Neuroprotective effects of the SCR_1–3 functional domain of CR1 on acute cerebral ischemia and reperfusion injury in rats

Abstract

Objective: Complement receptor type 1 (CR1), one of the most potent inhibitors in complement activation, shows a protective effect on cerebral ischemia/reperfusion (CI/R) injury due to its ability to bind C3b and C4b and to inactivate C3/C5 convertases. So far, no study assessed the effect of the first three short consensus repeats (SCR_1–3) with low molecular weight, one of the most active functional domains of CR1, binding C4b with a powerful decay-acceleration effect on classical and alternative C3/C5 convertases pathways. Therefore, we aim to assess this effect on CI/R injury in the present study.

Methods: Seventy-five adult male Sprague-Dawley rats were randomly divided into three groups: sham operation group (n  =  15), CI/R group (n  =  30), and CI/R group treated with CR1–SCR_1–3 protein (n  =  30). After middle cerebral artery occlusion (MCAO) for 1 hour and reperfusion for 24 hours, neurological motor deficits, cerebral infarct size, and biochemical parameters including myeloperoxidase (MPO), malondialdehyde (MDA), and superoxide dismutase (SOD) were assessed. Meanwhile, tissues in cerebral cortex were collected and processed for western blotting, immunohistochemistry, and HE staining.

Results: CR1–SCR_1–3 could improve neurological functions in brain with a 26·8% decrease in neurological motor deficit score and could lead to a 63·8% reduction in cerebral infarct size. Besides, pretreatment using CR1–SCR_1–3 could prevent neutrophil infiltration and alleviate inflammation severity and subsequent tissue damage. Decreased C4b expression and action, as well as improved morphological changes, were also observed in cerebral tissues of CI/R+CR1–SCR_1–3 rats.

Conclusion: CR1–SCR_1–3 protein could possess a neuroprotective effect on acute CI/R injury.

Keywords:

• Complement
• CR1
• SCR_1–3
• Inflammation
• Cerebral ischemia/reperfusion injury