Advertisement

Lactadherin Promotes Microvesicle Clearance to Prevent Coagulopathy and Improves Survival of Severe TBI Mice

Yuan Zhou, Wei Cai, Zilong Zhao, Tristan Hilton, Min Wang, Jason Yeon, Wei Liu, Fangyi Zhang, Fu-Dong Shi, Xiaoping Wu, Perumal Thiagarajan, Min Li, Jianning Zhang and Jing-fei Dong

Key points

  • Lactadherin promotes the clearance of circulating microvesicles through phagocytosis.

  • Promoting microvesicle clearance prevents coagulopathy, reduces cerebral edema, and improves neurological function in severe TBI mice.

Abstract

Coagulopathy is common in patients with traumatic brain injury (TBI) and predicts poor clinical outcomes. We have shown that brain-derived extracellular microvesicles, including extracellular mitochondria, play a key role in the development of TBI-induced coagulopathy. Here, we further show in mouse models that the apoptotic cell-scavenging factor lactadherin, given at a single dose of 400 µg/kg 30 min before (preconditioning) or 30 min after cerebral fluid percussion injury, prevented coagulopathy as defined by clotting time, fibrinolysis, intravascular fibrin deposition, and microvascular bleeding of the lungs. Lactadherin also reduced cerebral edema, improved neurological function, and increased survival. It achieved these protective effects by enhancing the clearance of circulating microvesicles through phosphatidylserine-mediated phagocytosis. Together, these results identify the scavenging system for apoptotic cells as a potential therapeutic target to prevent TBI-induced coagulopathy and improve the outcome of TBI.

  • Submitted August 15, 2017.
  • Accepted November 5, 2017.