Neuron-targeted liposomal coenzyme Q10 attenuates neuronal ferroptosis after subarachnoid hemorrhage by activating the ferroptosis suppressor protein 1/coenzyme Q10 system.

Subarachnoid hemorrhage (SAH) is primarily attributed to the rupture of intracranial aneurysms and is associated with a high incidence of disability and mortality. SAH disrupts the blood‒brain barrier, leading to the release of iron ions from blood within the subarachnoid space, subsequently inducing neuronal ferroptosis. A recently discovered protein, known as ferroptosis suppressor protein 1 (FSP1), exerts anti-ferroptotic effects by facilitating the conversion of oxidative coenzyme Q 10 (CoQ10) to its reduced form, which effectively scavenges reactive oxygen radicals and mitigates iron-induced ferroptosis. In our investigation, we observed an increase in FSP1 levels following SAH. However, the depletion of CoQ10 caused by SAH hindered the biological function of FSP1. Therefore, we created neuron-targeted liposomal CoQ10 by introducing the neuron-targeting peptide Tet1 onto the surface of liposomal CoQ10. Our objective was to determine whether this formulation could activate the FSP1 system and subsequently inhibit neuronal ferroptosis. Our findings revealed that neuron-targeted liposomal CoQ10 effectively localized to neurons at the lesion site after SAH. Furthermore, it facilitated the upregulation of FSP1, reduced the accumulation of malondialdehyde and reactive oxygen species, inhibited neuronal ferroptosis, and exerted neuroprotective effects both in vitro and in vivo. Our study provides evidence that supplementation with CoQ10 can effectively activate the FSP1 system. Additionally, we developed a neuron-targeted liposomal CoQ10 formulation that can be selectively delivered to neurons at the site of SAH. This innovative approach represents a promising therapeutic strategy for neuronal ferroptosis following SAH. STATEMENT OF SIGNIFICANCE: Subarachnoid hemorrhage (SAH) is primarily attributed to the rupture of intracranial aneurysms and is associated with a high incidence of disability and mortality. Ferroptosis suppressor protein 1 (FSP1), exerts anti-ferroptotic effects by facilitating the conversion of oxidative coenzyme Q 10 (CoQ10) to its reduced form, which effectively scavenges reactive oxygen radicals and mitigates iron-induced ferroptosis. In our investigation, we observed an increase in FSP1 levels following SAH. However, the depletion of CoQ10 caused by SAH hindered the biological function of FSP1. Therefore, we created neuron-targeted liposomal CoQ10. We find that it effectively localized to neurons at the lesion site after SAH and activated the FSP1/CoQ10 system. This innovative approach represents a promising therapeutic strategy for neuronal ferroptosis following SAH and other central nervous system diseases characterized by disruption of the blood-brain barrier.

Gender potentially affects early postoperative hyponatremia in pituitary adenoma: XGBoost-based predictive modeling.

Purpose: The occurrence of hyponatremia is a prevalent complication following transnasal transsphenoidal surgery for pituitary adenoma surgery, which adversely affects patient prognosis, hospitalization duration, and rehospitalization risk. The primary objective of this study is to strengthen the correlation between clinical factors associated with pituitary adenoma and postoperative hyponatremia. Additionally, the study aims to develop a predictive model for postoperative hyponatremia in patients with pituitary adenoma, with the ultimate goal of establishing a basis for reducing the occurrence of postoperative hyponatremia following surgical interventions. Methods: The chi-square test or Fisher test was employed for nominal data, while the t-test or Mann-Whitney test was utilized for continuous data analysis. In cases where the data exhibited statistical differences, binary logistic analysis was conducted to examine the risk and protective factors associated with postoperative hyponatremia. XGBoost was employed to construct predictive models for hyponatremia in this study. The patients were partitioned into training and test sets, and the most suitable parameters were determined through five-fold cross-validation and subsequently utilized for training on the training set. The discriminatory capability was assessed on the internal validation set. Results and conclusions: Out of the total 280 patients included in this investigation, 82 patients experienced early postoperative hyponatremia. Among these individuals, male gender (P = 0.02, odds ratio = 1.98) was identified as a risk factor for early postoperative hyponatremia, while preoperative chloride levels (P = 0.021, odds ratio = 0.866) and surgery time (P = 0.039, odds ratio = 0.990) were identified as protective factors against postoperative hyponatremia. The XGBoost model exhibited a sensitivity of 94.2%, a specificity of 61.5%, a positive predictive value of 51.6%, a negative predictive value of 96%, and identified male gender, preoperative sodium, and preoperative cortisol as the most significant predictors. Our findings indicate that gender may have influence in the development of early postoperative hyponatremia in patients with pituitary adenomas.

