Fibulin-2 is an extracellular matrix inhibitor of oligodendrocytes relevant to multiple sclerosis.

Impairment of oligodendrocytes and myelin contributes to neurological disorders including multiple sclerosis (MS), stroke and Alzheimer's disease. Regeneration of myelin (remyelination) decreases the vulnerability of demyelinated axons, but this repair process commonly fails with disease progression. A contributor to inefficient remyelination is the altered extracellular matrix (ECM) in lesions that remains to be better defined. We have identified fibulin-2 (FBLN2) as a highly upregulated ECM component in lesions of MS and stroke, and in proteome databases of Alzheimer's disease and traumatic brain injury. Focusing on MS, the inhibitory role of FBLN2 was suggested in the experimental autoimmune encephalomyelitis (EAE) model in which genetic FBLN2 deficiency improved behavioral recovery by promoting the maturation of oligodendrocytes and enhancing remyelination. Mechanistically, when oligodendrocyte progenitors were cultured in differentiation media, FBLN2 impeded their maturation into oligodendrocytes by engaging the Notch pathway, leading to cell death. Adeno-associated virus-deletion of FBLN2 in astrocytes improved oligodendrocyte numbers and functional recovery in EAE and generated new myelin profiles after lysolecithin-induced demyelination. Collectively, our findings implicate FBLN2 as a hitherto unrecognized injury-elevated ECM, and a therapeutic target, that impairs oligodendrocyte maturation and myelin repair.

Impact of Baduanjin exercise combined with rational emotive behavior therapy on sleep and mood in patients with poststroke depression: A randomized controlled trial.

BACKGROUND: Poststroke depression (PSD) is one of the most common stroke complications. It not only leads to a decline in patients' quality of life but also increases the mortality of patients. In this study, the method of combining Chinese traditional exercise Baduanjin with psychotherapy was used to intervene in patients with PSD and to explore the improvement of sleep, mood, and serum levels of brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) levels in patients with PSD by combined treatment. METHODS: A total of 100 patients with PSD who met the inclusion criteria were randomly assigned to Baduanjin group (n = 50) or control group (n = 50). The control group received treatment with escitalopram oxalate and rational emotive behavior therapy, while the experimental group received Baduanjin training in addition to the treatment given to the control group. Changes in sleep efficiency, sleep total time, sleep latency, arousal index, Hamilton Anxiety Rating Scale, Hamilton Depression Scale score, serum BDNF, 5-HT, IL-6 levels, and Modified Barthel Index were measured at baseline, 4 weeks and 8 weeks after intervention, and the results were compared between the 2 groups. RESULTS: Significantly improvements in the sleep efficiency, sleep total time, serum 5-HT, BDNF levels, and Modified Barthel Index score were detected at week 4 in the Baduanjin group than in the control group (P < .05). Additionally, the sleep latency, arousal index, Hamilton Anxiety Rating Scale, Hamilton Depression Scale scores and IL-6 levels in the Baduanjin group were lower than those in the control group (P < .05). After 8 weeks of treatment, the above indexes in the Baduanjin group were further improved compared with the control group (P < .05), and the above indexes of the 2 groups were significantly improved compared with the baseline (P < .001). CONCLUSION: Baduanjin exercise combined with rational emotive behavior therapy effectively improves the mood and sleep status of patients with PSD; It increases the serum levels of 5-HT and BDNF while reducing the level of serum proinflammatory factor IL-6; additionally, the intervention alleviates the degree of neurological impairment, upgrades the ability of daily living, and improves the quality of life.

Designing a smallpox B-cell and T-cell multi-epitope subunit vaccine using a comprehensive immunoinformatics approach.

