# Possible Impact of Lymphatic Drainage on Brain Injury After Aneurysmal Subarachnoid Hemorrhage

## TL;DR

This paper reviews how brain lymphatic drainage and cerebrospinal fluid circulation might influence brain injury after aneurysmal subarachnoid hemorrhage.

## Contribution

The paper provides a novel review connecting intracranial lymphatics and CSF dynamics to post-SAH brain injury mechanisms.

## Key findings

- Cerebral lymphatic vessels may play a role in free hemoglobin metabolism after SAH.
- Tenascin-C may inhibit lymphatic vessel proliferation, potentially worsening brain injury.
- Intracranial lymphatic function and CSF circulation are likely linked to early and delayed brain injury after SAH.

## Abstract

Subarachnoid hemorrhage (SAH) due to ruptured cerebral aneurysms is the most severe form of stroke, and treatment outcomes remain poor. Brain damage after SAH can be broadly divided into early brain injury (EBI) and delayed cerebral ischemia (DCI). Although the causes of these events are multifactorial, free hemoglobin generated after hemolysis in the subarachnoid space is believed to be one of the most important causative factors. Recently, cerebral lymphatic vessels, previously thought to be non-existent, have been identified, suggesting their involvement not only in maintaining homeostasis but also in brain injury. Furthermore, new findings have been reported regarding cerebrospinal fluid (CSF) circulation. Because intracranial CSF circulation and lymphatic drainage to the extracranial blood and lymphatic vessels affect free hemoglobin metabolism in the CSF, these factors are likely to affect EBI and DCI. In addition, matricellular protein tenascin-C, which we have reported to be involved in the pathogenesis of EBI and DCI, has been reported to inhibit lymphatic vessel proliferation in non-central nervous system pathologies. However, the relationship between post-SAH brain injury and intracranial lymphatics remains unknown. This review aimed to summarize recent findings regarding intracranial lymphatics and CSF circulation and to discuss how they may affect post-SAH pathology.