Background: Inflammation contributes to the poor prognosis of intracerebral hemorrhage (ICH). Intermittent fasting (IF) has been shown to be protective against inflammation in multiple pathogenic processes. In the present study, we aimed to investigated the beneficial effects of IF in attenuating neuroinflammation and neurological deficits in a mouse model of ICH and to investigate the underlying mechanism. Methods: ICH was modeled by intrastriatal injection of autologous blood and IF was modeled by every-other-day feeding in male control mice (C57BL/6), mice with and microglia specific knockout Sirt3^f/f;Cx3cr1-Cre (Sirt3 cKO), and Sirt3^f/f (wild-type) mice. Brain tissues and arterial blood were harvested at 1, 3, 7 and 28 days after ICH for immunohistochemistry analysis of Iba-1, DARPP-32 and HO-1, morphological analysis by HE staining and inflammatory factor release tests by ELISA. Neurological functions were approached by corner test and cylinder test. Fluorescent double-labeled staining of Iba-1 with CD16, Arg1 or Sirt3 was used to provide direct image of co-expression of these molecules in microglia. TUNEL, cleaved caspase-3 and Nissl staining was performed to evaluate cellular injuries. Results: IF alleviated neurological deficits in both acute and chronic phases after ICH. Morphologically, IF enhanced hematoma clearance, reduced brain edema in acute phase and attenuated striatum atrophy in chronic phase. In addition, IF decreased the numbers of TUNEL⁺ cells and increased Nissl⁺ neuron number at day 1, 3 and 7 after ICH. IF suppressed CD16⁺Iba-1⁺ microglia activation at day 3 after ICH and reduced inflammatory releases, such as IL-1β and TNF-α. The above effects of IF were attenuated by microglia Sirt3 deletion partly because of an inhibition of Nrf2/HO-1 signaling pathway. Interestingly, IF increased Iba-1⁺ microglia number at day 7 which mainly expressed Arg1 while decreased the proinflammatory factor levels. In mice with microglia-specific Sirt3 deletion, the effects of IF on Iba-1⁺ microglia activation and anti-inflammatory factor expressions were attenuated when compared with wild-type Sirt3^f/f mice. Conclusions: IF protects against ICH by suppressing the inflammatory responses via the Sirt3/Nrf2/HO-1 pathway.

Shank3, a key molecule related to the development and deterioration of autism, has recently been found to downregulate in the murine brain after ischemia/reperfusion (I/R). Despite this discovery, however, its effects on neuronal injury and the mechanism underlying the effects remain to be clarified. To address this, in this study, based on genetically modified mice models, we revealed that the expression of Shank3 showed a time-dependent change in murine hippocampal neurons after I/R, and that conditional knockout (cko) of Shank3 in neurons resulted in aggravated neuronal injuries. The protective effects of Shank3 against oxidative stress and inflammation after I/R were achieved through direct binding STIM1 and subsequent proteasome-mediated degradation of STIM1. The STIM1 downregulation induced the phosphorylation of downstream Nrf2 Ser40, which subsequently translocated to the nucleus, and further increased the expression of antioxidant genes such as NQO1 and HO-1 in HT22 cells. In vivo, the study has further confirmed that double knockout of Shank3 and Stim1 alleviated oxidative stress and inflammation after I/R in Shank3^cko mice. In conclusion, the present study has demonstrated that Shank3 interacts with STIM1 and inhibits post-I/R neuronal oxidative stress and inflammatory response via the Nrf2 pathway. This interaction can potentially contribute to the development of a promising method for I/R treatment.

Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude sickness. Autophagy plays a critical role in ischemic brain injury, but its role in hypobaric hypoxia (HH) remains unknown. Here we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain, and is partially responsible for HH-induced oxidative stress, neuronal loss, and brain damage. The autophagic agonist rapamycin only promotes the initiation of autophagy. By proteome analysis, a screen showed that protein dynamin2 (DNM2) potentially regulates autophagic flux. Overexpression of DNM2 significantly increased the formation of autolysosomes, thus maintaining autophagic flux in combination with rapamycin. Furthermore, the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH exposure. These results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.

Background: Although most unruptured intracranial aneurysms (UIAs) have good prognosis after flow diverter (FD) treatment, some remain unoccluded for extended periods, posing a persistent rupture risk. This study aims to develop a predictive model for UIA occlusion after FD treatment through integrating morphological and hemodynamic parameters, which may be critical for personalized postoperative management. Methods: Data from patients with single UIAs treated with stand‐alone FD were collected from June 2018 to December 2022 in four cerebrovascular disease centers. Morphological parameters were obtained from 3D reconstructed aneurysm models, and hemodynamic parameters were derived by computational fluid dynamics (CFD) analysis. A predictive model for aneurysm occlusion was constructed using various machine learning algorithms, including logistic regression, Random Forest, XGBoost, and K‐Nearest Neighbors. Model performances were evaluated through repeated cross‐validation, 0.632 bootstrap, and 0.632+ bootstrap. Shapley additive explanation (SHAP) analysis was employed to assess the contribution of each parameter to UIA occlusion. Results: Seventy‐nine patients were reviewed; a total of 51 cases met the criteria, with an average age of 53.9 ± 9.9 years. The average aneurysm diameter was 3.72 ± 2.72 mm, comprising 29 occlusions and 22 non‐occlusions. Five variables were selected for further modeling, including follow‐up time > 6 months, aneurysm rupture ratio (ArR), occlusion ratio (OsR), parent artery wall shear stress (WSS), and the change of parent artery WSS. Logistic regression outperformed other algorithms, achieving an area under the curve (AUC) above 0.75, indicating good predictive performance. SHAP analysis revealed that the change of parent artery WSS contributed most significantly to accurate and early prediction. Additionally, a web application software was developed to assist clinicians in real‐time aneurysm occlusion prediction. Conclusions: This study developed a robust predictive model for UIA occlusion following FD treatment by integrating morphological and hemodynamic parameters, which may provide potentially valuable decision‐making support for optimizing treatment strategies.

Intracranial aneurysms (IAs), as a common cerebrovascular disease, claims a worldwide morbidity rate of 3.2%. Inflammation, pivotal in the pathogenesis of IAs, influences their formation, growth, and rupture. This review investigates aspirin's modulation of inflammatory pathways within this context. With IAs carrying significant morbidity and mortality upon IAs rupture and current interventions limited to surgical clipping and endovascular coiling, the quest for pharmacological options is imperative. Aspirin's role in cardiovascular prevention, due to its anti-inflammatory effects, presents a potential therapeutic avenue for IAs. In this review, we examine aspirin's efficacy in experimental models and clinical settings, highlighting its impact on the progression and rupture risks of unruptured IAs. The underlying mechanisms of aspirin's impact on IAs are explored, with its ability examined to attenuate endothelial dysfunction and vascular injury. This review may provide a theoretical basis for the use of aspirin, suggesting a promising strategy for IAs management. However, the optimal dosing, safety, and long-term efficacy remain to be established. The implications of aspirin therapy are significant in light of current surgical and endovascular treatments. Further research is encouraged to refine aspirin's clinical application in the management of unruptured IAs, with the ultimate aim of reducing the incidence of aneurysms rupture.