Smallpox is a highly contagious human disease caused by the variola virus. Although the disease was eliminated in 1979 due to its highly contagious nature and historical pathogenicity, with a mortality rate of up to 30%, this virus is an important candidate for biological weapons. Currently, vaccines are the critical measures to prevent this virus infection and spread. In this study, we designed a peptide vaccine using immunoinformatics tools, which have the potential to activate human immunity against variola virus infection efficiently. The design of peptides derives from vaccine-candidate proteins showing protective potential in vaccinia WR strains. Potential non-toxic and nonallergenic T-cell and B-cell binding and cytokine-inducing epitopes were then screened through a priority prediction using special linkers to connect B-cell epitopes and T-cell epitopes, and an appropriate adjuvant was added to the vaccine construction to enhance the immunogenicity of the peptide vaccine. The 3D structure display, docking, and free energy calculation analysis indicate that the binding affinity between the vaccine peptide and Toll-like receptor 3 is high, and the vaccine receptor complex is highly stable. Notably, the vaccine we designed is obtained from the protective protein of the vaccinia and combined with preventive measures to avoid side effects. This vaccine is highly likely to produce an effective and safe immune response against the variola virus infection in the body. IMPORTANCE: In this work, we designed a vaccine with a cluster of multiple T-cell/B-cell epitopes, which should be effective in inducing systematic immune responses against variola virus infection. Besides, this work also provides a reference in vaccine design for preventing monkeypox virus infection, which is currently prevalent.

The cerebroprotection and prospects of FNDC5/irisin in stroke.

Stroke, the leading cause of disability and cognitive impairment, is also the second leading cause of death worldwide. The drugs with multi-targeted brain cytoprotective effects are increasingly being advocated for the treatment of stroke. Irisin, a newly discovered myokine produced by cleavage of fibronectin type III domain 5, has been shown to regulate glucose metabolism, mitochondrial energy, and fat browning. A large amount of evidence indicated that irisin could exert anti-inflammatory, anti-apoptotic, and antioxidant properties in a variety of diseases such as myocardial infarction, inflammatory bowel disease, lung injury, and kidney or liver disease. Studies have found that irisin is widely distributed in multiple brain regions and also plays an important regulatory role in the central nervous system. The most common cause of a stroke is a sudden blockage of an artery (ischemic stroke), and in some circumstances, a blood vessel rupture can also result in a stroke (hemorrhagic stroke). After a stroke, complicated pathophysiological processes lead to serious brain injury and neurological dysfunction. According to recent investigations, irisin may protect elements of the neurovascular unit by acting on multiple pathological processes in stroke. This review aims to outline the currently recognized effects of irisin on stroke and propose possible directions for future research.

The potentiality of bacteria to drive SARS-CoV-2 mutation.

A recent study published in mBio by Cao et al. revealed the crucial roles of bacteria in benefitting SARS-CoV-2 mutations (B. Cao, X. Wang, W. Yin, Z. Gao, and B. Xia, mBio e3187-23, 2024, https://doi.org/10.1128/mbio.03187-23). Understanding the underlying mechanisms driving the evolution of SARS-CoV-2 is crucial for predicting the future trajectory of the COVID-19 pandemic and developing preventive and treatment strategies. This study provides important insights into the rapid and complex evolution of viruses facilitated by bacterial-virus interactions.

Adjudin protects blood-brain barrier integrity and attenuates neuroinflammation following intracerebral hemorrhage in mice.

Secondary brain injury exacerbates neurological dysfunction and neural cell death following intracerebral hemorrhage (ICH), targeting the pathophysiological mechanism of the secondary brain injury holds promise for improving ICH outcomes. Adjudin, a potential male contraceptive, exhibits neuroprotective effects in brain injury disease models, yet its impact in the ICH model remains unknown. In this study, we investigated the effects of adjudin on brain injury in a mouse ICH model and explored its underlying mechanisms. ICH was induced in male C57BL/6 mice by injecting collagenase into the right striatum. Mice received adjudin treatment (50 mg/kg/day) for 3 days before euthanization and the perihematomal tissues were collected for further analysis. Adjudin significantly reduced hematoma volume and improved neurological function compared with the vehicle group. Western blot showed that Adjudin markedly decreased the expression of MMP-9 and increased the expression of tight junctions (TJs) proteins, Occludin and ZO-1, and adherens junctions (AJs) protein VE-cadherin. Adjudin also decreased the blood-brain barrier (BBB) permeability, as indicated by the reduced albumin and Evans Blue leakage, along with a decrease in brain water content. Immunofluorescence staining revealed that adjudin noticeably reduced the infiltration of neutrophil, activation of microglia/macrophages, and reactive astrogliosis, accompanied by an increase in CD206 positive microglia/macrophages which exhibit phagocytic characteristics. Adjudin concurrently decreased the generation of proinflammatory cytokines, such as TNF-α and IL-1ß. Additionally, adjudin increased the expression of aquaporin 4 (AQP4). Furthermore, adjudin reduced brain cell apoptosis, as evidenced by increased expression of anti-apoptotic protein Bcl-2, and decreased expression of apoptosis related proteins Bax, cleaved caspase-3 and fewer TUNEL positive cells. Our data suggest that adjudin protects against ICH-induced secondary brain injury and may serve as a potential neuroprotective agent for ICH treatment.

