Browsing by Subject "meningeal lymphatic vessels"

Epileptic patients experience spontaneous recurrent seizures and interictal epileptiform discharges that lead to brain injuries, triggering neuroinflammation and waste product accumulation. Due to the detrimental effect of waste products on brain homeostasis, their removal from the central nervous system is (CNS) is crucial. Meningeal lymphatic vessels (mLVs) located in dura matter contribute to CNS clearance by the drainage of metabolites, waste products, and immune cells from subarachnoid space into cervical lymph nodes. Therefore, because of its role in brain homeostasis, the study of mLVs in different neurological conditions and diseases, including TLE, has gotten increased attention in the last decade. In this study, we sought to understand mLVs role in neuroinflammation and changes in rapid eye movement (REM) sleep stage during epilepsy. For this purpose, we induced mLVs ablation followed by kainic acid (KA) epilepsy model in mice. Shortly, animals were inoculated with AAV-VEGFR3-1-4 to induce mLVs ablation and subsequently challenged with KA to induce status epilepticus. Simultaneously, a control group of animals were injected with a sham AAV and later injection of KA. Afterward, spontaneous EEG activity was registered continuously, and data analysed to compare durations of REM sleep. Also, immunohistochemistry of brain samples was performed to investigate neuroinflammatory changes between experimental groups. Ex-vivo analyses of Iba1 and GFAP expression in brain tissue did not show statistically significant changes in neuroinflammation between experimental groups. However, we observed a trend towards lower expression of inflammatory markers in mLVs ablated animals. The analysis of REM sleep duration shows a progressive reduction of this sleep stage in both groups during the first recording period with a subsequent stabilization during the second one. Our data also indicate that mLVs ablated animals present prolonged REM sleep duration compared to the control group. Although this data contradicts our initial hypothesis it is consistent with the well-established negative correlation between neuroinflammation and REM sleep duration. Future studies should consider a deeper analysis of the glial cell profile for a better understanding of the effect of mLVs dysfunction on epileptic pathology. Moreover, the impact of mLVs ablation on REM sleep duration should be characterized in healthy animals.