Impaired meningeal lymphatic vessels exacerbate early brain injury after experimental subarachnoid hemorrhage

Liu, Quanlei; Hou, Changkai; Zhang, Hao; Fu, Cong; Wang, Weihan; Wang, Bangyue; Li, Jian; Zhao, Yan; Yang, Xinyu

doi:10.1016/j.brainres.2021.147584

Cited by 10 publications

(8 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cerebral cortical perfusion of the whole convexity was measured using a laser speckle blood monitor (PeriCam PSI System, Sweden) at 6 h after SAH as previously described [ 37 , 38 ]. The mice were mounted on a stereotaxic frame, and a midline incision was made to expose the calvaria.…”

Section: Methodsmentioning

confidence: 99%

The Role of Neutrophil Extracellular Traps in Early Microthrombosis and Brain Injury After Subarachnoid Hemorrhage in Mice

Hao

Zeng

Liang

et al. 2022

Transl. Stroke Res.

View full text Add to dashboard Cite

Microthrombosis plays an important role in secondary brain injury after experimental subarachnoid hemorrhage (SAH), but the specific mechanism of microthrombosis remains unclear. The purpose of this study was to investigate the role of neutrophil extracellular traps (NETs) in microthrombosis after SAH. SAH was induced in male C57BL/6 mice using an endovascular perforation technique. The marker protein of NETs, citrullinated histone H3 (CitH3), was significantly elevated in the cerebral cortex after SAH, and was co-labeled with microthrombi. Both depletion of neutrophils by anti-Ly6G antibody and DNase I treatment significantly reduced the formation of NETs and microthrombi, and ameliorated neurological deficits, brain edema, BBB disruption, and neuronal injury at 24 h after SAH induction. Cerebral hypoperfusion in the first hours after SAH is a major determinant of poor neurological outcome; in this study, we found that DNase I treatment significantly improved the restoration of early cortical perfusion after SAH. In addition, DNase I treatment also significantly attenuated cerebrospinal fluid (CSF) flow after SAH, which was associated with the diffusion barrier caused by microthrombi in the paravascular space after SAH. In conclusion, NETs are associated with early microthrombosis after SAH; they may be a novel therapeutic target for early brain injury (EBI) after SAH. Supplementary Information The online version contains supplementary material available at 10.1007/s12975-022-01074-9.

show abstract

Section: Methodsmentioning

confidence: 99%

The Role of Neutrophil Extracellular Traps in Early Microthrombosis and Brain Injury After Subarachnoid Hemorrhage in Mice

Hao

Zeng

Liang

et al. 2022

Transl. Stroke Res.

View full text Add to dashboard Cite

show abstract

“…Currently, the developments of microscopic technology, drug support, and medical experience in departments of neurosurgery have played a positive role in the early diagnosis, early treatment, and post-operative care of SAH, but the serious social problems brought by SAH cannot be ignored (20). Studies have shown that the complex physiopathological mechanisms following EBI are essential for the development of prognosis in the course after SAH, rendering the systematic study of the early stage of SAH very necessary (21)(22)(23).…”

Section: Discussionmentioning

confidence: 99%

Dynamic Evolution of the Glymphatic System at the Early Stages of Subarachnoid Hemorrhage

Hou

Wang

et al. 2022

Front. Neurol.

Self Cite

View full text Add to dashboard Cite

The early stages of subarachnoid hemorrhage (SAH) are extremely important for the progression and prognosis of this disease. The glymphatic system (GS) has positive implications for the nervous system due to its ability to clearance tau and amyloid-β (Aβ) protein. Previous studies have shown that GS dysfunction will appear after SAH. However, there is no systematic evaluation of the degree of damage and development process of GS function in the early stage after SAH. In this study, we evaluated the GS function and neurobehavioral in the sham, 6 h, 1, 3, and 7 days after SAH, respectively. Our results showed that the function of GS was severely attenuated in mice after SAH with a decreased polarity of Aquaporin-4 (AQP4), increased expression of AQP4, a linear correlation with the dystrophin-associated complex (DAC), the proliferation of reactive astrocytes, increased tau protein accumulation, and decreased neurological function. Collectively, these findings provide a comprehensive understanding of the functional changes of GS after SAH, provide references for subsequent scholars studying SAH, and suggest some potential mechanistic insight that affects AQP4 polarity and GS function.

show abstract

“…While mice subjected to SAH display improved brain perfusion 24 h after the lesion, mice subjected to mLVs ablation show slightly improvements only or even worsening of brain perfusion. Notably, the ablation of the mLVs was associated with aggravated neurological deficits and worse brain edema in mice subjected to SAH, in addition to increased neuroinflammation and neural apoptosis 169 . Furthermore, in mice with underdeveloped mLVs (K14‐VEGFR3‐Ig), it is observed decreased CD4+ T‐cell infiltration within the brain parenchyma one month after controlled cortical impact, as a model of TBI.…”

Section: Meninges In Neurological Disordersmentioning

confidence: 97%

“…Notably, the ablation of the mLVs was associated with aggravated neurological deficits and worse brain edema in mice subjected to SAH, in addition to increased neuroinflammation and neural apoptosis. 169 Furthermore, in mice with underdeveloped mLVs (K14-VEGFR3-Ig), it is observed decreased CD4+ T-cell infiltration within the brain parenchyma one month after controlled cortical impact, as a model of TBI. This suggests that mLVs are required for proper immune response to brain traumatic injury.…”

Section: Brain Injurymentioning

confidence: 99%

Neuroimmune signaling at the brain borders

Frederick

Tavares

Louveau

2022

Immunological Reviews

View full text Add to dashboard Cite

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

show abstract

Impaired meningeal lymphatic vessels exacerbate early brain injury after experimental subarachnoid hemorrhage

Cited by 10 publications

References 19 publications

The Role of Neutrophil Extracellular Traps in Early Microthrombosis and Brain Injury After Subarachnoid Hemorrhage in Mice

The Role of Neutrophil Extracellular Traps in Early Microthrombosis and Brain Injury After Subarachnoid Hemorrhage in Mice

Dynamic Evolution of the Glymphatic System at the Early Stages of Subarachnoid Hemorrhage

Neuroimmune signaling at the brain borders

Contact Info

Product

Resources

About