Genetically predicted hypotaurine levels mediate the relationship between immune cells and intracerebral hemorrhage.

The evidence supports a strong link between immune cells and intracerebral hemorrhage (ICH). Nonetheless, the specific cause-and-effect associations between immune cells and ICH remain indeterminate. Here, our primary investigation compared immune cell infiltration in the ICH and sham groups using the GSE24265 dataset. Afterward, we extensively examined the relationship between immune cells and ICH by applying a two-sample Mendelian randomization (MR) analysis to identify the particular immune cells that may be associated with the initiation and advancement of ICH. Nevertheless, the specific processes that regulate the cause-and-effect connection between immune cells and ICH remain unknown. In this study, our objective was to investigate the connections between immune cell characteristics and plasma metabolites, as well as the links between plasma components and ICH. Our investigation uncovered that the levels of hypotaurine play a key role in the advancement of ICH, influencing the ratio of switched memory B cells among lymphocytes. Thus, our findings provide novel insights into the potential biological mechanisms underlying immune cell-mediated ICH.

LXR agonism for CNS diseases: promises and challenges.

The unfavorable prognosis of many neurological conditions could be attributed to limited tissue regeneration in central nervous system (CNS) and overwhelming inflammation, while liver X receptor (LXR) may regulate both processes due to its pivotal role in cholesterol metabolism and inflammatory response, and thus receives increasing attentions from neuroscientists and clinicians. Here, we summarize the signal transduction of LXR pathway, discuss the therapeutic potentials of LXR agonists based on preclinical data using different disease models, and analyze the dilemma and possible resolutions for clinical translation to encourage further investigations of LXR related therapies in CNS disorders.

Au-Fe3O4 Janus nanoparticles for imaging-guided near infrared-enhanced ferroptosis therapy in triple negative breast cancer.

Triple-negative breast cancer (TNBC) is insensitive to conventional therapy due to its highly invasive nature resulting in poor therapeutic outcomes. Recent studies have shown multiple genes associated with ferroptosis in TNBC, suggesting an opportunity for ferroptosis-based treatment of TNBC. However, the efficiency of present ferroptosis agents for cancer is greatly restricted due to lack of specificity and low intracellular levels of H2O2 in cancer cells. Herein, we report a nano-theranostic platform consisting of gold (Au)-iron oxide (Fe3O4) Janus nanoparticles (GION@RGD) that effectively enhances the tumor-specific Fenton reaction through utilization of near-infrared (NIR) lasers, resulting in the generation of substantial quantities of toxic hydroxyl radicals (•OH). Specifically, Au nanoparticles (NPs) converted NIR light energy into thermal energy, inducing generation of abundant intracellular H2O2, thereby enhancing the iron-induced Fenton reaction. The generated •OH not only lead to apoptosis of malignant tumor cells but also induce the accumulation of lipid peroxides, causing ferroptosis of tumor cells. After functionalizing with the activity-targeting ligand RGD (Arg-Gly-Asp), precise synergistic treatment of TNBC was achieved in vivo under the guidance of Fe3O4 enhanced T2-weighted magnetic resonance imaging (MRI). This synergistic treatment strategy of NIR-enhanced ferroptosis holds promise for the treatment of TNBC.

Human MARCH1, 2, and 8 block Ebola virus envelope glycoprotein cleavage via targeting furin P domain.

Membrane-associated RING-CH (MARCH) family proteins were recently reported to inhibit viral replication through multiple modes. Previous work showed that human MARCH8 blocked Ebola virus (EBOV) glycoprotein (GP) maturation. Our study here demonstrates that human MARCH1 and MARCH2 share a similar pattern to MARCH8 in restricting EBOV GP-pseudotyped viral infection. Human MARCH1 and MARCH2 retain EBOV GP at the trans-Golgi network, reduce its cell surface display, and impair EBOV GP-pseudotyped virions infectivity. Furthermore, we uncover that the host proprotein convertase furin could interact with human MARCH1/2 and EBOV GP intracellularly. Importantly, the furin P domain is verified to be recognized by MARCH1/2/8, which is critical for their blocking activities. Besides, bovine MARCH2 and murine MARCH1 also impair EBOV GP proteolytic processing. Altogether, our findings confirm that MARCH1/2 proteins of different mammalian origins showed a relatively conserved feature in blocking EBOV GP cleavage, which could provide clues for subsequent MARCHs antiviral studies and may facilitate the development of novel strategies to antagonize enveloped virus infection.

