Meningeal lymphatics can influence stroke outcome

Abstract

Meningeal lymphatics are conduits for cerebrospinal fluid drainage to lymphatics and lymph nodes in the neck. In this issue of JEM, Boisserand et al. (https://doi.org/10.1084/jem.20221983) provide evidence that expansion of meningeal lymphatics protects against ischemic stroke.

Insights from Gou Young Koh and Donald M. McDonald.

Meningeal lymphatics can influence stroke outcome. The beneficial contributions of meningeal lymphatics to the outcome of stroke and TBI are illustrated. (A) AAV delivery of VEGF-C to the CSF expands the meningeal lymphatic network and increases CSF drainage to cervical lymph nodes of adult mice and improves neurologic function after ischemic stroke resulting from transient occlusion of the middle cerebral artery (Boisserand et al., 2024). As an infusion of VEGF-C protein is ineffective after ischemia, the approach is not useful after stroke treatment (Boisserand et al., 2024). (B) Another recent study (Hussain et al., 2023) reports that cerebral edema occurring in a head concussion model of TBI results from suppression of CSF outflow caused by excessive systemic release of noradrenaline. This adrenergic storm reduces the contractility of cervical lymphatics, which in turn reduces CSF outflow and promotes cerebral edema. In support of this mechanism, the study (Hussain et al., 2023) reports that pan-adrenergic receptor blockade increases contractility of cervical lymphatics, restores CSF outflow, and reduces cerebral edema in mice with TBI. However, the characterization of CSF drainage through superficial and deep cervical lymphatics and lymph nodes and the feasibility of safely treating TBI patients with pan-adrenergic antagonists deserve further consideration.