Introduction: Cerebral venous thrombosis (CVT) is a rare form of cerebral stroke that causes a wide range of presentations ranging from mild headache to severe morbidity or death in the severer forms. Treatment of CVT is classically in the form of anti-coagulation or thrombolysis, but there is a little focus on developing new therapies for its treatment. In this work we used a rat model of superior sagittal sinus thrombosis to induce CVT in order to study the pathophysiologic mechanisms that occur during CVT evolution.
Methods: CVT was induced in rats using Ferric-chloride applied to the superior sagittal sinus. Rats were followed from 6 hours to 14 days. Using qPCR, immunohistochemistry, western blotting and Gel zymogrpahy we evaluated immune cell activation, blood brain barrier breakdown and inflammasome activation. We followed the
Results: Our data shows intense activation of immune cells particularly microglia, with increase macrophage activity and NLRP3 inflammasome activation and pyroptotic cell death. Astrocytes were also activated and induced glial scar leading to parenchymal contraction in the subacute stage and tissue loss. MMP9 was identified as the main culprit in BBB breakdown after CVT and is mainly produced by pericytes.
Conclusions: Our data showed an inflammation driven pathophysiology of CVT that follows MMP9-mediated BBB breakdown, and identified several targets that can be used to modify neuroinflammation that follows CVT with potential to go into clinical practice.
Patient Care: In this work we explored in depth the pathology of CVT. While research have highlighted the etiology of CVT, not much have been done to explore the parenchymal changes that follow SSS thrombosis, and treatment is largely anti-coagulants or thrombolysis with no focus on targetting the pathological cascade that already started following SSS thrombosis. In this work we highlighted several mechanisms that occur during CVT evolution, pointing out to several drug-able targets that can be further explored to improve the treatment outcome in patients suffering from CVT
Learning Objectives: By the conclusion of this session, participants should be able to:1) understand in depth the pathophysiological mechanisms that governs CVT evolution. 2) appreciate the role of inflammation in the pathology of CVT. 3) Identify several targets that can be used for treating CVT, some of which are already in clinical practice.