Towards improving the prognosis of stroke through targeting the circadian clock system.

Rhythmicity of the circadian system is a 24-hour period, driven by transcription-translation feedback loops of circadian clock genes. The central circadian pacemaker in mammals is located in the hypothalamic suprachiasmatic nucleus (SCN), which controls peripheral circadian clocks. In general, most physiological processes are regulated by the circadian system, which is modulated by environmental cues such as exposure to light and/or dark, temperature, and the timing of sleep/wake and food intake. The chronic circadian disruption caused by shift work, jetlag, and/or irregular sleep-wake cycles has long-term health consequences. Its dysregulation contributes to the risk of psychiatric disorders, sleep abnormalities, hypothyroidism and hyperthyroidism, cancer, and obesity. A number of neurological conditions may be worsened by changes in the circadian clock via the SCN pacemaker. For stroke, different physiological activities such as sleep/wake cycles are disrupted due to alterations in circadian rhythms. Moreover, the immunological processes that affect the evolution and recovery processes of stroke are regulated by the circadian clock or core-clock genes. Thus, disrupted circadian rhythms may increase the severity and consequences of stroke, while readjustment of circadian clock machinery may accelerate recovery from stroke. In this manuscript, we discuss the relationship between stroke and circadian rhythms, particularly on stroke development and its recovery process. We focus on immunological and/or molecular processes linking stroke and the circadian system and suggest the circadian rhythm as a target for designing effective therapeutic strategies in stroke.

Engineering iron-based nanomaterials for breast cancer therapy associated with ferroptosis.

Ferroptosis has received increasing attention as a novel nonapoptotic programmed death. Recently, iron-based nanomaterials have been extensively exploited for efficient tumor ferroptosis therapy, as they directly release high concentrations of iron and increase intracellular reactive oxygen species levels. Breast cancer is one of the commonest malignant tumors in women; inhibiting breast cancer cell proliferation through activating the ferroptosis pathway could be a potential new target for patient treatment. Here, we briefly introduce the background of ferroptosis and systematically review the current cancer therapeutic strategies based on iron-based ferroptosis inducers. Finally, we summarize the advantages of these various ferroptosis inducers and shed light on future perspectives. This review aims to provide better guidance for the development of iron-based nanomaterial ferroptosis inducers.

Ion Channel Dysregulation Following Intracerebral Hemorrhage.

Injury to the brain after intracerebral hemorrhage (ICH) results from numerous complex cellular mechanisms. At present, effective therapy for ICH is limited and a better understanding of the mechanisms of brain injury is necessary to improve prognosis. There is increasing evidence that ion channel dysregulation occurs at multiple stages in primary and secondary brain injury following ICH. Ion channels such as TWIK-related K+ channel 1, sulfonylurea 1 transient receptor potential melastatin 4 and glutamate-gated channels affect ion homeostasis in ICH. They in turn participate in the formation of brain edema, disruption of the blood-brain barrier, and the generation of neurotoxicity. In this review, we summarize the interaction between ions and ion channels, the effects of ion channel dysregulation, and we discuss some therapeutics based on ion-channel modulation following ICH.

The emerging roles of ac4C acetylation "writer" NAT10 in tumorigenesis: A comprehensive review.

The quick progress of epigenetic study has kindled new hope for treating many cancers. When it comes to RNA epigenetics, the ac4C acetylation modification is showing promise, whereas N-acetyltransferase 10 plays a wide range of biological functions, has a significant impact on cellular life events, and is frequently highly expressed in many malignant tumors. N-acetyltransferase 10 is an acetyltransferase with important biological involvement in cellular processes and lifespan. Because it is highly expressed in many malignant tumors, it is considered a pro-carcinogenic gene. The review aims to introduce NAT10, summarize the effects of ac4C acetylation on tumor growth from multiple angles, and discuss the possible therapeutic targeting of NAT10 and the future directions of ac4C acetylation investigations.

