BACKGROUND:Myocardial ischemia/reperfusion (I/R) injury induces an intense inflammatory response and involves multiple cell death pathways. PANoptosis, an integrated cell death process involving pyroptosis, apoptosis and necroptosis, is a major driver of cardiomyocyte loss during I/R injury. However, the epitranscriptomic control of PANoptosis is poorly understood. METHODS:We investigated the role of ALKBH3, an mRNA N1-methyladenosine (m1A) demethylase, in the regulation of cardiomyocyte PANoptosis using hypoxia/reoxygenation models in vitro and murine I/R models in vivo. Integrated transcriptomic and m1A epitranscriptomic profiling identified downstream targets. Loss- and gain-of-function studies of ALKBH3, AIM2, ZBED6 and STAT1 (siRNA or plasmid overexpression) were coupled with assessments of cell death phenotypes, inflammasome activity and gene expression. Molecular interactions and transcriptional/translational regulation were examined using co-immunoprecipitation, chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. RESULTS:Cardiomyocyte-restricted ALKBH3 overexpression mitigates I/R injury in vivo. Mechanistically, ALKBH3 acts as a key suppressor of PANoptosis by inhibiting AIM2. ALKBH3 demethylates m1A onZBED6 mRNA, enhancing ZBED6 translation and limiting cardiomyocyte PANoptosis. Although ZBED6 does not bind directly to the AIM2 promoter, it physically interacts with STAT1, a transcriptional activator of AIM2, and represses STAT1-driven AIM2 expression. ZBED6 overexpression reduces AIM2 levels and PANoptosis, whereas AIM2 knockout attenuates the exacerbation of cardiac injury and PANoptosis induced by ALKBH3 silencing. CONCLUSIONS:These findings identify the ALKBH3/ZBED6/STAT1/AIM2 signalling axis that epitranscriptomically breaks cardiomyocyte PANoptosis, highlighting a tractable therapeutic target that limits cell death and improves myocardial outcomes after I/R.

Cardiac fibroblasts progressively replace deceased cardiomyocytes during the development of myocardial fibrosis, an irreversible pathological repair process that ultimately leads to cardiac dysfunction and heart failure. Cardiac injury was evaluated by echocardiography and Masson staining in myocardial infarction (MI) mice with zinc finger BED-type containing 6 (ZBED6) knockdown or overexpression. Furthermore, chromatin immunoprecipitation (ChIP) assays, electrophoretic mobility shift assays (EMSAs), and luciferase reporter assays were used to explore the target of ZBED6. ZBED6 expression was notably decreased in vivo in MI hearts and in vitro in TGF-β-induced primary mouse cardiac fibroblasts (PMCFs). Transgenic overexpression of ZBED6 specifically in cardiac fibroblasts improved cardiac dysfunction, reduced the infarct area, and decreased the expression levels of fibrotic genes after MI injury. Conversely, physiological knockdown of ZBED6 induced cardiac dysfunction and remodeling, which is consistent with the phenomena observed in vitro. Mechanistically, ZBED6, which functions as a transcriptional inhibitor of Piezo1, failed to prevent its transcription owing to mutations in the promoter binding sites. Stimulation of Piezo1 in PMCFs facilitates YAP translocation into the nucleus, whereas knockdown of Piezo1 or the use of a Piezo1 inhibitor suppresses this translocation. Moreover, the activation of Piezo1 reversed the cardioprotective effects of ZBED6 overexpression. In summary, the protective effect of ZBED6 against myocardial fibrosis injury is achieved through the inhibition of Piezo1 transcription, leading to reduced YAP nuclear translocation. These findings suggest that ZBED6 may become a potential therapeutic target for the clinical treatment of myocardial fibrosis.

