Functional Investigation of Meningeal Lymphatic System in Experimental Intracerebral Hemorrhage

Tsai, Hsin‐Hsi; Hsieh, Yung-Chia; Lin, Jhih Syuan; Kuo, Zi-Ting; Ho, Chi-Ying; Chen, Chih-Hung; Chang, C.

doi:10.1161/strokeaha.121.037834

Cited by 35 publications

(48 citation statements)

References 50 publications

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“…By bridging the CNS with the peripheral immune system, MLVs control both brain waste clearance and neuroimmune communication. MLV dysfunction affects various mouse models of neurological disorders, including multiple sclerosis (MS), Alzheimer’s disease, ischemic stroke, intracerebral hemorrhage, traumatic brain injury, and brain tumors ( Louveau et al, 2016 , 2018 ; Da Mesquita et al, 2018 ; Hsu et al, 2019 ; Esposito et al, 2019 ; Song et al, 2020 ; Hu et al, 2020 ; Bolte et al, 2020 ; Da Mesquita et al, 2021 ; Tsai et al, 2022 ). MLVs have thus become attractive as potential therapeutic targets against CNS pathologies.…”

Section: Introductionmentioning

confidence: 99%

Conserved meningeal lymphatic drainage circuits in mice and humans

Jacob

Neto

Lenck

et al. 2022

Journal of Experimental Medicine

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Meningeal lymphatic vessels (MLVs) were identified in the dorsal and caudobasal regions of the dura mater, where they ensure waste product elimination and immune surveillance of brain tissues. Whether MLVs exist in the anterior part of the murine and human skull and how they connect with the glymphatic system and extracranial lymphatics remained unclear. Here, we used light-sheet fluorescence microscopy (LSFM) imaging of mouse whole-head preparations after OVA-A555 tracer injection into the cerebrospinal fluid (CSF) and performed real-time vessel-wall (VW) magnetic resonance imaging (VW-MRI) after systemic injection of gadobutrol in patients with neurological pathologies. We observed a conserved three-dimensional anatomy of MLVs in mice and humans that aligned with dural venous sinuses but not with nasal CSF outflow, and we discovered an extended anterior MLV network around the cavernous sinus, with exit routes through the foramina of emissary veins. VW-MRI may provide a diagnostic tool for patients with CSF drainage defects and neurological diseases.

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Section: Introductionmentioning

confidence: 99%

Conserved meningeal lymphatic drainage circuits in mice and humans

Jacob

Neto

Lenck

et al. 2022

Journal of Experimental Medicine

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“…Although almost no studies have explored the relationship between the cerebral drainage venous system and PHE in animals, there have been studies on the influence of the cerebral drainage venous system on PHE in patients with ICH [ 125 – 127 ]. Blocking of brain lymphatic drainage can exacerbate brain edema, neuroinflammation, and neuronal death and cause neurologic deficits in animals with acute ICH [ 128 , 129 ]. Furthermore, the brain lymphatic drainage system is also involved in clearing brain waste from blood after ICH in animals [ 130 ].…”

Section: Factors That May Impact Phementioning

confidence: 99%

“…Regarding ICH, although previous studies have illustrated that abnormalities in the brain lymphatic drainage system can promote the formation of brain edema in animals [ 128 , 129 ], no research has provided information on changes in the brain lymphatic drainage system and its relationship with PHE in patients with ICH [ 161 – 164 ]. Relevant future studies will provide information on the mechanism of post-ICH PHE formation.…”

Section: Factors That May Impact Phementioning

confidence: 99%

Molecular, Pathological, Clinical, and Therapeutic Aspects of Perihematomal Edema in Different Stages of Intracerebral Hemorrhage

