Mitochondrial dysfunction in cerebrovascular diseases
Opening of the mitochondrial permeability transition pore, Ca2+ overload, and mitochondrial fragmentation are early features of stroke-induced brain injury observed in experimental models.
Mitochondrial reactive oxygen species and activation of the cyclophilin D– reactive oxygen species–NLR family pyrin domain-containing 3–matrix metalloproteinase-9 axis are associated with intracranial aneurysm progression, linking mitochondrial stress to vascular wall instability.
Disruption of mitochondrial homeostasis exacerbates vascular pathology in intracranial atherosclerotic stenosis, arteriovenous malformations, and cavernous malformation, indicating a shared mitochondrial contribution across cerebrovascular disorders.
Pharmacological modulation of mitochondrial permeability, redox signaling, proprotein convertase subtilisin/ kexin type 9, and mechanistic target of rapamycin kinase pathways shows robust preclinical efficacy, while clinical outcomes remain heterogeneous.
Experimental studies support the feasibility of mitochondrial transplantation in models of cerebrovascular injury, including stroke.
https://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(26)00084-5
