The Middle Meningeal Artery (MMA) occupies a pivotal role in the pathophysiology of migraine, functioning as a vascular and neuroimmune interface that precipitates the characteristic pulsatile pain. The inhibition of this pathophysiological cascade has been investigated as a therapeutic strategy. However, fewer than a dozen centers globally have disseminated procedural or mechanistic data. Given the nascency of this field and the imperative for standardization, the present review synthesizes mechanistic and clinical evidence underpinning intra-arterial pharmacological modulation of the MMA for migraine management. Methods: A focused narrative review was undertaken, drawing upon select but influential studies from pioneering research groups investigating intra-arterial interventions targeting the MMA. The extant literature was thematically categorized and organized according to the loci of cascade interruption and their corresponding clinical outcomes. Results: Since 2009, intra-arterial therapies for severe headache syndromes have evolved, initially utilizing nimodipine for vasospasm-related headaches, progressing to verapamil for reversible cerebral vasoconstriction, and more recently, lidocaine for refractory or status migrainosus, occasionally in conjunction with MMA embolization. Contemporary research uses language that conceptualizes migraine as an immunologically mediated neurovascular disorder, as opposed to a purely vascular or neuronal entity. Recent investigations have identified interleukins such as Interleukin-1β, Tumor Necrosis Factor-α, and Interleukin-6 as critical amplifiers of trigeminovascular activation. Purinergic signaling through the P2X3 receptor and the P2Y13 receptor, in conjunction with pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal peptide pathways, has been implicated in the modulation of MMA excitability and neuropeptide release. The development of novel calcitonin gene-related peptide receptor antagonists, such as zavegepant, further substantiates the artery’s significance as a pharmacological target. Conclusions: These findings support a shift toward immune-modulating intra-arterial therapeutic strategies, with migraine interventions targeting cytokine and neuroimmune signaling within the MMA, rather than relying exclusively on vasodilatory mechanisms.

Ischemic heart disease remains the most significant cause of morbidity and mortality worldwide. Althoughconventional therapies such as β-blockers, ACE inhibitors, statins, and percutaneous coronary intervention havereduced mortality in industrialized nations, progress has plateaued, and global ischemic burden continues to rise.Renewed scientific attention has turned to canonical cardioprotective signaling pathways with a level of molecularprecision not previously feasible. Parallel advances in exercise biology and mesenchymal stem-cell derived exosome(MSC-EXO) research suggest an opportunity for integrative cardioprotection. Exercise, once understood primarilyin descriptive physiologic terms, is now recognized as a complex molecular stimulus that can activateredox-sensitive kinases, autophagy regulators, and metabolic remodeling pathways. New state-of-the-artinvestigations have gone towards decoding this “exercise secretome” and developing tools to modulate thesechemical cascades. Multiple experimental studies report that MSC-derived exosomes function as biologically activeparacrine vectors that deliver regulatory microRNAs and proteins to recipient cells and promote angiogenesis,suppress apoptosis, and support mitochondrial function. This narrative review assesses the effectiveness ofinterventions on canonical pathways such as ERK and AKT/mTOR on ISO-induced ischemic injury models to theheart based on recent animal and human studies. Supporting literature on stem cell biology, exosome deliverystrategies, and translational barriers is discussed to create an integrated framework that reinforces and sustainsreparative signaling in ISO-induced ischemic environments. Together, these two rapidly evolving fields, exercisebiology and MSC-ECO, may define the next frontier in regenerative ischemic cardiomyopathy by harnessing innaterepair pathways and bioengineered tools to potentiate the crosstalk among metabolic, kinase, and paracrine survivalcircuits.

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.

Background: The middle meningeal artery (MMA) plays a central role in migraine pathophysiology as a vascular and neuroimmune interface driving the throbbing pain. Inhibition of this cascade has been explored as a therapeutic approach, yet fewer than a dozen centers worldwide have published procedural or mechanistic data. Given the nascency of this field and the need for standardization, this review synthesizes the mechanistic and clinical evidence supporting intra-arterial pharmacologic modulation of the MMA for migraine treatment. Methods: A focused narrative review was conducted using limited but high-impact studies from pioneering groups exploring intra-arterial approaches to the MMA. Literature was arranged thematically and organized by the sites of cascade interruption and associated outcomes. Results: Since 2009, the use of intra-arterial therapies for severe headache syndromes has evolved from nimodipine for vasospasm-related headaches to verapamil for reversible cerebral vasoconstriction and, more recently, lidocaine for refractory or status migrainosus cases, sometimes with MMA embolization. Current research reframes migraines as an immunologically mediated neurovascular process, rather than purely a vascular or neuronal phenomenon. Recent studies have identified interleukins such as IL-1β, TNF-α, and IL-6 as key amplifiers of trigeminovascular activation, while emerging evidence implicates purinergic (P2X3, P2Y13) and PACAP/VIP pathways in modulating MMA excitability and neuropeptide release. Novel CGRP receptor antagonists, including zavegepant further reinforce the artery’s role as a therapeutic target. Conclusion: Our findings highlight a transition toward immune-modulating intra-arterial strategies, suggesting that future migraine therapies may increasingly focus on cytokine and neuroimmune signaling within the MMA rather than traditional vasodilatory control.