Background: Glioblastoma is the most common type of brain cancer, with a prognosis that is unfortunately poor. Despite considerable progress in the field, the intricate molecular basis of this cancer remains elusive. Aim: The aim of this study was to identify genetic indicators of glioblastoma and reveal the processes behind its development. Objective: The advent and integration of supercomputing technology have led to a significant advancement in gene expression analysis platforms. Microarray analysis has gained recognition for its pivotal role in oncology, crucial for the molecular categorization of tumors, diagnosis, prognosis, stratification of patients, forecasting tumor responses, and pinpointing new targets for drug discovery. Numerous databases dedicated to cancer research, including the Gene Expression Omnibus (GEO) database, have been established. Identifying differentially expressed genes (DEGs) and key genes deepens our understanding of the initiation of glioblastoma, potentially unveiling novel markers for diagnosis and prognosis, as well as targets for the treatment of glioblastoma. Methods: This research sought to discover genes implicated in the development and progression of glioblastoma by analyzing microarray datasets GSE13276, GSE14805, and GSE109857 from the GEO database. DEGs were identified, and a function enrichment analysis was performed. Additionally, a protein-protein interaction network (PPI) was constructed, followed by module analysis using the tools STRING and Cytoscape. Results: The analysis yielded 88 DEGs, consisting of 66 upregulated and 22 downregulated genes. These genes' functions and pathways primarily involved microtubule activity, mitotic cytokinesis, cerebral cortex development, localization of proteins to the kinetochore, and the condensation of chromosomes during mitosis. A group of 27 pivotal genes was pinpointed, with biological process analysis indicating significant enrichment in activities, such as division of the nucleus during mitosis, cell division, maintaining cohesion between sister chromatids, segregation of sister chromatids during mitosis, and cytokinesis. The survival analysis indicated that certain genes, including PCNA clamp-associated factor (PCLAF), ribonucleoside- diphosphate reductase subunit M2 (RRM2), nucleolar and spindle-associated protein 1 (NUSAP1), and kinesin family member 23 (KIF23), could be instrumental in the development, invasion, or recurrence of glioblastoma. Conclusion: The identification of DEGs and key genes in this study advances our comprehension of the molecular pathways that contribute to the oncogenesis and progression of glioblastoma. This research provides valuable insights into potential diagnostic and therapeutic targets for glioblastoma.

Liver cancer is a highly aggressive malignancy with poor survival rates. Current treatments, including liver transplantation, immunotherapy, and gene therapy, are often limited by late-stage diagnosis and significant side effects, highlighting the urgent need for novel therapeutic agents. In this study, we evaluated the therapeutic potential of Kanglexin (KLX), a novel anthraquinone derivative, in the treatment of liver cancer. In vitro, KLX inhibited the proliferation and migration of HepG2 and Hep3B cells in a dose-dependent manner. Mechanistically, KLX upregulated Z-DNA binding protein 1 (ZBP1) expression, inducing PANoptosis by directly binding to ZBP1, altering its conformation, and reducing its affinity for the E3 ubiquitin ligase ring finger protein 180 (RNF180). This interaction decreased ZBP1 ubiquitination, thereby increasing its stability. Additionally, KLX upregulated the expression of the transcription factor homeobox D10 (HOXD10), which further increased ZBP1 expression. Elevated ZBP1 levels significantly suppressed liver cancer cell proliferation and migration, whereas the inhibitory effects of KLX were reversed upon ZBP1 knockdown. In a xenograft model, KLX significantly inhibited tumor growth with a lower toxicity than oxaliplatin (OXA). In conclusion, KLX promoted PANoptosis in liver cancer cells by upregulating ZBP1 and preventing its degradation, thereby inhibiting liver cancer progression and migration. These findings suggest that KLX is a promising therapeutic agent for liver cancer.

Liver fibrosis is a pathological response following liver injury induced by various etiologies. Herein, we present the therapeutic potential of a novel anthraquinone compound, kanglexin (KLX), in the treatment of liver fibrosis. We observed significant suppression of the inflammatory response and extracellular matrix deposition in mice with liver fibrosis induced by CCL4, by bile duct ligation, and by a methionine-choline-deficient diet. Mechanistically, through screening, we found that KLX interacts with HDAC1. Additionally, KLX facilitates binding between HDAC1 and KCTD11, promoting the ubiquitination-mediated degradation of HDAC1 and consequently reducing its protein level. Moreover, HDAC1 was found to bind to PPARγ, influencing its acetylation level. Following KLX treatment, the level of PPARγ deacetylation mediated by HDAC1 decreases, leading to increased protein expression of PPARγ. This effectively inhibited the NFκB and TGF-β/Smad2/3 signaling pathways, thereby reducing inflammation and extracellular matrix deposition. Ultimately, this intervention can halt the progression of liver fibrosis and ameliorate liver damage. In summary, our study demonstrated that KLX can effectively inhibit the progression of liver fibrosis by modulating the protein level and activity of HDAC1. These findings provide valuable insights for the development of effective drugs and treatment strategies for liver fibrosis.

