Background: Stroke, including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage (SAH), remains a leading cause of mortality globally. Different stroke subtypes have similar detrimental effects in multiple fields of health. Previous research has shown that metformin plays a neuroprotective role in experimental animal models of stroke; however, a preclinical quantitative analysis on the ability of metformin to treat stroke is still lacking. This meta-analysis evaluates the efficacy of metformin in improving stroke prognosis in rodent models of stroke.Methods: Relevant preclinical trials were retrieved from PubMed, EMBASE, and the Web of Science. The neurological score (NS), brain water content (BWC), infarct size, rotarod test, TUNEL, neuron quantity, microglia quantity, and p-AMPK levels were compared between a control group and a metformin group using the standardized mean difference (SMD) and corresponding confidence interval (CI). Quality was assessed with SYRCLE’s risk of bias tool.Results: Fifteen articles published from 2010 to 2022 were included in the meta-analysis. The metformin group had statistically significant differences compared to the control group in the following aspects: NS (SMD −1.45; 95% CI −2.32, −0.58; p = 0.001), BWC (SMD −3.22; 95% CI −4.69, −1.76; p < 0.0001), infarct size (SMD −2.90; 95% CI −3.95, −1.85; p < 0.00001), rotarod test (SMD 2.55; 95% CI 1.87, 3.23; p < 0.00001), TUNEL (SMD -3.63; 95% CI −5.77, −1.48; p = 0.0009), neuron quantity (SMD 3.42; 95% CI 2.51, 4.34; p < 0.00001), microglia quantity (SMD −3.06; 95% CI -4.69, −1.44; p = 0.0002), and p-AMPK levels (SMD 2.92; 95% CI 2.02, 3.82; p < 0.00001). Furthermore, sensitivity analysis and stratified analysis were conducted for heterogeneous outcome indicators.Conclusion: Overall, metformin treatment improves severe outcomes triggered by stroke. Despite the limitations intrinsic to animal studies, this systematic review may provide a vital reference for future high-quality preclinical trials and clinical use.

Background: Resveratrol (RES) has a protective effect on acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Our purpose was to conduct a meta−analysis to investigate the efficacy of RES for ALI/ARDS in animal models.Methods: PubMed, EMBASE and Web of Science were searched to screen relevant preclinical trials. The standardized mean difference (SMD) was used to compare the lung injury score, lung wet−dry weight ratio (W/D ratio), tumor necrosis factor−α (TNF−α), interleukin−1β (IL−1β), IL−6, IL−10, the number of neutrophils in bronchoalveolar lavage fluid (BALF) and the total protein in BALF between the treatment and control groups. SYRCLE’s risk of bias tool was used for quality assessment.Results: A total of 17 studies published from 2005 to 2021 were included in our study to calculate the SMD with corresponding confidence interval (CI). As compared with controls, RES significantly decreased the lung injury score (SMD −2.06; 95% CI −2.77, −1.35; p < 0.00001) and W/D ratio (SMD −1.92; 95% CI −2.62, −1.22; p < 0.00001). RES also reduced the number of neutrophils in BALF (SMD −3.03; 95% CI −3.83, −2.24; p < 0.00001) and the total protein in BALF (SMD −5.59; 95% CI −10.10, −1.08; p = 0.02). Furthermore, RES was found to downregulate proinflammatory mediators such as TNF−α (SMD −2.02; 95% CI −3.09, −0.95; p = 0.0002), IL−1β (SMD −2.51; 95% CI −4.00, −1.02; p = 0.001) and IL−6 (SMD −2.26; 95% CI −3.49, −1.04; p = 0.0003). But RES had little effect on the anti−inflammatory mediators such as IL−10 (SMD 2.80; 95% CI −0.04, 5.63; p = 0.05). Sensitivity analysis and stratified analysis were performed for the outcome indicators with heterogeneity.Conclusion: RES treatment is effective on reducing the severity of ALI. However, more animal studies and human trials are needed for further investigation. Our study may provide a reference for preclinical and clinical studies in the future to some extent.