Designing a polyvalent vaccine targeting multiple strains of varicella zoster virus using integrated bioinformatics approaches.

The Varicella Zoster Virus (VZV) presents a global health challenge due to its dual manifestations of chickenpox and shingles. Despite vaccination efforts, incomplete coverage, and waning immunity lead to recurrent infections, especially in aging and immunocompromised individuals. Existing vaccines prevent chickenpox but can trigger the reactivation of shingles. To address these limitations, we propose a polyvalent multiepitope subunit vaccine targeting key envelope glycoproteins of VZV. Through bioinformatics approaches, we selected six glycoproteins that are crucial for viral infection. Epitope mapping led to the identification of cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B cell linear (LBL) epitopes. Incorporating strong immunostimulants, we designed two vaccine constructs, demonstrating high antigenicity, solubility, stability, and compatibility with Toll-like receptors (TLRs). Molecular docking and dynamics simulations underscored the stability and affinity of the vaccine constructs with TLRs. These findings lay the foundation for a comprehensive solution to VZV infections, addressing the challenges of incomplete immunity and shingles reactivation. By employing advanced immunoinformatics and dynamics strategies, we have developed a promising polyvalent multiepitope subunit vaccine candidate, poised to enhance protection against VZV and its associated diseases. Further validation through in vivo studies is crucial to confirm the effectiveness and potential of the vaccine to curb the spread of VZV. This innovative approach not only contributes to VZV control but also offers insights into tailored vaccine design strategies against complex viral pathogens.

Crosstalk Between Matrix Metalloproteinases and Their Inducer EMMPRIN/CD147: a Promising Therapeutic Target for Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is characterized by the disruption of cerebrovascular integrity, resulting in hematoma enlargement, edema formation, and physical damage in the brain parenchyma. Primary ICH also leads to secondary brain injury contributed by oxidative stress, dysregulated immune responses, and proteolysis. In this context, matrix metalloproteinases (MMPs) represent a ubiquitous superfamily of structurally related zinc-dependent endopeptidases capable of degrading all components of the extracellular matrix. They disrupt the blood-brain barrier and promote neuroinflammation. Importantly, several MMP members are upregulated following ICH, and members may have different functions at specific periods in ICH. Hence, the modulation and function of MMPs are more complex than expected. Extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is a transmembrane glycoprotein that induces the production of MMPs. In this review, we systematically discuss the biology and functions of MMPs and EMMPRIN/CD147 in ICH and the complex crosstalk between them.

Prominent elevation of extracellular matrix molecules in intracerebral hemorrhage.

Background: Intracerebral hemorrhage (ICH) is the predominant type of hemorrhagic stroke with high mortality and disability. In other neurological conditions, the deposition of extracellular matrix (ECM) molecules is a prominent obstacle for regenerative processes and an enhancer of neuroinflammation. Whether ECM molecules alter in composition after ICH, and which ECM members may inhibit repair, remain largely unknown in hemorrhagic stroke. Methods: The collagenase-induced ICH mouse model and an autopsied human ICH specimen were investigated for expression of ECM members by immunofluorescence microscopy. Confocal image z-stacks were analyzed with Imaris 3D to assess the association of immune cells and ECM molecules. Sections from a mouse model of multiple sclerosis were used as disease and staining controls. Tissue culture was employed to examine the roles of ECM members on oligodendrocyte precursor cells (OPCs). Results: Among the lectican chondroitin sulfate proteoglycan (CSPG) members, neurocan but not aggrecan, versican-V1 and versican-V2 was prominently expressed in perihematomal tissue and lesion core compared to the contralateral area in murine ICH. Fibrinogen, fibronectin and heparan sulfate proteoglycan (HSPG) were also elevated after murine ICH while thrombospondin and tenascin-C was not. Confocal microscopy with Imaris 3D rendering co-localized neurocan, fibrinogen, fibronectin and HSPG molecules to Iba1+ microglia/macrophages or GFAP+ astrocytes. Marked differentiation from the multiple sclerosis model was observed, the latter with high versican-V1 and negligible neurocan. In culture, purified neurocan inhibited adhesion and process outgrowth of OPCs, which are early steps in myelination in vivo. The prominent expression of neurocan in murine ICH was corroborated in human ICH sections. Conclusion: ICH caused distinct alterations in ECM molecules. Among CSPG members, neurocan was selectively upregulated in both murine and human ICH. In tissue culture, neurocan impeded the properties of oligodendrocyte lineage cells. Alterations to the ECM in ICH may adversely affect reparative outcomes after stroke.