Objective To explore the technical key points, clinical efficacy and safety of hybrid operation for symptomatic chronic common carotid artery occlusion (CCAO). Methods and Results A total of 10 patients with symptomatic chronic CCAO who underwent hybrid operation in The First Affiliated Hospital of Harbin Medical University from December 2022 to October 2024 were included. The median preoperative modified Rankin Scale (mRS) score was 2 (1, 2). All patients successfully completed revascularization with a technical success rate of 10/10, including 6 cases treated with carotid endarterectomy (CEA) combined with retrograde transcarotid recanalization (for patients with short CCA residual stumps) and 4 cases treated with CEA combined with antegrade transfemoral recanalization (for patients with long CCA residual stumps). Postoperative complications included one case of cerebral hyperperfusion syndrome (CHS), with no occurrence of neck hematoma, hemorrhagic stroke, ischemic stroke or transient ischemic attack. During a median follow-up of 10 (9, 12) months, there were no cases of restenosis requiring retreatment, ipsilateral ischemic stroke or transient ischemic attack. The median mRS score at last follow-up was 0 (0, 1). The last follow-up mRS score was lower than the preoperative mRS score (Z = - 0.289, P = 0.004). Conclusions The hybrid operation is safe and effective for treating symptomatic chronic CCAO. In clinical practice, CEA combined with retrograde transcarotid recanalization may demonstrate relatively significant advantages for symptomatic chronic CCAO with shorter residual stumps, potentially facilitating more optimal revascularization outcomes. However, further case validation remains necessary.

Ischaemic heart disease is an important cause of death in humans, and resupply of blood to damaged myocardium can exacerbate the risk of cardiac I/R injury. Circular RNAs (circRNAs) play an important role in cardiovascular disease. In this study we investigated the regulatory role of circDhx32 in the progression of I/R injury. Cardiac I/R model was established in mice by ligating the left anterior descending coronary artery (LAD) for 45 min, followed by blood reperfusion for 24 h or 2 weeks. For in vitro study, neonatal mouse ventricular cardiomyocytes were subjected to hypoxia-reoxygenation (H/R) assault. CircDhx32 was significantly upregulated in I/R-treated mice and H/R-treated cardiomyocytes. Cardiomyocyte-specific knockdown of circDhx32 ameliorated the pathological outcomes of cardiac I/R injury including improved cardiac function, reduced infarct size and reduced release of cardiac injury biomarkers. The protective effects of circDhx32 silencing were also observed in cardiomyocytes after H/R. We demonstrated that ALKBH5 functioned as an m6A demethylase, removing the m6A modification sites of circDhx32. Reduced m6A modification inhibited recognition and binding by the m6A readers YTHDF2 and YTHDC1, leading to circDhx32 degradation and diminished nucleoplasmic export under pathological conditions. Elevated circDhx32 inhibited the transcriptional activation of AdipoR1 by binding to FOXO1. Conversely, circDhx32 deficiency alleviated the inflammatory responses in I/R-treated mice and H/R-treated cardiomyocytes including decreased mRNA expression levels and release of inflammatory cytokines such as IL-6, TNF-α and IL-1β potentially through modulation of the AdipoR1-AMPK-NF-κB signaling pathway. In conclusion, ALKBH5 acted as m6A eraser accompanied by the m6A readers YTHDF2 and YTHDC1 to promote high expression and nuclear retention of circDhx32 under pathological conditions. CircDhx32 regulated the inflammatory responses to cardiac I/R injury by targeting the AdipoR1-AMPK-NF-κB signaling pathway, which competed with AdipoR1 for FOXO1. These results reveal a novel mechanism underlying cardiac ischaemic injury, and circDhx32 is expected to be a potential therapeutic target for early intervention in ischaemic cardiac disease.

