Abstract 100: Meningeal Lymphatic System Modulates Intra-parenchymal Hematoma Clearance And Brain Recovery In Experimental Intracerebral Hemorrhage

Abstract

Background: Intracerebral hemorrhage (ICH) brain injury is induced by toxic blood components and subsequent neurologic deficits can be alleviated by promoting hematoma resolution. The meningeal lymphatic system has been shown to mediate substances clearance from the central nervous system, including macromolecules and pathogenic metabolites. However, it remains unclear whether this system plays a role in hematoma clearance and ICH outcomes. In this study, we investigated the correlation between meningeal lymphatic function and ICH pathologies. Pharmacological promotion of meningeal lymphatic function was also used to determine whether targeting meningeal lymphatic system can facilitate ICH recovery. Methods: Whole-mount meninges were used to evaluate the complexity and coverage rate of meningeal lymphatic vessels. Meningeal lymphatic drainage was evaluated by injecting fluorescent microbeads and PKH26-labeled erythrocytes into the cisterna magna and brain parenchyma, respectively. Hematoma volume was measured in fresh coronal brain sections. Neurobehavioral performance was evaluated by cylinder test. Pathological outcomes including iron deposition, residual erythrocytes, neuronal loss, and astrogliosis were detected by immunohistochemistry or immunofluorescence. Results: Meningeal lymphangiogenesis and increased lymphatic drainage occur during the late phase of ICH. Depriving the function of meningeal lymphatic vessels impeded hematoma clearance, whereas boosting meningeal lymphatic drainage and lymphangiogenesis improved hematoma clearance rate and behavioral function as well as reduced iron deposition, neuronal loss, and astrogliosis in the ICH brain. Conclusion: Early enhancement of meningeal lymphatic function is beneficial for ICH recovery, implicating the meningeal lymphatic system as a potential therapeutic target for treating ICH.