Soluble complement receptor type 1 inhibits complement system activation and improves motor function in acute spinal cord injury

Abstract

Study design: Spinal cord injured rat model, treated with soluble complement receptor type 1 (sCR1). Setting: Experimental Animal Department of China Medical University, Shenyang, China. Objectives: Soluble CR1 is a powerful inhibitor of complement activation. In this study, we investigate the effectiveness of sCR1 on spinal cord injury (SCI) in rats. Methods: Spinal cord injury was induced in Sprague-Dawley rats. Three experimental groups were examined; the sCR1 group was administered sCR1 at 1 h after the SCI, whereas the control group was administered saline at 1 h after SCI and the sham group underwent a sham operation without SCI or administration. The expressions of C9 and CD59 in the injured spinal cords were evaluated by immunohistochemistry, and numbers of positive cells counted. Furthermore, myeloperoxidase (MPO) activity and motor function were evaluated in each group. Results: At all postoperative time points, the numbers of C9-and CD59-positive cells in the sCR1 group were reduced compared with the control group and MPO activity was significantly decreased compared with both other groups. Moreover, the Basso, Beattie and Bresnahan score for the sCR1 group was significantly improved as compared with that of the control group after 7 days postoperatively. Conclusion: Soluble CR1 decreases inflammation reactions by inhibiting activation of the complement system and improves motor function after acute SCI.

Complement activation in the injured central nervous system: another dual-edged sword?

“…The effect of inhibiting the classical/alternative pathway [143] and C3b/C4b activity [144] was investigated in Sprague–Dawley rats subjected to moderate weight-drop SCI. In these studies, treated animals had decreased complement deposition and leukocyte infiltration, which was paralleled by increased tissue sparing and improved locomotor recovery compared to vehicle-treated animals subjected to SCI.…”

The alternative and terminal pathways of complement mediate post-traumatic spinal cord inflammation and injury

“…5 In other studies, complement inhibition at the C3 activation step with vaccinia virus complement control protein (VCP), 8 soluble CR1, 10 and a targeted form of Crry 7 were all protective against SCI and improved functional recovery. More recent studies have shown that C1q deficiency and C1-inhibitor are protective in models of SCI, 9,11 indicating an important role for the classical pathway.…”

“…Early studies showed that patients with spinal cord injury have elevated complement levels in their sera, 4 and more recent studies have used rodent models to demonstrate a role for complement in SCI. These studies include analysis of complement activation and deposition after SCI [5][6][7] and the demonstration that complement inhibition [7][8][9][10] or complement deficiency 7,11 ameliorates injury and improves functional recovery after traumatic injury.…”

Viral-derived complement inhibitors: current status and potential role in immunomodulation

“…166,167 Also in SCI, sCR1 decreased inflammatory reactions and improved motor function post-acute neurotrauma. 168 In a clinical trial of 59 lung transplant patients, the administration of TP-10, a soluble complement receptor 1 inhibitor, resulted in a decrease in the duration of mechanical ventilation compared to patients receiving a placebo. 169 Another clinical trial of 564 high-risk patients undergoing cardiac surgery showed that TP-10 reduced the incidence of mortality and MI particularly in male patients.…”