Figure 1.

Initiation and amplification of mitochondrial dysfunction in SAH.

After SAH, mitochondria are directly affected by ischemia and hypoxia, excitotoxicity, and toxicity of hemoglobin and its degradation products, which trigger mitochondrial dysfunction and lead to the collapse of ΔΨm. Subsequently, mitochondrial dysfunction leads to the massive production of mtROS, release of mtDAMP, and activation of the mitochondrial apoptotic pathway. Simultaneous excitotoxicity increases the Ca²⁺ inward flow, triggering calcium-dependent MPT, which further increases ROS production and apoptotic protein release. This process ultimately leads to oxidative stress, inflammation, and apoptosis, amplifying cellular damage. Created using used Adobe Illustrator 2021, with material from Servier Medical Art. AMPA: α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; Apaf1: apoptotic protease-activating factor 1; Bax/Bak: BCL2-associated X/BCL2 antagonist/killer 1; CytC: cytochrome c; Hb: hemoglobin; MPT: mitochondrial permeability transition; mtDAMP: mitochondrial damage-associated molecular patterns; mtROS: mitochondrial reactive oxygen species; NMPA: N-methyl-D-aspartate; ROS: reactive oxygen species; SAH: subarachnoid hemorrhage; ΔΨm: mitochondrial membrane potential.