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8 recordsLinked to original sources
PubMed2026

Unveiling m7G modification patterns and causal drivers governing intracranial aneurysm rupture risk through multi-omics validation and m7G-MeRIP-seq profiling.

Intracranial aneurysm (IA) rupture causes severe brain hemorrhage with high mortality, yet its molecular drivers remain unclear and better risk prediction is urgently needed. Using transcriptomics, single-cell analysis, and genetic data, we investigated the role of N7-methylguanosine (m7G) RNA modification in IA. We identified distinct m7G modification patterns, validated their methylation features in patient samples, and incorporated these patterns into a machine learning-based rupture prediction model. The presence and characteristics of m7G patterns significantly improved model performance, achieving high predictive accuracy across three independent cohorts (AUC 0.91-0.95). Genetic analyses further identified three causal m7G-related genes (NSUN2, IFIT5, SNUPN), and laboratory experiments confirmed their altered expression and methylation in ruptured aneurysms. Overall, our findings demonstrate that m7G modifications play a key role in IA rupture. The validated prediction model offers strong clinical potential for rupture risk assessment, and the identified genes represent promising therapeutic targets.

Humans↗
PubMed2026

Multi-Omics Genome-Wide to Explore the Formation and Development Targets for Intracranial Aneurysms.

Intracranial aneurysms (IAs) represent a significant and potentially life-threatening category of disease, and there is currently a lack of effective treatment options aimed at preventing the progression of the disease. Accordingly, this study is dedicated to exploring and identifying effective drug targets that can help in the prevention of both the formation and rupture of IAs, along with a detailed examination of the underlying potential mechanisms involved in these processes. The data related to IAs for this research was obtained from the ISGC Biobank and UK Biobank. Then, we investigated the possible biological functions and unintended consequences of targeting the specific genes that were highlighted in IAs by using mediation analysis, virtual knockout experiments, and PW-MR studies. A total of 5 unique potential drug targets for IAs (FKTN, MAP3K1, PSMA4, SLC22A4, ADAM17), 4 unique potential drug targets for SAH (PSMA4, ADAM17, GPR160, SLC22A4), and 2 unique potential drug targets for UIA (SLC22A4, PRCP) were identified across brain or blood samples. Among the various candidates identified, SLC22A4 has emerged as a promising potential drug target, showing significant expression levels in both blood and brain tissues. Additionally, phenome-wide MR of SLC22A4 across 32 selected phenotypes did not identify statistically significant adverse associations after FDR correction. Virtual knockout (KO) experiments on SLC22A4 revealed that SLC22A4 KO disrupted 81 genes, all of which are involved in IAs-related pathways. Besides, we recognized BRD-K85337334 as potential candidates for targeting SLC22A4. This research indicates that an increase in SLC22A4 gene expression within the blood or brain is directly linked to a heightened risk of IAs rupture, which will aid in prioritizing the development of drugs for IAs.

Humans↗
PubMed2026

Preliminary Exploration on Melatonin-Mediated Protective Effects in Intracranial Aneurysms: Transcriptomic, Proteomic, and Metabolomic Profiling of Cerebral Vascular Tissues Combined with in vivo Animal Experiments.

BACKGROUND: Intracranial aneurysm (IA) is a life-threatening cerebrovascular disease with unclear molecular mechanisms and limited drug treatment. Our previous research has shown that melatonin (MLT) has potential protective effects in IA, but its mechanism remains unclear. The purpose of this study is to explore the pathological mechanism of IA and the therapeutic mechanism of MLT by integrating transcriptomic, proteomic and metabolomic analyses. METHODS: In this study, mouse models of IA were successfully established by combining elastase injection with angiotensin II infusion. C57BL/6 mice were divided into control, IA model, IA model+MLT, and IA model+nimodipine groups. The pathological conditions were evaluated by hematoxylin-eosin (HE) staining, TUNEL staining, and scanning electron microscopy. Transcriptomic (n=3 for each group), proteomic (n=3 for each group), and metabolomic (n=6 for each group) analyses were performed based on cerebral vascular tissue samples. The screening thresholds for differentially expressed genes and differentially expressed proteins were P <0.05 and fold change >1.5 and fold change <0.667. The screening criteria for differential metabolites were variable importance for the projection (VIP)> 1.0, fold change >1.2 and fold change <0.833, and P <0.05. RESULTS: MLT alleviated brain tissue damage, vascular endothelial damage, structural disruption, and apoptosis in IA mice. Transcriptomic, proteomic and metabolomic analyses identified numerous differential molecules. Functional annotation revealed that these molecules may be involved in biological pathways and processes such as immune inflammation, vascular remodeling, extracellular matrix remodeling, neuropeptide activity, oxidative stress and metabolic pathways, thereby regulating the occurrence and development of IA or mediating the therapeutic effects of MLT. Furthermore, transcriptomic and proteomic analyses also suggest that there may be extensive post-transcriptional, translational and post-translational regulatory events in the progression of IA and the therapeutic effects of MLT. Integrated transcriptomic and proteomic analyses suggest that Npy may be a key molecule in regulating IA progression and mediating MLT therapeutic effects, and its potential value is further supported by our immunohistochemical validation results. CONCLUSION: Multi-omics integrative analysis preliminarily revealed that the potential mechanisms of MLT may involve the regulation of inflammatory response, vascular remodeling, extracellular matrix remodeling, neuropeptide activity, oxidative stress, metabolic pathways, and post-transcriptional/translational regulation.

Animals↗
PubMed2026

Short-term safety of dual versus single antiplatelet therapy in flow diversion for distal intracranial aneurysms: results from the DART trial.

