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Background: Subarachnoid hemorrhage (SAH) is an uncommon type of potentially fatal stroke. The pathophysiological mechanisms of brain injury remain unclear, which hinders the development of drugs for SAH. We aimed to investigate the pathophysiological mechanisms of SAH and to elucidate the cellular and molecular biological response to SAH-induced injury., Methods: A cross-species (human and mouse) multiomics approach combining high-throughput data and bioinformatic analysis was used to explore the key pathophysiological processes and cells involved in SAH-induced brain injury. Patient data were collected from the hospital (n = 712). SAH was established in adult male mice via endovascular perforation, and flow cytometry, a bone marrow chimera model, qPCR, and microglial depletion experiments were conducted to explore the origin and chemotaxis mechanism of the immune cells. To investigate cell effects on SAH prognosis, murine neurological function was evaluated based on a modified Garcia score, pole test, and rotarod test., Results: The bioinformatics analysis confirmed that inflammatory and immune responses were the key pathophysiological processes after SAH. Significant increases in the monocyte levels were observed in both the mouse brains and the peripheral blood of patients after SAH. Ly6C-high monocytes originated in the bone marrow, and the skull bone marrow contribute a higher proportion of these monocytes than neutrophils. The mRNA level of Ccl2 was significantly upregulated after SAH and was greater in CD11b-positive than CD11b-negative cells. Microglial depletion, microglial inhibition, and CCL2 blockade reduced the numbers of Ly6C-high monocytes after SAH. With CCR2 antagonization, the neurological function of the mice exhibited a slow recovery. Three days post-SAH, the monocyte-derived dendritic cell (moDC) population had a higher proportion of TNF-α-positive cells and a lower proportion of IL-10-positive cells than the macrophage population. The ratio of moDCs to macrophages was higher on day 3 than on day 5 post-SAH., Conclusions: Inflammatory and immune responses are significantly involved in SAH-induced brain injury. Ly6C-high monocytes derived from the bone marrow, including the skull bone marrow, infiltrated into mouse brains via CCL2 secreted from microglia. Moreover, Ly6C-high monocytes alleviated neurological dysfunction after SAH., (© 2023. The Author(s).)

Background: The relationship between neutrophil to lymphocyte ratio (NLR) and poor outcome of aneurysmal subarachnoid hemorrhage (aSAH) is controversial. We aim to evaluate the relationship between NLR on admission and the poor outcome after aSAH., Method: Part I: Retrospective analysis of aSAH patients in our center. Baseline characteristics of patients were collected and compared. Multivariate analysis was used to evaluate parameters independently related to poor outcome. Receiver operating characteristic (ROC) curve analysis was used to determine the best cut-off value of NLR. Part II: Systematic review and meta-analysis of relevant literature. Related literature was selected through the database. The pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated to evaluate the correlation between NLR and outcome measures., Results: Part I:   A total of 240 patients with aSAH were enrolled, and 52 patients had a poor outcome. Patients with poor outcome at 3 months had a higher admission NLR, Hunt & Hess score, Barrow Neurological Institute (BNI) scale score, Subarachnoid Hemorrhage Early Brain Edema Score (SEBES), and proportion of hypertension history. After adjustment, NLR at admission remained an independent predictor of poor outcome in aSAH patients (OR 0.76, 95% CI 0.69-0.83; P < 0.001). The best cut-off value of NLR in ROC analysis is 12.03 (area under the curve 0.805, 95% CI 0.735 - 0.875; P < 0.001). Part II: A total of 16 literature were included. Pooled results showed that elevated NLR was significantly associated with poor outcome (OR 1.31, 95% CI 1.14-1.49; P < 0.0001) and delayed cerebral ischemia (DCI) occurrence (OR 1.32, 95% CI 1.11-1.56; P = 0.002). The results are more reliable in large sample sizes, low NLR cut-off value, multicenter, or prospective studies., Conclusion: Elevated NLR is an independent predictor of poor outcome and DCI occurrence in aSAH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guo, Liu, Zeng, Cai, Wang, Wu, Yu, Zheng, Chen, Peng, Yu, Yan, Cao and Chen.)

Neuroinflammation is a key process in the pathogenesis of subarachnoid hemorrhage (SAH) and contributes to poor outcome in patients. The purpose of this study is to explore the effect of triggering receptor expressed on myeloid cells 1 (TREM1) in the SAH, as well as its potential mechanism. In our study, plasma levels of soluble TREM1 was increased significantly after SAH and correlated to SAH severity and serum C-reactiveprotein. TREM1 inhibitory peptide LP17 alleviated the neurological deficits, attenuated brain water content, and reduced neuronal damage after SAH. Meanwhile, TREM1 inhibitory peptide decreased neuroinflammation (evidenced by the decreased levels of markers including IL-6, IL-1β, TNF-α) by attenuating proinflammatory subtype transition of microglia (evidenced by the decreased levels of markers including CD68, CD16, CD86) and decreasing the formation of neutrophil extracellular traps (evidenced by the decreased levels of markers including CitH3, MPO, and NE). Further mechanistic study identified that TREM1 can activate downstream proinflammatory pathways through interacting with spleen tyrosine kinase (SYK). In conclusion, inhibition of TREM1 alleviates neuroinflammation by attenuating proinflammatory subtype transition of microglia and decreasing the formation of neutrophil extracellular traps through interacting with SYK after SAH. TREM1 may be a a promising therapeutic target for SAH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wu, Zeng, Xu, Chen, Fan, Zhou, Yu, Fu, Peng, Yan, Yu and Chen.)

It has been reported that neutrophil extracellular traps (NETs) involve inflammation, coagulation and cell death. Acute lung injury is also considered to be connected with NETs. Deoxyribonuclease I (DNase-1), a clinical medication for the respiratory system, has been reported to degrade cell-free DNA (cfDNA), which is the main component of NETs. Herein, we did research to clarify the therapeutic value of DNase-1 in NPE after SAH. In this model, we found that the treatment of DNase-1 remarkably decreased lung water, neutrophilic infiltration and inflammation. In addition, DNase-1 inhibited the NETs and proinflammatory subtype transition of the macrophages. Moreover, the depletion of neutrophil also verified the role of NETs in NPE. Our results suggest that DNase-1 has the potential to effectively relieve the NPE after SAH and to be a clinical drug for use after SAH. [ABSTRACT FROM AUTHOR]

Aneurysmal subarachnoid hemorrhage (aSAH) is an important type of stroke with the highest rates of mortality and disability. Recent evidence indicates that neuroinflammation plays a critical role in both early brain injury and delayed neural deterioration after aSAH, contributing to unfavorable outcomes. The neutrophil-to-lymphocyte ratio (NLR) is a peripheral biomarker that conveys information about the inflammatory burden in terms of both innate and adaptive immunity. This review summarizes relevant studies that associate the NLR with aSAH to evaluate whether the NLR can predict outcomes and serve as an effective biomarker for clinical management. We found that increased NLR is valuable in predicting the clinical outcome of aSAH patients and is related to the risk of complications such as delayed cerebral ischemia (DCI) or rebleeding. Combined with other indicators, the NLR provides improved accuracy for predicting prognosis to stratify patients into different risk categories. The underlying pathophysiology is highlighted to identify new potential targets for neuroprotection and to develop novel therapeutic strategies. [ABSTRACT FROM AUTHOR]