Primary subarachnoid hemorrhage (SAH) is a type of acute stroke, accounting for approximately 10% of cases, with high disability and mortality rate. Early brain injury (EBI) is a critical factor in determining SAH mortality; however, there are no effective treatment interventions for EBI. Based on our results, the transmission of cyclic GMP-AMP (cGAMP) from neurons to microglia is a key molecular event that triggers type I interferon response, amplifies neuroinflammation, and leads to neuronal apoptosis. Abnormal intracytoplasmic mitochondrial DNA (mtDNA) is the initiating factor of the cGAS-cGAMP-STING signaling axis. Overall, the cGAS-cGAMP-STING signaling axis is closely associated with neuroinflammation after subarachnoid hemorrhage. Targeting cGAS triggered by cytoplasmic mtDNA may be useful for comprehensive clinical treatment of patients after SAH. Further studies targeting cGAS-specific antagonists for treating SAH are warranted. Video Abstract.
Keyphrases
- subarachnoid hemorrhage
- mitochondrial dna
- brain injury
- cerebral ischemia
- copy number
- inflammatory response
- lipopolysaccharide induced
- lps induced
- neuropathic pain
- dendritic cells
- cardiovascular events
- cancer therapy
- traumatic brain injury
- spinal cord
- oxidative stress
- risk factors
- multiple sclerosis
- genome wide
- cell cycle arrest
- type diabetes
- cognitive impairment
- cell proliferation
- gene expression
- single molecule
- cystic fibrosis
- dna methylation
- pseudomonas aeruginosa
- replacement therapy