Programmed Cell Death: A Key Pathway in Intracranial Aneurysm Progression

Intracranial aneurysm (IA) is a common cerebrovascular disease characterized by abnormal bulging of the intracranial arterial wall, with high potential risk of rupture and severe clinical consequences. As a major subtype of IAs, middle cerebral artery aneurysm (MCAA) accounts for 30%–40% of all IA cases, mainly occurring at the M1-M2 segment bifurcation of the middle cerebral artery. Most IAs, including MCAAs, are asymptomatic initially, but rupture can lead to life-threatening complications such as subarachnoid hemorrhage and intracerebral hematoma, with an acute-phase mortality rate of 30%–50%. Nearly half of survivors suffer from permanent neurological deficits (e.g., limb hemiplegia, cognitive impairment), imposing a heavy burden on families and society.The core pathogenesis of IAs involves structural damage of the vascular wall and imbalance of cellular homeostasis. Congenital defects (such as discontinuous internal elastic lamina and sparse smooth muscle cells) at the arterial bifurcation, combined with acquired factors (abnormal shear stress, chronic inflammation), reduce the tensile strength of the vascular wall, eventually leading to the formation of aneurysmal bulges. Apoptosis regulates the survival of vascular wall cells and participates in the pathological process of IA formation and progression. Atypical programmed cell death (e.g., ferroptosis, pyroptosis, autophagy-dependent death) also plays an important role in driving the initiation and progression of IAs, including MCAAs.Reviewing these mechanisms is of great significance: it clarifies the interaction between various pathways, provides potential molecular targets for drug intervention, and lays a foundation for individualized rupture risk assessment of IAs, which helps break the dilemma of clinical early intervention and improve the prognosis of patients.