Hydrogen exerts neuroprotective effects after subarachnoid hemorrhage by attenuating neuronal ferroptosis and inhibiting neuroinflammation.

OBJECTIVE: Spontaneous subarachnoid hemorrhage (SAH), the third most common stroke subtype, is associated with high mortality and disability rates. Therefore, finding effective therapies to improve neurological function after SAH is critical. The objective of this study was to investigate the potential neuroprotective effects of hydrogen in the context of SAH, specifically, by examining its role in attenuating neuronal ferroptosis and inhibiting neuroinflammation, which are exacerbated by excess iron ions after SAH. METHODS: Mice were exposed to chambers containing 3% hydrogen, and cells were cultured in incubators containing 60% hydrogen. Neurological function in mice was assessed using behavioral scores. Protein changes were detected using western blotting. Inflammatory factors were detected using enzyme linked immunosorbent assay. Probes, electron microscopy, and related kits were employed to detect oxidative stress and ferroptosis. RESULTS: Hydrogen improved the motor function, sensory function, and cognitive ability of mice after SAH. Additionally, hydrogen facilitated Nuclear factor erythroid 2 -related factor 2 activation, upregulated Glutathione peroxidase 4, and inhibited Toll-like receptor 4, resulting in downregulation of inflammatory responses, attenuation of oxidative stress after SAH, and inhibition of neuronal ferroptosis. CONCLUSION: Hydrogen exerts neuroprotective effects by inhibiting neuronal ferroptosis and attenuating neuroinflammation after SAH.

Novel perfluorocarbon-based oxygenation therapy alleviates Post-SAH hypoxic brain injury by inhibiting HIF-1α.

In comparison to other stroke types, subarachnoid hemorrhage (SAH) is characterized by an early age of onset and often results in poor prognosis. The inadequate blood flow at the site of the lesion leads to localized oxygen deprivation, increased level of hypoxia-inducible factor-1α (HIF-1α), and triggers inflammatory responses and oxidative stress, ultimately causing hypoxic brain damage. Despite the potential benefits of oxygen (O2) administration, there is currently a lack of efficient focal site O2 delivery following SAH. Conventional clinical O2 supply methods, such as transnasal oxygenation and hyperbaric oxygen therapy, do not show the ideal therapeutic effect in severe SAH patients. The perfluorocarbon oxygen carrier (PFOC) demonstrates efficacy in transporting O2 and responding to elevated levels of CO2 at the lesion site. Through cellular experiments, we determined that PFOC oxygenation serves as an effective therapeutic approach in inhibiting hypoxia. Furthermore, our animal experiments showed that PFOC oxygenation outperforms O2 breathing, leading to microglia phenotypic switching and the suppression of inflammatory response via the inhibition of HIF-1α. Therefore, as a new type of O2 therapy after SAH, PFOC oxygenation can effectively reduce hypoxic brain injury and improve neurological function.

Menaquinone-4 attenuates ferroptosis by upregulating DHODH through activation of SIRT1 after subarachnoid hemorrhage.

BACKGROUND: Menaquinone-4(MK-4), the isoform of vitamin K2 in the brain, exerts neuroprotective effects against a variety of central nervous system disorders. This study aimed to demonstrate the anti-ferroptosis effects of MK-4 in neurons after SAH. METHODS: A subarachnoid hemorrhage (SAH) model was prepared by endovascular perforation in mice. In vitro hemoglobin stimulation of primary cortical neurons mimicked SAH. MK-4, Brequinar (BQR, DHODH inhibitor), and Selisistat (SEL, SIRT1 inhibitor) were administered, respectively. Subsequently, WB, immunofluorescence was used to determine protein expression and localization, and transmission electron microscopy was used to observe neuronal mitochondrial structure while other indicators of ferroptosis were measured. RESULTS: MK-4 treatment significantly upregulated the protein levels of DHODH; decreased GSH, PTGS2, NOX1, ROS, and restored mitochondrial membrane potential. Meanwhile, MK-4 upregulated the expression of SIRT1 and promoted its entry into the nucleus. BQR or SEL partially abolished the protective effect of MK-4 on, neurologic function, and ferroptosis. CONCLUSIONS: Taken together, our results suggest that MK-4 attenuates ferroptosis after SAH by upregulating DHODH through the activation of SIRT1.