Long non-coding RNAs (lncRNAs) are a complex and diverse group of transcripts, typically longer than 200 nucleotides, which do not encode proteins but play crucial roles in regulating gene expression. They exert their influence through various mechanisms, such as interacting with DNA, mRNA, and proteins, which allows them to modulate a wide array of biological processes. Recent studies have underscored the importance of lncRNAs in the development of the nervous system and the pathogenesis of neurological diseases, particularly in the context of hypoxic-ischemic brain injury. Hypoxic-ischemic brain injury, caused by reduced blood flow and oxygen supply to the brain, is a leading cause of long-term neurological deficits. This review delves into the emerging role of lncRNAs in hypoxic-ischemic brain injury, exploring how these non-coding RNAs influence critical molecular and cellular pathways involved in the brain's response to hypoxia-ischemia. Notable advancements, such as the identification of lncRNAs, like BC088414 and FosDT, highlight their dual roles as mediators of injury and potential therapeutic targets. Additionally, we discuss the feasibility of lncRNAs as biomarkers for early diagnosis and prognosis of hypoxic-ischemic brain injury. Despite these advancements, challenges remain in translating lncRNA research into clinical applications. Issues, such as delivery mechanisms, off-target effects, and the ethical considerations surrounding gene modulation, must be addressed. By synthesizing current research, this review aims to provide a comprehensive understanding of the multifaceted roles of lncRNAs in hypoxic-ischemic brain injury, paving the way for future research and novel therapeutic strategies targeting these non-coding RNAs in neurological disorders.

Metabolic dysfunction‐associated steatotic liver disease (MASLD) is among the most prevalent chronic liver diseases worldwide. The expression of YTH domain‐containing protein 1 (YTHDC1) is significantly reduced in patients and mouse models with MASLD. Hepatocyte‐specific knockout of YTHDC1 exacerbates HFD‐induced hepatic lipid accumulation. Lactate accumulation and enhanced arginyl‐tRNA synthetase 1 (AARS1)‐mediated K565‐specific lactylation are shown to drive the ubiquitination‐mediated degradation of YTHDC1. This work proposes that under MASLD conditions, diminished YTHDC1‐LDHA binding elevates free LDHA levels, which enhances YTHDC1 lactylation and suppresses its expression. This creates a positive feedback loop that exacerbates the progression of MASLD. Mechanistically, protein tyrosine phosphatase nonreceptor type 22 (PTPN22), identified as a downstream target of YTHDC1, exacerbates hepatic inflammation and lipid accumulation by dephosphorylating and activating NLRP3 at tyrosine 861, which in turn promotes the release of IL‐1β and IL‐18. Furthermore, mebendazole, a small‐molecule drug targeting YTHDC1, significantly alleviates MASLD. In conclusion, YTHDC1 mitigates MASLD by inhibiting the PTPN22‐mediated dephosphorylation and activation of NLRP3, offering new insights into therapeutic strategies for MASLD.

patients, with a follow-up rate of 81.3% (139/171) and amedian follow-up time of 8 months (interquartile range 6e12). During this period, 9 patients experienced aneurysmrecanalization, and the complete occlusion rate was 85.6%(119/139).-CONCLUSION:Endovascular treatment is feasible andeffective for treating ruptured intracranial aneurysms;however, there are still risks of complications and unfa-vorable clinical outcomes. The involvement of the basilarartery trunk increases the risk of complications, and theuse of closed cell design laser cut stents is associatedwith unfavorable outcomes. Clinicians should be cautiousto avoid the risk factors when treating ruptured posteriorcirculation aneurysms and strive to minimize the occur-rence of complications and unfavorable clinical outcomes patients, with a follow-up rate of 81.3% (139/171) and amedian follow-up time of 8 months (interquartile range 6e12). During this period, 9 patients experienced aneurysmrecanalization, and the complete occlusion rate was 85.6%(119/139). CONCLUSION:Endovascular treatment is feasible andeffective for treating ruptured intracranial aneurysms;however, there are still risks of complications and unfa-vorable clinical outcomes. The involvement of the basilarartery trunk increases the risk of complications, and theuse of closed cell design laser cut stents is associatedwith unfavorable outcomes. Clinicians should be cautiousto avoid the risk factors when treating ruptured posteriorcirculation aneurysms and strive to minimize the occur-rence of complications and unfavorable clinical outcomes

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, for the MTT assay experiments shown in Fig. 2A on p. 1655, the GDC‑0152/ANGPTL2 panel appeared to overlap with the ANGPTL2 panel, albeit the panel had been rotated through 180°; moreover, the magnification of the right‑hand panel was very different, creating an impression that the ANGPTL2 panel showed more cells. Upon analyzing the data independently in the Editorial Office, it came to light that that certain of the flow cytometric data in Fig. 2B and the nuclear staining experiments in Fig. 2C were strikingly similar to data in other articles written by different authors at different research institutes that had already been accepted for publication elsewhere. Owing to the fact that the contentious data in the above article had already been published prior to its submission to International Journal of Oncology, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 46: 1651‑1658, 2015; DOI: 10.3892/ijo.2015.2872].

