Evidence indicates that neutrophil has promoted inflammation in several central nervous system diseases. However, whether the peripheral blood levels of neutrophils are associated with the functional outcome after subarachnoid hemorrhage and its potential mechanism remain unclear. In this study, we showed that neutrophil levels in peripheral blood were higher in patients with subarachnoid hemorrhage ( P < 0.001) than in healthy subjects. Neutrophil levels were positively associated with Hunt and Hess grade ( P < 0.001) and modified Rankin Scale scores at 3 months after SAH ( P = 0.008). In terms of the mechanism, neutrophil extracellular traps markedly increased the proinflammatory subtype transition of microglia. After treatment with DNAse I, the proinflammatory subtype transition of microglia involving CD16 positive and IL-1β positive microglia was limited ( P < 0.05). This mechanism was also verified in vitro . These results indicate that the existence of neutrophil extracellular traps, released from neutrophils after subarachnoid hemorrhage, can shift microglia toward a more proinflammatory phenotype and contribute to neuroinflammation and poor outcome in subarachnoid hemorrhage.

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.

It has been reported that several immune cells can release chromatin and granular proteins into extracellular space in response to the stimulation, forming extracellular traps (ETs). The cells involved in the extracellular trap formation are recognized including neutropils, macrophages, basophils, eosinophils, and mast cells. With the development of research related to central nervous system, the role of ETs has been valued in neuroinflammation, blood–brain barrier, and other fields. Meanwhile, it has been found that microglial cells as the resident immune cells of the central nervous system can also release ETs, updating the original understanding. This review aims to clarify the role of the ETs in the central nervous system, especially in neuroinflammation and blood–brain barrier.

Objective: To evaluate the efficacy and safety of tirofiban for patients with acute ischemic stroke (AIS), especially posterior circulation stroke (PCS).Methods: We enrolled consecutive patients with AIS who suffered large artery occlusion (LAO) and underwent mechanical thrombectomy (MT) between January 2016 and May 2020. Patients were divided into two groups according to whether tirofiban was used during MT. The primary efficacy outcome was a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0–2 at 3 months. The safety outcomes were the rate of mortality at 3 months and the presence of intracranial hemorrhage (ICH) and symptomatic intracranial hemorrhage (sICH). Cohorts were balanced using 1:1 propensity score matching (PSM). Subgroup analysis was further performed to compare the efficacy and safety of tirofiban between the anterior circulation stroke (ACS) and PCS groups.Results: A total of 292 patients were eligible for this study and divided into the tirofiban group (n = 51) and the no-tirofiban group (n = 241). In the propensity-score-matched cohort, the tirofiban group had a higher rate of favorable outcomes than the no-tirofiban group (49.0 vs. 25.5%, p = 0.014), and the mortality at 3 months showed a greater downward trend in the tirofiban group than the no-tirofiban group (15.6 vs. 33.3% p = 0.064). The risk of sICH and ICH was the same between the tirofiban and control groups (17.6 vs. 27.4% p = 0.236, 31.3 vs. 45.1% p = 0.154, respectively). Tirofiban use was predictive of favorable outcomes [adjusted odds ratio (aOR) = 2.87, 95% confidence interval (CI) 1.52–6.44, p = 0.043] after multiple logistic regression analysis. Subgroup analysis revealed that tirofiban use was significantly associated with favorable outcomes in ACS (aOR = 3.66, 95% CI 1.24–5.22, p = 0.019) but not in PCS (aOR = 1.12, 95% CI 0.47–7.52, p = 0.570).Conclusion: We demonstrated that tirofiban may be associated with improving favorable outcome for the AIS patients who underwent MT, without increasing ICH or sICH. Furthermore, our results indicated that for PCS patients tirofiban may not be associated with favorable outcome, and more comprehensive randomized controlled trials are needed to confirm this finding.

BackgroundThe 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.MethodPart 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.ResultsPart 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 &amp; 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 &lt; 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 &lt; 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 &lt; 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.ConclusionElevated NLR is an independent predictor of poor outcome and DCI occurrence in aSAH.