P38-DAPK1 axis regulated LC3-associated phagocytosis (LAP) of microglia in an in vitro subarachnoid hemorrhage model.

BACKGROUND: The phagocytosis and homeostasis of microglia play an important role in promoting blood clearance and improving prognosis after subarachnoid hemorrhage (SAH). LC3-assocaited phagocytosis (LAP) contributes to the microglial phagocytosis and homeostasis via autophagy-related components. With RNA-seq sequencing, we found potential signal pathways and genes which were important for the LAP of microglia. METHODS: We used an in vitro model of oxyhemoglobin exposure as SAH model in the study. RNA-seq sequencing was performed to seek critical signal pathways and genes in regulating LAP. Bioparticles were used to access the phagocytic ability of microglia. Western blot (WB), immunoprecipitation, quantitative polymerase chain reaction (qPCR) and immunofluorescence were performed to detect the expression change of LAP-related components and investigate the potential mechanisms. RESULTS: In vitro SAH model, there were increased inflammation and decreased phagocytosis in microglia. At the same time, we found that the LAP of microglia was inhibited in all stages. RNA-seq sequencing revealed the importance of P38 MAPK signal pathway and DAPK1 in regulating microglial LAP. P38 was found to regulate the expression of DAPK1, and P38-DAPK1 axis was identified to regulate the LAP and homeostasis of microglia after SAH. Finally, we found that P38-DAPK1 axis regulated expression of BECN1, which indicated the potential mechanism of P38-DAPK1 axis regulating microglial LAP. CONCLUSION: P38-DAPK1 axis regulated the LAP of microglia via BECN1, affecting the phagocytosis and homeostasis of microglia in vitro SAH model. Video Abstract.

Dihydromyricetin confers cerebroprotection against subarachnoid hemorrhage via the Nrf2-dependent Prx2 signaling cascade.

BACKGROUND: Several clinical and experimental studies have shown that therapeutic strategies targeting oxidative damage are beneficial for subarachnoid hemorrhage (SAH). A brain-permeable flavonoid, dihydromyricetin (DHM), can modulate redox/oxidative stress and has cerebroprotective effects in several neurological disorders. The effects of DHM on post-SAH early brain injury (EBI) and the underlying mechanism have yet to be clarified. PURPOSE: This work investigated a potential role for DHM in SAH, together with the underlying mechanisms. METHODS: Cerebroprotection by DHM was studied using a SAH rat model and primary cortical neurons. Atorvastatin (Ato) was a positive control drug in this investigation. The effects of DHM on behavior after SAH were evaluated by performing the neurological rotarod and Morris water maze tests, as well as by examining its effects on brain morphology and on the molecular and functional phenotypes of primary cortical neurons using dichlorodihydrofluorescein diacetate (DCFH-DA), immunofluorescent staining, biochemical analysis, and Western blot. RESULTS: DHM was found to significantly reduce the amount of reactive oxygen species (ROS), suppress mitochondrial disruption, and increase intrinsic antioxidant enzymatic activity following SAH. DHM also significantly reduced neuronal apoptosis in SAH rats and improved short- and long-term neurological functions. DHM induced significant increases in peroxiredoxin 2 (Prx2) and nuclear factor erythroid 2-related factor 2 (Nrf2) expression, while decreasing phosphorylation of p38 and apoptotic signal-regulated kinase 1 (ASK1). In contrast, reduction of Prx2 expression using small interfering ribonucleic acid or by inhibiting Nrf2 with ML385 attenuated the neuroprotective effect of DHM against SAH. Moreover, DHM dose-dependently inhibited oxidative damage, decreased neuronal apoptosis, and increased the viability of primary cultured neurons in vitro. These positive effects were associated with Nrf2 activation and stimulation of Prx2 signaling, whereas ML385 attenuated the beneficial effects. CONCLUSION: These results reveal that DHM protects against SAH primarily by modulating the Prx2 signaling cascade through the Nrf2-dependent pathway. Hence, DHM could be a valuable therapeutic candidate for SAH treatment.

Hydrogen inhalation therapy regulates lactic acid metabolism following subarachnoid hemorrhage through the HIF-1α pathway.

