Expression of C5a and its receptor following spinal cord ischemia reperfusion injury in the rat

Abstract

Study design: Experimental study. Objective: To investigate the expression of C5a and its receptor after spinal cord ischemia reperfusion injury (SIRI) in rat. Setting: Department of Neurosurgery, the Second Affiliated Hospital, Xi'an Jiaotong University, Shaanxi Province, Xi'an, China Methods: Sprague Dawley rats were subjected to 1 h of infrarenal aorta occlusion to induce spinal cord ischemia. Spinal cord was reperfused for 12, 24, 48 h or 3 days separately after ischemia, respectively. Enzyme-linked immunosorbent assay was used to detect C5a in rat serum. Immunofluorescent staining was performed to detect the expression and cellular localization of C5aR in spinal cord following SIRI. Results: Following SIRI, the motor behavior of the rats was significantly compromised. The serum concentration of C5a in the rat was elevated after SIRI and peaked at 24 h. C5aR was significantly upregulated in the lumbar spinal cord following SIRI and expressed on motor neurons and the microglia, but not astrocyte. There was no significant difference in the expression level of C5aR localized on motor neurons after SIRI. Remarkable upregulation of the C5aR may be associated with increased number of C5aR-positive microglia and elevated cellular expression level. Conclusion: This study provides the first evidence of the expression of C5a and its receptors in SIRI and suggests their possible contribution to SIRI in a rat model.

Osteoblast-specific overexpression of complement receptor C5aR1 impairs fracture healing

“…We previously demonstrated that osteoblasts strongly upregulated C5aR1 during the early phase after bone fracture [1]. Therefore, we hypothesized, that C5a, which is known to be abundantly generated locally and systemically in response to tissue injury [32–34], may induce an immune-modulatory response in osteoblasts during fracture healing. Our results revealed that the concentration of IL-6, a key cytokine in the local immune response after bone fracture and in posttraumatic systemic inflammation [35–38], was neither locally nor systemically altered in Col1a1-C5aR1 mice.…”

Blood-spinal cord barrier disruption in degenerative cervical myelopathy

“…Compounds derived from natural herbs that possess anti-inflammatory or antioxidant activity, such as shikonin, curcumin, and salvianolic acid B have also demonstrated efficacy in rat models of SCI [ 205 – 208 ]. Arachidonic acid pathway attenuation [ 209 – 211 ], monoacylglycerol lipase (MAGL) inhibition [ 212 , 213 ], and inhibition of complement C5a [ 214 – 216 ] are also potential pharmacological targets as alternatives to more established anti-inflammatory agents such as corticosteroids, riluzole, and NSAIDs.…”