Jiang

Guo

Zhang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Acute intracerebral hemorrhage (ICH) is a devastating type of stroke worldwide. Neuronal destruction involved in the brain damage process caused by ICH includes a primary injury formed by the mass effect of the hematoma and a secondary injury induced by the degradation products of a blood clot. Additionally, factors in the coagulation cascade and complement activation process also contribute to secondary brain injury by promoting the disruption of the blood-brain barrier and neuronal cell degeneration by enhancing the inflammatory response, oxidative stress, etc. Although treatment options for direct damage are limited, various strategies have been proposed to treat secondary injury post-ICH. Perihematomal edema (PHE) is a potential surrogate marker for secondary injury and may contribute to poor outcomes after ICH. Therefore, it is essential to investigate the underlying pathological mechanism, evolution, and potential therapeutic strategies to treat PHE. Here, we review the pathophysiology and imaging characteristics of PHE at different stages after acute ICH. As illustrated in preclinical and clinical studies, we discussed the merits and limitations of varying PHE quantification protocols, including absolute PHE volume, relative PHE volume, and extension distance calculated with images and other techniques. Importantly, this review summarizes the factors that affect PHE by focusing on traditional variables, the cerebral venous drainage system, and the brain lymphatic drainage system. Finally, to facilitate translational research, we analyze why the relationship between PHE and the functional outcome of ICH is currently controversial. We also emphasize promising therapeutic approaches that modulate multiple targets to alleviate PHE and promote neurologic recovery after acute ICH.

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“…Conversely, disrupting mLVs function either by visudyne depletion or by ligation of the dCLNs disrupted intra‐parenchymal hematoma resolution after ICH. On the contrary, improving mLVs function by intra‐cisterna magna (ICM) administration of VEGFc improved hematoma resolution after ICH 165 . Furthermore, Yanev et al, (2020) investigated the involvement of mLVs in two different mouse models of stroke, the transient middle cerebral artery occlusion (tMCAO) and photothrombosis.…”

Section: Meninges In Neurological Disordersmentioning

confidence: 99%

“…On the contrary, improving mLVs function by intra-cisterna magna (ICM) administration of VEGFc improved hematoma resolution after ICH. 165 Furthermore, Yanev et al, (2020) investigated the involvement of mLVs in two different mouse models of stroke, the transient middle cerebral artery occlusion (tMCAO) and photothrombosis.…”

Section: Brain Injurymentioning

confidence: 99%

Neuroimmune signaling at the brain borders

Frederick

Tavares

Louveau

2022

Immunological Reviews

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The central nervous system has traditionally been viewed as an immune privilege site with increased tolerance towards antigens that would induce rejection and limited immune responses against CNS antigens. 1 Sir Peter Medawar established this concept when performing his transplantation experiments demonstrating delayed rejection of skin graft in the brain. 2 He postulated that the immune privilege function of the brain arose primarily from (i) lack of drainage of CNS antigens to mount immune responses; (ii) isolation of the brain from peripheral infiltration through the blood brain barrier; and (iii) the relative absence of antigen presenting cells within the CNS. However, further studies demonstrated that rather than isolation and ignorance of the CNS by the immune system, it is rather tightly regulated interactions between immune cells and the CNS that control the apparent immune privilege status of the brain. 3,4 Likely, these controlled interactions are in place to limit neuronal damages while ensuring protection of the brain from infections and facilitate tissue repair.The anatomical sites where most of these interactions appear to take place are particularly located at the borders of the CNS. While the brain parenchyma is virtually devoid of immune cells, with exception of microglia and mast cells, its borders are populated with numerous innate and adaptive immune cells that actively communicate with the periphery to ensure surveillance and protection of the CNS.Yet we still know very little about the establishment, maintenance, and function of these brain borders. New technical advances and a deeper understanding of neuroimmune interactions are driving the field toward the definition of compartmentalized interactions between the brain and the immune system to allow for synergic control and maintenance of brain function in health and disease.Here, we will discuss the establishment and maintenance of the three primary brain borders, the meninges, the choroid plexus, and the blood brain barrier. We then dive into the described roles of the

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Functional Investigation of Meningeal Lymphatic System in Experimental Intracerebral Hemorrhage

Cited by 35 publications

References 50 publications

Conserved meningeal lymphatic drainage circuits in mice and humans

Conserved meningeal lymphatic drainage circuits in mice and humans

Molecular, Pathological, Clinical, and Therapeutic Aspects of Perihematomal Edema in Different Stages of Intracerebral Hemorrhage

Neuroimmune signaling at the brain borders

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