gms | German Medical Science

Objective: Traumatic brain injury (TBI) is characterized by mechanical disruption of brain tissue due to an external force and by subsequent secondary injury. Secondary brain injury events include inflammatory responses and the activation of coagulation resulting in microthrombi formation in the brain vasculature. Recent research suggests that these mechanisms do not work independently. There is strong evidence that platelet activation connects both, inflammation and the formation of microthrombi. We therefore investigated the pathophysiological role of glycoprotein Ib (GPIb) and its inhibition in a mouse model of focal brain trauma.

Methods: Male, 12-week old C57Bl/6 mice were subjected to experimental focal TBI using a cortical cryogenic lesion model. 1 hour after injury induction, a GPIb antigen-binding fragment (α-GPIb) or vehicle solution were administered. Plasma concentrations of bradykinin were measured by ELISA immediately after trauma induction. Lesion size was determined by volumetry from brain slices stained with 2,3,5-triphenyltetrazolium chloride. To assess blood-brain-barrier damage and edema formation, intracerebral Evans Blue extravasation was measured by photometry. The amount of neuronal cell death and infiltrating immune cells was quantified in immunohistochemical stainings.

Results: Two hours after trauma, bradykinin plasma levels were increased in vehicle-treated mice in comparison to sham mice, whereas bradykinin remained at slightly lower levels in α-GPIb-treated animals. One day after trauma induction, a significant reduction in lesion size could be observed in α-GPIb-treated mice when compared with controls. A reduction of local inflammatory processes could be identified as underlying mechanism, which is not dependent on a preserved integrity of the blood-brain-barrier.

Conclusion: We here show that GPIb mediates tissue damage after TBI by enhancing inflammatory processes. This implies that platelet surface proteins like GPIb are not only essential in platelet activation and blood coagulation, but that they are also involved in mediating inflammatory processes. Therefore, there is a need for novel treatment strategies, which target inflammation and thrombosis synergistically following TBI.