SARS-CoV-2 ORF7a blocked autophagy flux by intervening in the fusion between autophagosome and lysosome to promote viral infection and pathogenesis.

The coronavirus disease 2019 (COVID-19) continues to pose a major threat to public health worldwide. Although many studies have clarified the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection process, the underlying mechanisms of viral invasion and immune evasion were still unclear. This study focused on SARS-CoV-2 ORF7a (open reading frame-7a), one of the essential open reading frames (ORFs) in infection and pathogenesis. First, by analyzing its physical and chemical characteristics, SARS-CoV-2 ORF7a is an unstable hydrophobic transmembrane protein. Then, the ORF7a transmembrane domain three-dimensional crystal structure model was predicted and verified. SARS-CoV-2 ORF7a localized in the endoplasmic reticulum and participated in the autophagy-lysosome pathway via interacting with p62. In addition, we elucidated the underlying molecular mechanisms by which ORF7a intercepted autophagic flux, promoted double membrane vesicle formation, and evaded host autophagy-lysosome degradation and antiviral innate immunity. This study demonstrated that ORF7a could be a therapeutic target, and Glecaprevir may be a potential drug against SARS-CoV-2 by targeting ORF7a. A comprehensive understanding of ORF7a's functions may contribute to developing novel therapies and clinical drugs against COVID-19.

Anti-oxidant effects of cannabidiol relevant to intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a subtype of stroke with a high mortality rate. Oxidative stress cascades play an important role in brain injury after ICH. Cannabidiol, a major non-psychotropic phytocannabinoids, has drawn increasing interest in recent years as a potential therapeutic intervention for various neuropsychiatric disorders. Here we provide a comprehensive review of the potential therapeutic effects of cannabidiol in countering oxidative stress resulting from ICH. The review elaborates on the various sources of oxidative stress post-ICH, including mitochondrial dysfunction, excitotoxicity, iron toxicity, inflammation, and also highlights cannabidiol's ability to inhibit ROS/RNS generation from these sources. The article also delves into cannabidiol's role in promoting ROS/RNS scavenging through the Nrf2/ARE pathway, detailing both extranuclear and intranuclear regulatory mechanisms. Overall, the review underscores cannabidiol's promising antioxidant effects in the context of ICH and suggests its potential as a therapeutic option.

Omarigliptin inhibits brain cell ferroptosis after intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a disastrous disease without effective treatment. An extensive body of evidence indicate that neuronal ferroptosis is a key contributor to neurological disfunctions after ICH. Omarigliptin, also known as MK3102, is an anti-diabetic drug that inhibits dipeptidyl peptidase (DPP4). Recently, MK3102 is reported to exhibit anti-ferroptosis and anti-oxidative effects in different pathological conditions. However, the anti-ferroptosis ability of MK3102 in ICH injury is unknown. Hemin was administrated to model ICH injury in cultured primary cortical neurons, and collagenase VII was used to induce ICH in C57BL/6 mice. MK3102 was administered after ICH. Cell Counting Kit-8 (CCK-8) was applied to detect cell viability. Neurological functions were assessed through the Focal deficits neurological scores and corner test. HE and TUNEL staining was applied to evaluate brain damage areas and cell death, respectively. Ferroptosis was evaluated in cultured neurons by fluorescent probe DCFH-DA, FerroOrange, Liperfluo and immunofluorescence of GPX4, AIFM2 and FACL4. Perls staining was performed to visualize Fe3+ deposition. Ferroptosis-related proteins in mouse brain were measured by immunohistochemistry and western blotting. MK3102 reduced the neurotoxicity of hemin in cultured primary cortical neurons. It improved neurological functions associated with a decrease in the number of dead neurons and the area of brain damage after ICH in mice. Moreover, MK3102 prominently upregulated glucagon-like peptide-1 receptor (GLP-1R) levels after ICH. In addition, the elevation of iron content, lipid peroxidation and FACL4 after ICH; and reduction of GPX4 and AIFM2; were mitigated by MK3102 in vitro and in vivo. The neuroprotective effect of MK3102 may be related to anti-ferroptosis by regulating GLP-1R after ICH injury.