Current Advances in Intracranial Aneurysms: From Basic to Clinical Research

Introduction: Intracranial aneurysms (IAs) are focal dilatations of cerebral arteries that carry a significant risk of rupture and subarachnoid hemorrhage (aSAH). Advances in basic science have improved understanding of vascular wall biology, hemodynamic stress, inflammation, and genetic contribution to aneurysm rupture. Rapid progress in neurovascular therapeutics highlights the need to evaluate emerging molecular and pharmacologic strategies targeting IAs. Methodology: This narrative review synthesizes evidence from 2015 to 2025 on the cellular, molecular, and biomechanical mechanisms underlying IA pathophysiology. A structured search of PubMed, Scopus, and Embase identified studies examining molecular pathways, genetic determinants, and therapeutic approaches. Discussion: Aneurysm initiation involves endothelial responses to abnormal shear stress, activating NF-κB, MAPK, and calcium-dependent pathways that promote inflammation, smooth-muscle cell apoptosis, and extracellular matrix degradation. Pharmacologic candidates including MCP-1 antagonists, PPARγ agonists, and IL-6/STAT3 inhibitors reduce inflammatory remodeling, while doxycycline and cathepsin inhibitors preserve matrix integrity. Emerging strategies like microRNA modulation, tyrosine-kinase inhibition, and gene-based delivery offer potential for localized, durable stabilization with minimal systemic toxicity. Conclusions: Integrating surgical and biologic therapies may shift IA management from reactive repair to rupture prevention. Full article

Background/Objectives: Aneurysms develop secondary to progressive weakening of arterial walls and remain a major cause of morbidity and mortality worldwide. Collagen, particularly fibrillar types I and III, is the primary tensile load-bearing component of arteries, yet its specific role in aneurysm formation, progression, and rupture is incompletely defined. This narrative review synthesizes current evidence on collagen structure, regulation, and degradation in aneurysm pathophysiology, highlighting cerebral aneurysms within the broader context of aneurysms as a whole. Methods: Searches of PubMed, MEDLINE, Embase, and Google Scholar were performed to identify all English-language studies published prior to January 2026. Search terms included “cerebral aneurysm”, “collagen”, “extracellular matrix”, “vascular remodeling”, and “aneurysm rupture”. Included studies evaluated collagen structure or content, extracellular matrix remodeling, matrix metalloproteinases, or biomechanical properties of the aneurysm wall in experimental or human models. Results: The literature search identified 348 records, of which 87 studies published between 1999 and 2025 met the inclusion criteria and were synthesized in this review. Collagen types I and III form the primary tensile scaffold of intracranial arteries, while basement membrane and regulatory collagens (e.g., types IV, V, and VI) modulate fibril organization, endothelial stability, and mechanical homeostasis. Research demonstrates that endothelial dysfunction, nitric oxide dysregulation, oxidative stress, and matrix metalloproteinase activation are key pathways driving collagen fragmentation and degradation. Genetic and epigenetic disturbances in collagen and related extracellular matrix pathways further increase aneurysm susceptibility. Conclusions: Collagen dysregulation appears to be a final common pathway through which hemodynamic, inflammatory, hormonal, and genetic insults converge to weaken intracranial arterial walls. However, existing evidence is dominated by animal and aortic models, and in vivo tools, such as Magnetic Resonance Imaging with collagen-sensitive sequences and Positron Emission Tomography Tracers, to quantify collagen integrity in cerebral aneurysms are lacking. Future efforts should prioritize human-focused studies, advanced collagen-sensitive imaging, biomarker development, and targeted strategies to preserve or restore collagen structure as potential means to improve aneurysm risk stratification, prevention, and treatment. Full article

