Abstract

BackgroundThe complement system is a crucial mediator of inflammation and cell lysis after cerebral ischemia. However, there is little information about the exact contribution of the membrane attack complex (MAC) and its inhibitor-protein CD59.MethodsTransient focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in young male and female CD59a knockout and wild-type mice. Two models of MCAO were applied: 60 min MCAO and 48 h reperfusion, as well as 30 min MCAO and 72 h reperfusion. CD59a knockout animals were compared to wild-type animals in terms of infarct size, edema, neurological deficit, and cell death.Results and DiscussionCD59a-deficiency in male mice caused significantly increased infarct volumes and brain swelling when compared to wild-type mice at 72 h after 30 min-occlusion time, whereas no significant difference was observed after 1 h-MCAO. Moreover, CD59a-deficient mice had impaired neurological function when compared to wild-type mice after 30 min MCAO.ConclusionWe conclude that CD59a protects against ischemic brain damage, but depending on the gender and the stroke model used.

Highlights

  • The complement system is a crucial mediator of inflammation and cell lysis after cerebral ischemia

  • CD59a-deficiency increases infarct volume in mild experimental stroke, but not in the more severe stroke model First, we analysed whether CD59a-deficiency alters the size of the infarcted area in two different models of cerebral ischemia: a more severe stroke model (60 min occlusion time) and a mild one (30 min occlusion time)

  • When infarct volumes of male and female CD59adeficient mice and matching wild-type mice were compared after 1 h middle cerebral artery occlusion (MCAO) and 48 h of reperfusion, no significant difference between CD59a-knockout mice and wild-type mice, either in males (values are given as median [25th percentile, 75th percentile]: CD59am-/-: 108 mm3 [96 mm3, 164 mm3]; WTm: 129 mm3 [123 mm3, 144 mm3], in females (CD59af-/-: 129 mm3 [98 mm3, 145 mm3] WTf: 130 mm3 [109 mm3, 143 mm3], or in the mixed-gender group was detected (CD59amix-/-: 119 mm3 [94 mm3, 147 mm3] WTmix: 130 mm3 [113 mm3, 144 mm3]) (Figure 1A,C,E)

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Summary

Introduction

The complement system is a crucial mediator of inflammation and cell lysis after cerebral ischemia. The complement cascade is an important part of the innate immune system and is a potent mediator of inflammation and cell lysis which is activated following cerebral ischemia [5,6,7], and strong complement activation after ischemic stroke is associated with unfavourable outcomes [8]. The complement regulatory molecule CD59 represents the major controller of membrane attack complex (MAC) formation, and is an essential protector of homologous cells after complement mice [20]. This leads to the question whether CD59a may play a protective role in cerebral ischemia

Methods
Results
Conclusion

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