as a standard control.