Traumatic brain injury (TBI) often results in persistent neurological dysfunction, which is closely associated with white matter injury. While the mechanisms underlying white matter injury after TBI remain unclear, recent research has implicated ferroptosis, a form of programmed cell death, in cognitive impairment after TBI. Ferritinophagy, a selective autophagic process that degrades ferritin and releases free iron. Here, we established a rat model of TBI and examined the expression of NCOA4, which mediates ferritin degradation through autophagy in lysosomes, to investigate whether ferritinophagy contributes to white matter injury after TBI. Our results showed that NCOA4 was overexpressed in the rat model of TBI, and knockdown of NCOA4 using shNCOA4 lentivirus infection inhibited ferroptosis induced by ferritinophagy. Furthermore, we found that treatment with ISRIB, a small molecule that selectively inhibits the integrated stress response, attenuated NCOA4-mediated ferritinophagy and improved white matter injury. These findings suggest that NCOA4-mediated ferritinophagy is a critical mechanism underlying white matter injury after TBI, and that ISRIB may hold promise as a therapeutic agent for treating this injury.

White matter damage (WMD), one of the research hotspots of subarachnoid hemorrhage (SAH), mainly manifests itself as myelin injury and oligodendrocyte differentiation disorder after SAH, although the specific mechanism remains unclear. Dexamethasone-induced Ras-related protein 1(Dexras1) has been reported to be involved in nervous system damage in autoimmune encephalitis and multiple sclerosis. However, whether Dexras1 participates in dysdifferentiation of oligodendrocytes and myelin injury after SAH has yet to be examined, which is the reason for creating the research content of this article. Here, intracerebroventricular lentiviral administration was used to modulate Dexras1 levels in order to determine its functional influence on neurological injury after SAH. Immunofluorescence, transmission electron microscopy, and Western blotting methods, were used to investigate the effects of Dexras1 on demyelination, glial cell activation, and differentiation of oligodendrocyte progenitor cells (OPCs) after SAH. Primary rat brain neurons were treated with oxyhemoglobin to verify the association between Dexras1 and cAMP-CREB. The results showed that Dexras1 levels were significantly increased upon in vivo SAH model, accompanied by OPC differentiation disturbances and myelin injury. Dexras1 overexpression significantly worsened OPC dysdifferentiation and myelin injury after SAH. In contrast, Dexras1 knockdown ameliorated myelin injury, OPC dysdifferentiation, and glial cell activation. Further research of the underlying mechanism discovered that the cAMP-CREB pathway was inhibited after Dexras1 overexpression in the in vitro model of SAH. This study is the first to confirm that Dexras1 induced oligodendrocyte dysdifferentiation and myelin injury after SAH by inhibiting the cAMP-CREB pathway. This present research may reveal novel therapeutic targets for the amelioration of brain injury and neurological dysfunction after SAH.

BackgroundBlood blister-like aneurysm (BBA) is a rare and special type of intracranial aneurysm with extremely high rates of rupture, morbidity, mortality, and recurrence. Willis Covered Stent (WCS) is a new device that is specifically designed for the treatment of intracranial complex aneurysms. However, the efficacy and safety of WCS treatment for BBA remain controversial. Thus, a high level of evidence is required to prove the efficacy and safety of WCS treatment.MethodsA systematic literature review was performed using a comprehensive literary search in Medline, Embase, and Web of Science databases to identify studies related to WCS treatment for BBA. A meta-analysis was then conducted to incorporate the efficacy and safety outcomes, including intraoperative situation, post-operative situation, and follow-up data.ResultsEight non-comparative studies containing 104 patients with 106 BBAs met the inclusion criteria. In the intraoperative situation, the technical success rate was 99.5% [95% confidence interval (CI), 0.958, 1.000], the complete occlusion rate was 98.2% (95% CI, 0.925, 1.000), and the side branch occlusion rate was 4.1% (95% CI, 0.001, 0.114). Vasospasm and dissection occurred in 9.2% (95% CI, 0.000, 0.261) and 0.1% (95% CI, 0.000, 0.032) of the patients, respectively. In the post-operative situation, the rebleed and mortality rates were 2.2% (95% CI, 0.000, 0.074) and 1.5% (95% CI, 0.000, 0.062), respectively. In the follow-up data, recurrence and parent artery stenosis occurred in 0.3% (95% CI, 0.000, 0.042) and 9.1% (95% CI, 0.032, 0.168) of the patients, respectively. Ultimately, 95.7% (95% CI, 0.889, 0.997) of the patients had a good outcome.ConclusionsWillis Covered Stent could be effectively and safely applied for BBA treatment. The results provide a reference for clinical trials in the future. Well-designed prospective cohort studies must be conducted for verification.