BACKGROUND AND PURPOSE: Flow diverters (FDs) have become one of the primary treatments for intracranial aneurysms (IAs). However, their use in distal IA has been associated with higher complication rates compared with other techniques. The development of coated FDs, in combination with novel antiplatelet regimens, offers promising strategies to improve the safety profile of FDs in this context. This trial aimed to compare mono antiplatelet therapy (MAPT) using prasugrel versus dual antiplatelet therapy (DAPT) with aspirin and prasugrel for the treatment of distal IA using the p48 MW HPC FD (WallabyPhenox). METHODS: This was a multicenter, prospective, parallel-group, single-blind, non-inferiority randomized trial. Between February 2021 and February 2025, 140 patients were enrolled. After excluding 11 patients, 129 were included in the final analysis. The primary endpoint was the absence of new neurological deficits, defined as no shift in the modified Rankin Scale (mRS) score. The secondary endpoint was the incidence of any stroke. RESULTS: At the 30-day follow-up, 66 patients (98.5%) in the MAPT group and 59 patients (95.2%) in the DAPT group showed no new neurological deficits. With a predefined non-inferiority margin of 5%, the difference of 3.35% confirmed the non-inferiority of MAPT compared with DAPT (p=0.002). The incidence of any stroke was 4/67 (5.9%) in the MAPT group and 6/62 (9.6%) in the DAPT group (p=0.431). CONCLUSION: Prasugrel monotherapy for the treatment of distal IAs using the p48 MW HPC was non-inferior to DAPT within the first 30 days following treatment. CLINICAL TRIAL REGISTRATION: https://ensaiosclinicos.gov.br/rg/RBR-3q9zb73. UTN code: U1111-1290-2489. Research Ethics Committee of the Hospital das Cl&#xed;nicas de Ribeir&#xe3;o Preto - Universidade de S&#xe3;o Paulo. CAAE number: 29848720.0.1001.5440.

Humans↗
PubMedDate not supplied

[Artificial arterial hypotension during surgical treatment of intracranial aneurysms].

In studying the content of lactic and pyruvic acids in the cerebrospinal fluid of 31 patients during operation for intracranial aneurysms under halothane anesthesia, the authors established that the performance of these operations under protection of deep (40 mm Hg) and prolonged (up to 2 hrs 25 min) artificial arterial hypotension in an uncomplicated course of the surgical intervention was not attended with hypoxic damage of the brain. The danger of hypoxia developing became greater when acute disturbances of blood flow in the cerebral arteries (clipping of a vessel, spasm) occurred in the period of hypotension.

Adult↗
PubMed1978

Intracranial saccular aneurysms--surgical results of 1,000 consecutive cases.

The results of our surgical treatment of 1,000 patients with intracranial saccular aneurysm were analyzed with special consideration for age, site of aneurysm, preoperative condition and operative timing. The results on discharge were as follows: 543 cases, excellent; 186, good; 117, fair; 93, poor; and 61, dead. About three-fourths of the cases except for 23 cases of vertebrobasilar aneurysm showed either excellent or good result. The mortality rate became worse with aging. The results fairly correlated with the preoperative grades by Hunt and Hess (1968), but the cases of Grade Ia were unexpectedly worse. The timing of operation influenced the mortality rate; especially, the cases operated within 3 to 7 days following the last subarachnoid hemorrhage bore poor results. Follow-up studies revealed that excellent and good cases increased and poor cases decreased. The mortality rate for each year decreased annually to 2% in 1975. This improvement may be attributed to the advancement in the operative management with supplementary procedures and in the treatment for cerebral angiospasms and general condition.

Adult↗
PubMed1979

[Diagnosis and pathological analysis of ruptured cerebral aneurysm by CT (author's transl)].

This report describes the analysis of 216 CT pictures of 85 patients with ruptured aneurysms which consist of 29 anterior communicating, 27 internal carotid, 27 middle cerebral and 2 basilar arterial aneurysms, including 18 cases with multiple aneurysms. The intervals between CT scanning and the last subarachnoid hemorrhage were various from 6 hours to 4 months. The first CT scanning was made in 40 cases within 3 days, in 54 cases within 7 days and in 11 cases more than one month after the hemorrhage. CT findings showed no abnormality in 9 patients who were classified as Grade I (Hunt and Kosnik) and examined more than 2 weeks after the subarachnoid hemorrhage. Seventy-six patients had some abnormal findings in the first CT scans, which were 55 cases of subarachnoid clot, 16 cases of intracerebral hematoma, 24 cases of intraventricular clot, 16 cases of low density suggesting brain edema or softening and 42 cases of ventricular enlargement. There was a good correlation between CT findings and clinical grade of Hunt and Kosnik. In Grade I and II, abnormal findings other than subarachnoid clot were seldom seen. Iin Grade III, there were intracerebral hematoma (20%), low density (20%) and frequent ventricular dilatation; in Grade IV, massive intracerebral hematoma (80%); in Grade V, massive intracerebral hematoma and ventricular tamponade with blood clot; in Grade Ia, moderate ventricular dilatation and/or diffuse cerebral infarction. Cerebral vasospasm could be anticipated by CT pictures because it occurred frequently in the patients with massive and long-standing subarachnoid blood clot. The determination of the side and location of the ruptured aneurysm was possible in 82% of the patients who had subarachnoid clot, intracerebral hematoma or low density. This is useful to decide the side of the first angiography and the aneurysm to be approached at first in the cases of multiple aneurysms.

Adolescent↗