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
- neuropathic pain
- lps induced
- cardiovascular events
- dendritic cells
- cancer therapy
- spinal cord
- multiple sclerosis
- oxidative stress
- genome wide
- physical activity
- endoplasmic reticulum stress
- type diabetes
- cognitive impairment
- spinal cord injury
- cystic fibrosis
- staphylococcus aureus
- dna methylation
- single molecule
- blood brain barrier
- drug delivery
- immune response
- case control