Mannose-binding lectin promotes local microvascular thrombosis after transient brain ischemia in mice

Stroke. 2014 May;45(5):1453-9. doi: 10.1161/STROKEAHA.113.004111. Epub 2014 Mar 27.


Background and purpose: Several lines of evidence support the involvement of mannose-binding lectin (MBL) in stroke brain damage. The lectin pathway of the complement system facilitates thrombin activation and clot formation under certain experimental conditions. In the present study, we examine whether MBL promotes thrombosis after ischemia/reperfusion and influences the course and prognosis of ischemic stroke.

Methods: Middle cerebral artery occlusion/reperfusion was performed in MBL-deficient (n=85) and wild-type (WT; n=83) mice, and the brain lesion was assessed by MRI at days 1 and 7. Relative cerebral blood flow was monitored up to 6 hours after middle cerebral artery occlusion with laser speckle contrast imaging. Fibrin(ogen) was analyzed in the brain vasculature and plasma, and the effects of thrombin inhibitor argatroban were evaluated to assess the role of MBL in thrombin activation.

Results: Infarct volumes and neurological deficits were smaller in MBL knockout mice than in WT mice. Relative cerebral blood flow values during middle cerebral artery occlusion and at reperfusion were similar in both groups, but decreased during the next 6 hours in the WT group only. Also, the WT mice showed more fibrin(ogen) in brain vessels and a better outcome after argatroban treatment. In contrast, argatroban did not improve the outcome in MBL knockout mice.

Conclusions: MBL promotes brain damage and functional impairment after brain ischemia/reperfusion in mice. These effects are secondary to intravascular thrombosis and impaired relative cerebral blood flow during reperfusion. Argatroban protects WT mice, but not MBL knockout mice, emphasizing a role of MBL in local thrombus formation in acute ischemia/reperfusion.

Keywords: brain; complement pathway, mannose-binding lectin; complement system proteins; infarction, middle cerebral artery; reperfusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antithrombins / administration & dosage
  • Brain Ischemia / genetics
  • Brain Ischemia / metabolism
  • Brain Ischemia / physiopathology*
  • Cerebrovascular Circulation / genetics
  • Disease Models, Animal
  • Fibrinogen / antagonists & inhibitors
  • Fibrinogen / metabolism
  • Infarction, Middle Cerebral Artery / genetics
  • Infarction, Middle Cerebral Artery / metabolism
  • Infarction, Middle Cerebral Artery / physiopathology*
  • Magnetic Resonance Imaging
  • Male
  • Mannose-Binding Lectin / deficiency
  • Mannose-Binding Lectin / genetics
  • Mannose-Binding Lectin / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microcirculation / genetics
  • Pipecolic Acids / administration & dosage
  • Reperfusion Injury / genetics
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / physiopathology*
  • Thrombosis / etiology*
  • Thrombosis / genetics


  • Antithrombins
  • Mannose-Binding Lectin
  • Pipecolic Acids
  • Fibrinogen
  • argatroban