The neuroprotective effects of hydrogen have been demonstrated, but the mechanism is still poorly understood. In a clinical trial of inhaled hydrogen in patients with subarachnoid hemorrhage (SAH), we found that hydrogen reduced the accumulation of lactic acid in the nervous system. There are no studies demonstrating the regulatory effect of hydrogen on lactate and in this study we hope to further clarify the mechanism by which hydrogen regulates lactate metabolism. In cell experiments, PCR and Western Blot showed that HIF-1α was the target related to lactic acid metabolism that changed the most before and after hydrogen intervention. HIF-1α levels were suppressed by hydrogen intervention treatment. Activation of HIF-1α inhibited the lactic acid-lowering effect of hydrogen. We have also demonstrated the lactic acid-lowering effect of hydrogen in animal studies. Our work clarifies that hydrogen can regulate lactate metabolism via the HIF-1αpathway, providing new insights into the neuroprotective mechanisms of hydrogen.

Peroxiredoxin 2 Is a Potential Objective Indicator for Severity and the Clinical Status of Subarachnoid Hemorrhage Patients.

Purpose: We have demonstrated that peroxiredoxin 2 (Prx2) released from lytic erythrocytes and damaged neurons into the subarachnoid space could activate microglia and then result in neuronal apoptosis. In this study, we tested the possibility of using Prx2 as an objective indicator for severity of the subarachnoid hemorrhage (SAH) and the clinical status of the patient. Materials and Methods: SAH patients were prospectively enrolled and followed up for 3 months. Cerebrospinal fluid (CSF) and blood samples were collected 0-3 and 5-7 days after SAH onset. The levels of Prx2 in the CSF and the blood were measured by an enzyme-linked immunosorbent assay (ELISA). We used Spearman's rank coefficient to assess the correlation between Prx2 and the clinical scores. Receiver operating characteristic (ROC) curves were used for Prx2 levels to predict the outcome of SAH by calculating the area under the curve (AUC). Unpaired Student's t-test was used to analyze the differences in continuous variables across cohorts. Results: Prx2 levels in the CSF increased after onset while those in the blood decreased. Existing data showed that Prx2 levels within 3 days in the CSF after SAH were positively correlated with the Hunt-Hess score (R = 0.761, P < 0.001). Patients with CVS had higher levels of Prx2 in their CSF within 5-7 days after onset. Prx2 levels in the CSF within 5-7 days can be used as a predictor of prognosis. The ratio of Prx2 in the CSF and the blood within 3 days of onset was positively correlated with the Hunt-Hess score and negatively correlated with Glasgow Outcome Scale (GOS; R = -0.605, P < 0.05). Conclusion: We found that the levels of Prx2 in the CSF and the ratio of Prx2 in the CSF and the blood within 3 days of onset can be used as a biomarker to detect the severity of the disease and the clinical status of the patient.

Comparison of the preoperative diagnostic accuracy of BIPSS versus MRI for Cushing disease: a single-centre experience.

BACKGROUND: Cushing disease (CD) arises due to a pituitary corticotroph adenoma, which is the most common cause of Cushing syndrome (CS). Bilateral inferior petrosal sinus sampling (BIPSS) is a safe method for differentiating CD from ectopic adrenocorticotropic hormone (ACTH)-dependent CS. Enhanced high-resolution magnetic resonance imaging (MRI) can localize tiny pituitary lesions. The aim of this study was to compare the preoperative diagnostic accuracy of BIPSS versus MRI for CD in CS patients. We performed a retrospective study of patients who underwent BIPSS and MRI between 2017 and 2021. Low- and high-dose dexamethasone suppression tests were performed. Blood samples were collected simultaneously from the right and left catheter and femoral vein before and after desmopressin stimulation. MRI images were obtained, and endoscopic endonasal transsphenoidal surgery (EETS) was performed in confirmed CD patients. Dominant sides of ACTH secretion during BIPSS and MRI were compared with surgical findings. RESULTS: Twenty-nine patients underwent BIPSS and MRI. CD was diagnosed in 28 patients, 27 of whom received EETS. Localizations of microadenomas by MRI and BIPSS agreed with the EETS findings in 96% and 93% of the cases, respectively. BIPSS and EETS were successfully performed on all patients. CONCLUSION: BIPSS was the most accurate method (gold standard) for establishing a preoperative diagnosis of pituitary-dependent CD and was more sensitive than MRI in diagnosing microadenoma. High-resolution MRI with enhancement had an advantage over BIPSS in microadenoma lateralization diagnostics. The combined use of MRI and BIPSS could improve the preoperative diagnosis accuracy in ACTH-dependent CS patients.

