NF-κB-Mediated Inflammation in the Pathogenesis of Intracranial Aneurysm and Subarachnoid Hemorrhage. Does Autophagy Play a Role?

Abstract

The rupture of saccular intracranial aneurysms (IA) is the commonest cause of non-traumatic subarachnoid hemorrhage (SAH)—the most serious form of stroke with a high mortality rate. Aneurysm walls are usually characterized by an active inflammatory response, and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) has been identified as the main transcription factor regulating the induction of inflammation-related genes in IA lesions. This transcription factor has also been related to IA rupture and resulting SAH. We and others have shown that autophagy interacts with inflammation in many diseases, but there is no information of such interplay in IA. Moreover, NF-κB, which is a pivotal factor controlling inflammation, is regulated by autophagy-related proteins, and autophagy is regulated by NF-κB signaling. It was also shown that autophagy mediates the normal functioning of vessels, so its disturbance can be associated with vessel-related disorders. Early brain injury, delayed brain injury, and associated cerebral vasospasm are among the most serious consequences of IA rupture and are associated with impaired function of the autophagy–lysosomal system. Further studies on the role of the interplay between autophagy and NF-κB-mediated inflammation in IA can help to better understand IA pathogenesis and to identify IA patients with an increased SAH risk.

Systemic exosomal miR-193b-3p delivery attenuates neuroinflammation in early brain injury after subarachnoid hemorrhage in mice

“…Recent studies reported that HDCA3 inhibition appears to suppress NF-κB transcriptional activity by maintaining the NF-κB p65 acetylated (inactive) state and restraining the inflammatory response [33,43]. The NF-κB signaling pathway occurs in passive post-injury necrosis and in damaged cells, activating microglia to secrete inflammatory cytokines and causing amplification of the inflammatory response cascade [44,45]. In the present study, we found that levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α) in brain tissue increased after SAH, associated with apoptosis (caspase-3, BCL-2), brain edema, and neurological defects.…”

The vascular protective role of oestradiol: a focus on postmenopausal oestradiol deficiency and aneurysmal subarachnoid haemorrhage

“…Oestradiol supplementation/IL‐17A blockade reversed this effect (Hoh et al ., ). NF‐κB upregulates the expression of cytokines such as IL‐1, IL‐6, TNFα, chemokines (MCP‐1) and cell‐adhesion molecules (Aoki et al ., ; Saito et al ., ; Pawlowska et al ., ). Oestradiol suppresses the inflammatory responses of these pro‐inflammatory molecules by inhibiting NF‐κB activation and the subsequent autoregulated feedback loop (Ghisletti et al ., ; Jiang et al ., ; Xing et al ., ).…”

Cigarette smoke‐induced HMGB1 translocation and release contribute to migration and NF‐κB activation through inducing autophagy in lung macrophages

“…5, 31 We asked whether inhibition of autophagy by CQ or 3-MA had any effect on CSE-induced migration and NF-κB activation of lung macrophages. 5, 31 We asked whether inhibition of autophagy by CQ or 3-MA had any effect on CSE-induced migration and NF-κB activation of lung macrophages.…”

“…Previous studies found that autophagy mediated regulation of macrophage recruitment and NF-κB signalling pathway. 5,31 We asked…”