Background/Objectives: Unruptured intracranial aneurysms (UIAs) carry a risk of subarachnoid hemorrhage (SAH), which has a high mortality rate of up to 45% and significant long-term disability among survivors. Traditional surgical clipping and endovascular treatment (EVT) are widely used, but both have limitations: EVT shows higher recurrence and retreatment rates, while open clipping poses higher procedural risks. Minimally invasive craniotomy (MIC) techniques are emerging as a promising third option, offering potential benefits in terms of safety, durability, and recovery. This study aims to compare MIC and EVT for UIAs to evaluate their relative efficacy, safety, and long-term outcomes. Methods: A systematic literature review was conducted using PubMed and Scopus. Inclusion criteria encompassed original, peer-reviewed studies reporting clinical outcomes of UIA treatments. Data extracted included study characteristics, treatment modality, complication rates, recurrence, retreatment, and patient outcomes. Results: MIC demonstrated low complication rates (1.6–5.88%), for which the percentage was significantly lower than that for stent-assisted coiling (37%) and flow diversion (17%), while maintaining similar efficacy to traditional clipping. New EVT techniques such as WEB devices showed less procedural risks (0.7%) but higher retreatment rates. Conclusions: This review shows that while traditional craniotomy for aneurysm clipping carries higher perioperative risk than EVT, most studies have failed to compare long-term recurrences. MIC has significantly lower perioperative complications rates, comparable to EVT, and provides the same durability with improved cosmetic results. MIC should be considered when selecting patients as an alternative to EVT, particularly for unruptured anterior circulation aneurysms. Further prospective studies are needed to guide treatment decisions. Full article

Background: Intracranial fusiform aneurysms represent a rare but clinically aggressive subtype of cerebrovascular disease, characterized by circumferential arterial dilation and a high risk of growth, ischemic complications, and rupture. Unlike saccular aneurysms, fusiform lesions lack well-established medical therapies to prevent progression or stabilize the aneurysm wall. Tumor necrosis factor-alpha (TNF-α) has emerged as a central mediator of aneurysm-associated inflammation and vascular remodeling, raising interest in TNF-α modulation as a potential therapeutic strategy. This study aimed to systematically review and synthesize the available clinical and translational evidence evaluating TNF-α signaling and anti-TNF-α therapies in the context of intracranial fusiform aneurysms. Methods: A systematic literature search was conducted in PubMed/MEDLINE, Embase, and Google Scholar from database inception through February 2026 in accordance with PRISMA guidelines. Eligible studies included human, animal, and translational investigations examining TNF-α biology or anti-TNF-α interventions in relation to intracranial fusiform aneurysms, intracranial dolichoectasia, or vertebrobasilar dolichoectatic aneurysms. Study selection, deduplication, and screening were performed using Covidence systematic review software. Extracted outcomes included aneurysm growth, rupture, ischemic events, imaging characteristics, inflammatory signaling, and vascular remodeling. Given substantial heterogeneity in study design and outcome reporting, findings were synthesized narratively using structured evidence mapping. Results: From the 368 records identified, 14 studies met inclusion criteria following full-text review. Included studies encompassed preclinical models, translational mechanistic investigations, and limited clinical observational data. Across experimental models, TNF-α signaling was consistently associated with macrophage infiltration, matrix metalloproteinase activation, vascular smooth muscle cell phenotypic modulation, and aneurysm wall degeneration. TNF-α inhibition was associated with reduced aneurysm progression and rupture in preclinical settings, including when initiated after aneurysm formation. Clinical evidence remains limited but suggests a potential association between TNF-α modulation and aneurysm stability, although direct therapeutic data in intracranial fusiform aneurysm populations are sparse. Conclusions: The existing translational and preclinical evidence supports a contributory role for TNF-α-mediated inflammation in the progression of intracranial fusiform aneurysms and suggests that TNF-α inhibition may represent a promising disease-modifying strategy. However, clinical data remain insufficient to support routine therapeutic use. Prospective observational studies and early-phase clinical trials are needed to define the safety, timing, and efficacy of anti-TNF-α therapies in patients with intracranial fusiform aneurysms. Full article