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0 reviewsCross-talk between the brain and cervical lymph nodes (CLNs) is crucial in brainpathologies. However, the precise roles and the mechanisms of CLNs in braindamage during subarachnoid hemorrhage (SAH) remain unclear. In this study,mandibular lymph node (part of CLNs) removal attenuates brain damage inSAH mouse models. Notably, the extravasated erythrocytes following SAH aresignificantly engulfed by lymphatic endothelial cells (LECs) in CLNs. Single-cellRNA sequencing reveals that the differentially expressed genes in medullaryLECs are enriched in lysosomes after SAH, with a notable upregulation of Ctss(which encodes cathepsin S). Importantly, the deficiency of cathepsin S specifically in LECs, achieved through transgenic mice, or the use of a cathepsinS inhibitor, significantly reduces neuroinflammation and neurological deficitsinduced by SAH. These findings elucidate mechanisms of how CLNs participatein brain injury following SAH in mice. Targeting this process may offer effectivetherapeutic strategies to alleviate SAH-related pathologies.
