1205. Role of the Meninges and Meningeal Lymphatic System in the Immune Response after Ischemic Stroke

Authors: Jennifer D. Sokolowski, MD; Petr Tvrdik, PhD; Yashar Kalani, MD, PhD (Charlottesville, VA)

Introduction: Acute cerebral ischemia leads to an inflammatory reaction that may exacerbate secondary injury; evidence suggests that modulation of the immune response holds promise as an adjunct treatment for stroke. Ischemia triggers well-described infiltration of immune cells into the infarct zone in the parenchyma, but no work has been done to examine the response in the meninges and there have been no attempts to target trafficking of fluid, debris, or immune cells in the meninges for treatment of stroke. The recent identification of dural lymphatics has reignited interest in looking at mechanisms of immune infiltration and clearance in the setting of disease. Studies have just begun to characterize the human dural lymphatics, and they have not been well-described. Methods: In this study we collected dura from postmortem patients and surgical samples from patients with benign brain tumors or post-ischemic stroke (hemicraniectomy). We are creating an atlas of dural lymphatics in man using a combination of immunohistochemistry and RNA profiling and examining immune changes that occur in the dura after stroke. Results: We identify an increase in infiltration of immune cells, especially Lyve-1-positive macrophages in the dura after stroke. Our data suggests that meningeal lymphatics play a role in the immune response after ischemic stroke. Conclusion: The meninges may perpetuate a detrimental inflammatory reaction; further work is being done in animal models to evaluate this.Manipulating transport of immune cells and inflammatory signals through meningeal lymphatics may enable us to modulate the immune response and minimize secondary injury after acute ischemic stroke. Importantly, this may be an innovative approach to manipulate the immune system in a host of neurological diseases.