The sentinel against brain injury post-subarachnoid hemorrhage: efferocytosis of erythrocytes by leptomeningeal lymphatic endothelial cells

Theranostics, Год журнала: 2025, Номер 15(6), С. 2487 - 2509

Опубликована: Янв. 20, 2025

Rationale: The clearance of extravasated erythrocytes represents the most reasonable strategy against brain injury post-subarachnoid hemorrhage (SAH). There is little knowledge about autologous post-SAH. leptomeningeal lymphatic endothelial cells (LLECs) have been less studied functionally, which were firstly harvested and cultured in vitro by our group previously are probably related to post-SAH for they closely surround subarachnoid space. Methods: We established a SAH animal model, employed primary LLECs vitro, mimicked conditions performed RNA sequencing, transfected with adenovirus adeno-associated virus both vivo reveal molecular mechanisms efferocytosis its neuroprotection Results: Firstly, we demonstrated eryptosis-initiated degradation vitro. Furthermore, found preferentially adhered engulfed apoptotic while sparing from intact erythrocytes, suggesting their novel capacity erythrocytes. Additionally, plays role on via improving neurological functions, maintaining neurostructural integrity, alleviating neuropathological consequences During efferocytosis, phosphatidylserine (PS) receptor (PSR) mediated recognition LLECs. also confirmed that NHL repeat-containing 2 (NHLRC2) positively regulated serve as central regulator it Conclusions: This study elucidated subsequently These findings highlight prompt, efficient, regulable pathway performs sentinel

Язык: Английский

Enhancing Th17 cells drainage through meningeal lymphatic vessels alleviate neuroinflammation after subarachnoid hemorrhage

Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)

Опубликована: Окт. 20, 2024

Язык: Английский

Enhancing Th17 cells drainage through meningeal lymphatic vessels alleviate neuroinflammation after subarachnoid hemorrhage

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Окт. 16, 2024

Background Subarachnoid hemorrhage (SAH) is a severe cerebrovascular disorder primarily caused by the rupture of aneurysm, which results in high mortality rate and consequently imposes significant burden on society. The occurrence SAH initiates an immune response that further exacerbates brain damage. acute inflammatory reaction subsequent to plays crucial role determining prognosis. Th17 cells, subset T are related injury following SAH, it unclear how cells cleared brain. Meningeal lymphatic vessels newly discovered intracranial fluid transport system has been shown drain large molecules deep cervical lymph nodes. There limited understanding meningeal SAH. objective this research explore impact underlying mechanism drainage Methods Treatments manipulate function CCR7-CCL21 pathway were administered, including laser ablation, injection VEGF-C, gene knockout protein injection. Mouse behavior was assessed using balance beam experiment modified Garcia scoring system. Flow cytometry, enzyme-linked immunosorbent assays (ELISA), immunofluorescence staining used study drainage. Select patients with unruptured ruptured aneurysms our hospital as control group group, 7 cases each group. Peripheral blood cerebrospinal (CSF) samples ELISA flow cytometry. Results Mice showed substantial behavioral abnormalities damage accumulated Laser ablation or CCR7 leads aggregation meninges, resulting decreased neurological score increased levels factors. Injection VEGF-C CCL21 promotes nodes, score, Clinical CSF factors significantly increased. number higher than confirmed aggravated level neuroinflammation after Conclusion This shows improving lymphatics via can reduce improve mouse model. could lead new treatment options for

Язык: Английский