Background:Intracranial vertebral artery stenosis is a significant cause of ischemic stroke. Intravascular optical coherence tomography (OCT), known for its high resolution, can accurately analyze the microstructure components of the stenotic vessel wall. Although widely used in the cardiovascular system, its application in intracranial atherosclerotic diseases of intracranial arteries remains limited. This study aimed to utilize OCT as a novel imaging modality for vessel wall microstructure analysis in patients with intracranial atherosclerosis. Specifically, it analyzed the vascular walls of 15 patients with severe intracranial vertebrobasilar artery stenosis before and after endovascular stent treatment. Methods:A retrospective analysis was conducted from 7 March 2023 to 26 March 2024 at The First Affiliated Hospital of Harbin Medical University, focusing on the neurosurgical endovascular stent treatment and OCT evaluation of 15 cases of intracranial vertebrobasilar artery stenosis (70-90%). All lesions were located in the V4 segment of the vertebral artery. Results:OCT accurately identified the vessel wall microstructures in patients with intracranial vertebrobasilar artery stenosis before and after endovascular stent treatment. Identified structures included fibrous plaques, lipid plaques, calcified plaques, ruptured plaques, intraluminal thrombosis, vascular dissection, microchannels, macrophages, cholesterol crystals, healing plaques, tissue prolapse, stent thrombosis, and stent adherence. Following endovascular stent treatment and OCT only one patient experienced symptomatic complications. Conclusions:The evaluation of intracranial vertebrobasilar arteries using OCT was shown to be safe and feasible. This technique aids in the diagnosis and treatment of cerebrovascular diseases. However, this preliminary study should be validated through prospective large-scale studies.

: Hypertension (HTN) is a leading risk factor for cardiovascular diseases (CVDs) and a major contributor to global morbidity and mortality. Conventional pharmacological treatments have been effective but are often accompanied by side effects and do not address all pathological aspects of the disease. Recent advances in molecular biology have identified non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), as key regulators in the pathogenesis of hypertension. These ncRNAs influence various cellular processes, such as gene expression, vascular tone, and inflammation, making them promising targets for therapeutic intervention. This review explores the potential of polyphenols, a diverse group of phytochemicals with potent antioxidant and anti-inflammatory properties, in modulating ncRNA expression and function. We discuss how polyphenols, such as epigallocatechin-3-gallate (EGCG), resveratrol, curcumin, and quercetin impact the regulation of ncRNAs, particularly focusing on their roles in reducing oxidative stress, improving endothelial function, and ameliorating vascular remodeling associated with hypertension. The review synthesizes current evidence from both in vitro and in vivo studies, highlighting significant findings and the mechanisms by which polyphenols exert their effects on ncRNA-mediated pathways. : Moreover, we address the challenges of translating these findings into clinical applications, including issues related to bioavailability, dosing, and the complex interactions of polyphenols with other cellular components. Future directions for research are suggested, with an emphasis on the need for comprehensive clinical trials to establish the efficacy of polyphenol-based therapies targeting ncRNAs in hypertension management. By targeting ncRNAs, polyphenols offer a novel therapeutic strategy that could enhance the treatment landscape for hypertension and potentially other cardiovascular conditions.

Symptomatic intracranial atherosclerotic stenosis (ICAS) is a major cause of ischemic stroke worldwide. In patients undergoing endovascular treatment for ICAS, in-stent restenosis (ISR) is associated with ischemic stroke recurrence. Intracranial drug-eluting self-expanding stent systems (COMETIU; Sinomed Neurovita Technology Inc., CHN) are new devices for treating ICAS. This study evaluated the perioperative experience and medium-term outcomes of COMETIU in 16 patients. We prospectively analyzed 16 patients with ICAS (≥ 70

