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.

Shunt-dependent hydrocephalus (SDHC) is a delayed complication of aneurysmal subarachnoid hemorrhage (SAH), and meningeal fibrotic remodeling may contribute to its development. Secreted protein acidic and rich in cysteine (SPARC) regulates collagen processing and extracellular matrix organization. We examined whether serial plasma SPARC concentrations were associated with subsequent SDHC development. We retrospectively analyzed prospectively collected data from 186 patients with aneurysmal SAH enrolled in a multicenter registry. Plasma SPARC was measured at days 1–3, 4–6, 7–9, and 10–12 and analyzed using log-scale linear mixed-effects models. SDHC developed in 54 patients (29.0%). Model-estimated SPARC concentrations increased across periods in both SDHC and no-SDHC groups without a significant SDHC-by-period interaction, whereas all the SDHC/no-SDHC geometric mean ratios were below 1. The clearest difference occurred at days 4–6 and remained significant after adjustment for age, admission World Federation of Neurological Surgeons grade V, modified Fisher grade 4, and acute hydrocephalus (geometric mean ratio, 0.73; 95% confidence interval, 0.57–0.93; Holm-adjusted p = 0.040). In a post hoc exploratory multivariable analysis, each 10 ng/mL increase in SPARC at days 4–6 was associated with lower odds of subsequent SDHC development (adjusted odds ratio, 0.91; 95% confidence interval, 0.84–0.98; p = 0.011). Lower plasma SPARC concentrations, particularly at days 4–6, were associated with subsequent SDHC development.