Mechanisms of edema formation after intracerebral hemorrhage: effects of thrombin on cerebral blood flow, blood-brain barrier permeability, and cell survival in a rat model

TLDR

Thrombin contributes to brain edema after intracerebral hemorrhage. The study investigates whether thrombin’s effects on cerebral blood flow, vasoreactivity, BBB function, or cell viability underlie edema formation. Thrombin was stereotactically infused into rat basal ganglia, and after 24 h CBF and BBB permeability were measured, vasoreactivity was assessed in cortical slices, and C6 glioma cells were exposed to thrombin to quantify cell death via LDH release. Thrombin causes BBB disruption and parenchymal cell death but does not alter CBF or vasoreactivity, indicating that cell toxicity and BBB breakdown trigger edema after intracerebral hemorrhage.

Abstract

Recently, the authors showed that thrombin contributes to the formation of brain edema following intracerebral hemorrhage. The current study examines whether the action of thrombin is due to an effect on cerebral blood flow (CBF), vasoreactivity, blood-brain barrier (BBB) function, or cell viability. In vivo solutions of thrombin were infused stereotactically into the right basal ganglia of rats. The animals were sacrificed 24 hours later; CBF and BBB permeability were measured. The actions of thrombin on vasoreactivity were examined in vitro by superfusing thrombin on cortical brain slices while monitoring microvessel diameter with videomicroscopy. In separate experiments C6 glioma cells were exposed to various concentrations of thrombin, and lactate dehydrogenase release, a marker of cell death, was measured. The results indicate that thrombin induces BBB disruption as well as death of parenchymal cells, whereas CBF and vasoreactivity are not altered. The authors conclude that cell toxicity and BBB disruption by thrombin are triggering mechanisms for the edema formation that follows intracerebral hemorrhage.