BACKGROUND AND PURPOSE:As a chronic metabolic syndrome, hyperlipidaemia is manifested as aberrantly elevated cholesterol and triglyceride (TG) levels, primarily attributed to disorders in lipid metabolism. Despite the promising outlook for hyperlipidaemia treatment, the need persists for the development of lipid-lowering agents with heightened efficiency and minimal toxicity. This investigation aims to elucidate the lipid-lowering effects and potential pharmacodynamic mechanisms of Anti-b, a novel low MW compound. EXPERIMENTAL APPROACH:We employed high-fat diet (HFD) in hamsters and mice or oleic acid (OA) in cultures of HepG2 cells and LO2 cells to induce hyperlipidaemia models. We administered Anti-b to assess its therapeutic effects on dyslipidaemia and hepatic steatosis. We used western blotting, RNA sequencing, GO and KEGG analysis, oil red O staining, along with molecular docking and molecular dynamics simulation to elucidate the mechanisms underlying the effects of Anti-b. KEY RESULTS:Anti-b exhibited a substantial reduction in HFD-induced elevation of blood lipids, liver weight to body weight ratio, liver diameter and hepatic fat accumulation. Moreover, Anti-b demonstrated therapeutic effects in alleviating total cholesterol (TC), TG levels, and lipid accumulation derived from OA in HepG2 cells and LO2 cells. Mechanistically, Anti-b selectively bound to the mTOR kinase protein and increased mTOR thermal stability, resulting in downregulation of phosphorylation level. Notably, Anti-b exerted anti-hyperlipidaemia effects by modulating PPARγ and SREBP1 signalling pathways and reducing the expression level of mSREBP1 and PPARγ proteins. CONCLUSION AND IMPLICATIONS:In conclusion, our study has provided initial data of a novel low MW compound, Anti-b, designed and synthesised to target mTOR protein directly. Our results indicate that Anti-b may represent a novel class of drugs for the treatment of hyperlipidemia and hepatic steatosis.

Aims: Myocardial ischemia-reperfusion (I/R) injury facilitates cardiomyocyte death and endangers human health. N6-methyladenosine (m6A) methylation plays a critical role in cardiovascular diseases. The m6A reader YTHDF2 identifies m6A-modified RNA and promotes target RNA degradation. Hence, we hypothesized that YTHDF2 affects I/R injury by regulating RNA stability. Results: Both mRNA and protein levels of YTHDF2 were upregulated in I/R mice and hypoxia-reoxygenation (H/R)-induced cardiomyocytes. Silencing of endogenous YTHDF2 abrogated cardiac dysfunction and lowered the infarct size in I/R mice, and forced expression of YTHDF2 aggravated these adverse pathological processes. Consistently, the protective effect of silencing YTHDF2 occurred in cardiomyocytes exposed to H/R and erastin. Furthermore, RNA-seq and RIP revealed that YTHDF2 recognized the m6A modification sites of the ferroptosis-related gene SLC7A11 mRNA to promote its degradation both in vivo and in vitro. Inhibition of SLC7A11 impaired cardiac function, increased infarct size, and the release of LDH in I/R mice after silencing YTHDF2. The beneficial effects of si-YTHDF2 on H/R injury were reversed by co-transfection with si-SLC7A11, which substantially exacerbated ferroptosis and the production of ROS. Innovation and conclusion: The cardioprotective effects of silencing YTHDF2 are accomplished by increasing SLC7A11 stability and expression and reducing ferroptosis, providing novel potential therapeutic targets for treating ischemic cardiac diseases.

The mammalian target of rapamycin (mTOR) was reported to regulate cell autophagy and outcomes of several neurological diseases. Mitochondria, which serve as critical organelles in neurons. are also involved in the pathology of neurological diseases. However, the role of mTOR in mitochondrial morphology has not been clarified especially in subarachnoid hemorrhage (SAH). In this study, we established SAH models both in vivo and in vitro. Rapamycin and 3-methyl adenine (3-MA) were then administered to alter mTOR activity. Post-SAH assessment included SAH grading, neurological evaluation, blood–brain barrier (BBB) permeability, brain water content, mitochondrial membrane potential (MMP), mitochondrial morphology, ATP content, cell viability, cytotoxicity, and expression of proteins related to apoptosis and mitochondrial fission. The results showed that (1) neurological deficits, BBB permeability, and brain edema were increased after SAH and that cell viability was exacerbated in brain tissue. (2) Excessive mitochondrial fission was evident based on changes in mitochondrial morphology, while MMP and ATP content were decreased in neurons after SAH. (3) Administration of rapamycin improved the excessive mitochondrial fission and restored mitochondrial function, which subsequently reduced apoptosis. (4) 3-MA showed an adverse effect on mitochondria and aggravated excessive mitochondrial fission and dysfunction in SAH. Neurological deficits and neuronal viability were also exacerbated following the administration of 3-MA. Therefore, our study suggests that mTOR inhibition has neuroprotective effects against neuronal injury after SAH via alleviating excessive mitochondrial fission.