Yuanjian Fang

Meningeal lymphatic vessels (mLVs) play a critical role in clearing erythrocytes from the subarachnoid space and immune cells from the brain parenchyma following subarachnoid hemorrhage (SAH). However, the drainage function of mLVs is impaired during the acute stage after SAH and gradually recovers in the subacute phase. We aimed to investigate the meningeal transcriptional response post-SAH and elucidate the dynamic influence of meningeal microenvironment on meningeal lymphatic function. We employed bioinformatics analysis of single-cell RNA sequencing and spatial transcriptomics to characterize the spatiotemporal dynamic changes in the early meningeal microenvironment post-SAH. In a mouse model of SAH, the early dynamic changes of the meningeal immune cells and the potential growth factor that promoted the early repair of the mLVs were further investigated and validated. During the acute phase, myeloid cells early infiltrated the meninges and triggered inflammatory responses. In the subacute phase, the fibroblast population expanded significantly, contributing to tissue remodeling. The interplay between immune cells and fibroblasts regulated cell migration and phenotypic transition, potentially affecting the function of mLVs. Notably, placental growth factor (PGF) emerged as the most prominent ligand within the VEGF signaling pathway received by meningeal lymphatic endothelial cells (mLECs) post-SAH. This signaling event was associated with the early recovery of mLVs after acute immune responses. Our study revealed a spatiotemporal transformation of the meningeal microenvironment from an “inflammatory response” phase to a “tissue remodeling” phase following SAH. Monocyte-derived macrophages and self-recruiting neutrophils contributed to impairment of mLVs in the acute stage, while PGF might serve as a key factor promoting early meningeal lymphatic function repair following the inflammatory response. These findings provided novel insights into the cellular dynamics underlying mLVs dysfunction and recovery post-SAH.

This study aimed to analyze the existing evidence on the association between dental diseases and stroke. Various pathogenic mechanisms, including bacteraemia and systemic inflammation, were investigated to explore their impact on stroke occurrence and severity. A comprehensive literature search was conducted through the online databases PubMed, Google Scholar, Web of Science, and Scopus. The initial screening process resulted in a total of 138 articles being gathered. Upon subsequent refinement, 52 articles were discarded due to duplication or non-English language, leaving 86 articles for further assessment. Oral bacteria can travel to the brain’s blood vessels and cause bacteraemia, leading to local inflammation and the release of toxins. This process can result in the blockage or rupture of blood vessels, leading to stroke. Oral infections consistently trigger immune responses and systemic inflammation, with inflammation-related proteins playing a crucial role in stroke development. Notably, periodontal treatment could reduce the risk of stroke. This review emphasizes the role of dental diseases in promoting stroke occurrence through various mechanisms. Dental diseases contribute to the development of stroke by facilitating bacteraemia and systemic inflammation. Furthermore, through effectively treating and preventing dental diseases, the risk of strokes can be significantly reduced.

Background: Subarachnoid hemorrhage (SAH) represents a severe stroke subtype. Our study aims to develop gender‐specific prognostic prediction models derived from distinct prognostic factors observed among different‐gender patients.Methods: Inclusion comprised SAH‐diagnosed patients from January 2014 to March 2016 in our institution. Collected data encompassed patients' demographics, admission severity, treatments, imaging findings, and complications. Three‐month post‐discharge prognoses were obtained via follow‐ups. Analyses assessed gender‐based differences in patient information. Key factors underwent subgroup analysis, followed by univariate and multivariate analyses to identify gender‐specific prognostic factors and establish/validate gender‐specific prognostic models.Results: A total of 929 patients, with a median age of 57 (16) years, were analyzed; 372 (40%) were male, and 557 (60%) were female. Differences in age, smoking history, hypertension, aneurysm presence, and treatment interventions existed between genders (p < 0.01), yet no disparity in prognosis was noted. Subgroup analysis explored hypertension history, aneurysm presence, and treatment impact, revealing gender‐specific variations in these factors' influence on the disease. Screening identified independent prognostic factors: age, SEBES score, admission GCS score, and complications for males; and age, admission GCS score, intraventricular hemorrhage, treatment interventions, symptomatic vasospasm, hydrocephalus, delayed cerebral ischemia, and seizures for females. Evaluation and validation of gender‐specific models yielded an AUC of 0.916 (95% CI: 0.878–0.954) for males and 0.914 (95% CI: 0.885–0.944) for females in the ROC curve. Gender‐specific prognostic models didn't significantly differ from the overall population‐based model (model 3) but exhibited robust discriminative ability and clinical utility.Conclusion: Variations in baseline and treatment‐related factors among genders contribute partly to gender‐based prognosis differences. Independent prognostic factors vary by gender. Gender‐specific prognostic models exhibit favorable prognostic performance.

Editorial: Crosstalk between peripheral and local immune response in the pathophysiology of stroke and neurodegeneration diseases, volume II

Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage. The E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and maturation. However, the effect of Spi1 on intracerebral hemorrhage remains unclear. In this study, we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage transcriptome. We showed that high Spi1 expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis, glycolysis, and autophagy, as well as debris clearance and sustained remyelination. Notably, microglia with higher levels of Spi1 expression were characterized by activation of pathways associated with a variety of hemorrhage-related cellular processes, such as complement activation, angiogenesis, and coagulation. In conclusion, our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral hemorrhage. This new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.

Meningeal lymphatic vessels (mLVs) were recently discovered to be involved in the waste drainage process in the brain, which has also been associated with a variety of neurological diseases. This research paper hypothesizes that the drainage function of mLVs may be affected after chronic subdural hematoma (CSDH) and the alterations of mLVs’ drainage may predict CSDH recurrence. In this prospective observational study, unenhanced 3D T2-fluid-attenuated inversion recovery (3D T2-FLAIR) MRI data were collected from CSDH patients and healthy participants for analysis. Patients with CSDH who underwent surgery received MRI scans before and after surgery, whereas healthy controls and patients with CSDH who received pharmaceutical treatment received only one MRI scan at enrollment. The signal unit ratio (SUR) of mLVs were then measured according to the MRI data and calculated to define mLVs’ drainage function. Finally, the relationship between mLVs’ drainage function and CSDH recurrence was analyzed accordingly. Thirty-four participants were enrolled in this study, including 27 CSDH patients and 7 controls. The SUR of mLVs in all CSDH patients changed significantly before and after surgery. Moreover, the drainage function of the mLVs ipsilateral to hematoma (mLVs-IH) in CSDH patients was significantly lower than that in the controls (p < 0.05). Last, a higher improvement rate of the drainage function of the mLVs-IH is correlated to a lower risk of recurrence (p < 0.05). This study revealed the mLVs’ drainage dysfunction after CSDH through non-invasive MRI. Furthermore, the drainage function of mLVs is an independent predictive factor of CSDH recurrence.