Predictive Value of Leucine-Rich Alpha-2 Glycoprotein 1 in Cerebrospinal Fluid for the Prognosis of Aneurysmal Subarachnoid Hemorrhage: A Prospective Study.

OBJECTIVE: To determine whether leucine-rich alpha-2 glycoprotein 1 (LRG1) is a potential prognostic and severity biomarker in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: This observational and prospective study included 44 patients with aSAH from Nanjing Drum Tower Hospital from June to December 2020. Concentrations of LRG1 in the cerebrospinal fluid (CSF) were determined by enzyme-linked immunosorbent assay within 24 hours after aSAH. We further determined the relationship of CSF LRG1 levels with disease severity and prognosis 3 months after aSAH. RESULTS: Higher CSF LRG1 levels were associated with a higher Hunt-Hess grade (P < 0.05). Using univariate analysis, poor outcomes at 3 months were associated with higher World Federation of Neurological Surgeons scale grade, higher Hunt-Hess grade, higher CSF LRG1 levels, and higher Fisher grade. Logistic regression analysis revealed a significant impact of LRG1 on poor outcomes as well as after adjustment for confounding factors. CONCLUSIONS: These findings suggest an increase in CSF LRG1 levels in patients with aSAH, which may serve as a potential biomarker of unfavorable prognosis and disease severity.

Continued P2X7 activation leads to mitochondrial fission and compromising microglial phagocytosis after subarachnoid haemorrhage.

Subarachnoid haemorrhage (SAH) has a high rate of disability and mortality. Extremely damaging molecules, including adenosine triphosphate (ATP), are released from extravasated red blood cells and nerve cells, which activate microglia and induce sterile tissue injury and organ dysfunction. P2X purinoceptor 7 (P2X7) is one of the most important purine receptors on the microglial surface and is involved in the proinflammatory activation of microglia. While P2X7 can also affect microglial phagocytosis, the mechanism is not clear. Here, we demonstrated that microglial phagocytosis is progressively impaired under continued BzATP exposure and P2X7 activation. Furthermore, we found that P2X7 activation leads to increased intracellular Ca2+ levels and activates Calcineurin, which dephosphorylates dynamin-related protein 1 (DRP1) S637. The dephosphorylation of DRP1 at S637 leads to increased mitochondrial fission and decreased mitochondrial function, which may be responsible for the decreased microglial phagocytosis. Finally, we pharmacologically inhibited P2X7 activation in mice, which resulted in rescue of mitochondrial function and decreased microglial proliferation, but improved phagocytosis after SAH. Our study confirmed that P2X7 activation after SAH leads to the impairment of microglial phagocytosis through mitochondrial fission and verified that P2X7 inhibition restores microglial phagocytosis both in vitro and in vivo.

Long-Term Elevated Siglec-10 in Cerebral Spinal Fluid Heralds Better Prognosis for Patients with Aneurysmal Subarachnoid Hemorrhage.

The presence of aneurysmal subarachnoid hemorrhage (aSAH) is usually accompanied by excessive inflammatory response leading to damage of the central nervous system, and the sialic acid-binding Ig-like lectin 10 (Siglec-10) is a recognized factor being able to modify the inflammatory reaction. To investigate the potential role of Siglec-10 in aSAH, we collected the cerebrospinal fluid (CSF) of control (n = 11) and aSAH (n = 14) patients at separate times and measured the Siglec-10 concentration utilizing the enzyme-linked immunosorbent assay (ELISA) and evaluated the alterations of GOS and GCS during the disease process. In accordance with the STROBE statement, results showed that Siglec-10 in CSF rose quickly in response aSAH attack and then fell back to a slightly higher range above baseline, while it remained at relative high concentration and last longer in several severely injured patients. In general, higher Siglec-10 expression over a longer period usually indicated a better clinical prognosis. This prospective cohort study suggested that Siglec-10 could possibly be used as a biomarker for predicting prognosis of aSAH due to its ability to balance aSAH-induced nonsterile inflammation. Additionally, these findings might provide novel therapeutic perspectives for aSAH and other inflammation-related diseases.

Alpha-Ketoglutarate Alleviates Neuronal Apoptosis Induced by Central Insulin Resistance through Inhibiting S6K1 Phosphorylation after Subarachnoid Hemorrhage.

