Meningeal lymphatics clear erythrocytes that arise from subarachnoid hemorrhage

Abstract

Extravasated erythrocytes in cerebrospinal fluid (CSF) critically contribute to the pathogenesis of subarachnoid hemorrhage (SAH). Meningeal lymphatics have been reported to drain macromolecules and immune cells from CSF into cervical lymph nodes (CLNs). However, whether meningeal lymphatics are involved in clearing extravasated erythrocytes in CSF after SAH remains unclear. Here we show that a markedly higher number of erythrocytes are accumulated in the lymphatics of CLNs and meningeal lymphatics after SAH. When the meningeal lymphatics are depleted in a mouse model of SAH, the degree of erythrocyte aggregation in CLNs is significantly lower, while the associated neuroinflammation and the neurologic deficits are dramatically exacerbated. In addition, during SAH lymph flow is increased but without significant lymphangiogenesis and lymphangiectasia. Taken together, this work demonstrates that the meningeal lymphatics drain extravasated erythrocytes from CSF into CLNs after SAH, while suggesting that modulating this draining may offer therapeutic approaches to alleviate SAH severity.

Photostimulation of lymphatic clearance of red blood cells from the mouse brain after intraventricular hemorrhage

“…These results provide strong support for the old theory of RBCs evacuation from the brain via lymphatic efflux [12][13][14][15][16][17]. Our data are also consistent with the newest discovery of the meningeal lymphatic pathway of clearance of RCBs from the brain after brain hemorrhage [25,26]. Taking into account all of the above, we hypothesized that the lymphatic mechanisms of blood clearance from the brain can be a new therapeutic target for treatment of IVH.…”

“…Quite recently the old concept of lymphatic pathway of RBC move from the brain was supplemented by new knowledge of RBCs clearance via the meningeal lymphatic vessels (MLVs) after ICH that was first proposed by our group in 2019 [25] and afterward it was studied after SAH by Chinese group in 2020 [26]. However, it still remain unanswered, whether RBCs can move from the ventricles into the lymphatic system and if so, whether this process can be therapeutically stimulated.…”

The Glymphatic System: A Review of the Challenges in Visualizing its Structure and Function with MR Imaging

“…Modulation of this drainage may offer therapeutic approaches to alleviate subarachnoid hemorrhage severity. 95 It is also shown that subdural hematoma was absorbed through the meningeal lymphatic vessel drainage pathway and that hematomas could inhibit the function of meningeal lymphatic vessels. 96 In the search for the T-cell gateways into and out of the meninges, functional lymphatic vessels lining the dural sinuses were discovered.…”

A Destruction Model of the Vascular and Lymphatic Systems in the Emergence of Psychiatric Symptoms

“…The midbrain close to the periaqueductal gray is implicated in the expression of autonomic nervous system activity via serotonergic neurons, which regulate the sleep/wake rhythm as well as mode and cognition. The cerebellum is one of the hottest regions newly known related to distinct psychiatric disorders: autism spectrum disorders (ASDs), schizophrenia, and mood disorders [ 10 , 29 , 30 , 31 ], although the cerebellum had been considered the central area of motor coordination, and cerebellar abnormalities were believed to exclusively induce coordination disorder and tremor [ 32 , 33 , 34 ]. Therefore, the view of aberrant immune-triggered psychiatric disorders should be noticed what brain regions are functionally disrupted and what connections of brain regions are impaired.…”

“…In the disease model, monocytic infiltration is observed with progression to paralytic stages of EAE [ 115 ]. Parenchymal microglia modulate the intrinsic excitability [ 10 , 29 , 118 ] and the efficacy of synaptic transmission [ 119 ] of CNS neurons. They also engulf dendritic spines via C1q complement signaling in the developmental and senile brain [ 120 , 121 ].…”