Neuronal apoptosis after subarachnoid hemorrhage (SAH) is believed to play an important role in early brain injury after SAH. The energy metabolism of neuron is closely related to its survival. The transient hyperglycemia caused by insulin resistance (IR) after SAH seriously affects the prognosis of patients. However, the specific mechanisms of IR after SAH are still not clear. Studies have shown that α-KG takes part in the regulation of IR and cell apoptosis. In this study, we aim to investigate whether α-KG can reduce IR after SAH, improve the disorder of neuronal glucose metabolism, alleviate neuronal apoptosis, and ultimately play a neuroprotective role in SAH-induced EBI. We first measured α-KG levels in the cerebrospinal fluid (CSF) of patients with SAH. Then, we established a SAH model through hemoglobin (Hb) stimulation with HT22 cells for further mechanism research. Furthermore, an in vivo SAH model in mice was established by endovascular perforation. Our results showed that α-KG levels in CSF significantly increased in SAH patients and could be used as a potential prognostic biomarker. In in vitro model of SAH, we found that α-KG not only inhibited IR-induced reduction of glucose uptake in neurons after SAH but also alleviated SAH-induced neuronal apoptosis. Mechanistically, we found that α-KG inhibits neuronal IR by inhibiting S6K1 activation after SAH. Moreover, neuronal apoptosis significantly increased when glucose uptake was reduced. Furthermore, our results demonstrated that α-KG could also alleviate neuronal apoptosis in vivo SAH model. In conclusion, our study suggests that α-KG alleviates apoptosis by inhibiting IR induced by S6K1 activation after SAH.

Astrocytic CD24 Protects Neuron from Recombinant High-Mobility Group Box 1 Protein(rHMGB1)-Elicited Neuronal Injury.

Endogenous host-derived molecules named damage-associated molecular patterns (DAMPs) can induce excessive non-sterile inflammatory responses on recognition of specific membrane-tethered receptors. Here in this study, we aimed to explore the role of DAMP molecule HMGB1 in astrocyte-mediated sterile neuroinflammation and the resultant influences on neurons. In vitro cultured astrocytes were challenged with rHMGB1 and then harvested at 6 h, 12 h, 24 h, 36 h, and 48 h, respectively. The astrocytic CD24 expression was determined by quantitative real-time polymerase chain reaction (qPCR), Western blot analysis and immunofluorescence, nuclear factor kappa B (NF-κB) binding activity was detected by electrophoretic mobility shift assay (EMSA), and the proinflammatory factors, tumor necrosis factor-α (TNF-α), and interleukin 1ß (IL-1ß), were measured by qPCR. The neuronal morphology was assessed with phase-contrast microscopy. The results showed that astrocytic mRNA and protein CD24 expression began to rise at 24 h, peaked at 36 h, and remained elevated at 48 h after rHMGB1 stimulation, accompanied with enhanced NF-κB binding activity and augmented expression of TNF-α and IL-1ß. Furthermore, rHMGB1 caused cocultured neuron damage and was aggregated upon CD24 knockdown. Taken together, these novel findings suggested that rHMGB1 could promote astrocytic CD24 expression, the inhibition of which could aggregate neuronal damage.

Efficacy of Liquid Embolic Agent Treatment in Hemorrhagic Peripheral Intracranial Aneurysms: A Single-Center Experience.

Objective: To evaluate the efficacy of liquid embolization agents for treating various hemorrhagic peripheral intracranial aneurysms. Methods: We retrospectively analyzed 38 patients who suffered from hemorrhagic peripheral intracranial aneurysms and were treated with liquid embolization agents. We used the modified Rankin scale for follow-up at 6 months postoperatively, and digital subtraction angiography follow-up was performed 6 months postoperatively. Results: Of the 38 patients (ten of simple peripheral intracranial aneurysms, six of Moyamoya disease (MMD), and 22 of arteriovenous malformation (AVM)), posterior circulation accounted for the most significant proportion (57.9%), followed by anterior circulation (21.1%) and intranidal aneurysms (21.1%). Intraoperative hemorrhage occurred in four cases, postoperative cerebral infarction occurred in four cases, two patients encountered microcatheter retention, and intraoperative thrombosis took place in the basilar artery of a patient with an arteriovenous malformation. A postoperative hemorrhage occurred in only one patient. At 6-month follow-up, 84.2% of patients had good prognosis outcomes, and 13.5% had poor outcomes. Conclusion: Liquid embolization agents are effective for hemorrhagic peripheral intracranial aneurysms; however, safety depends on the subtypes. For peripheral hemorrhagic aneurysms in MMD, the vessel architecture must be carefully evaluated before embolization.