The dual role of the inflammatory response in ischemic stroke (IMAGE)
Caption
Cellular death within the infarcted core occurs rapidly due to energy depletion, resulting in the release of DAMPs such as HMGB1, ATP, and HSPs. These DAMPs engage pattern recognition receptors, including Toll-like receptors (TLR2 and TLR4) and scavenger receptors, thereby initiating innate immune responses. For instance, the interaction of HMGB1 with TLR4 activates the NF-κB signaling pathway, which subsequently induces the expression of pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6. This cascade promotes the infiltration of peripheral immune cells, leading to disruption of the blood-brain barrier, exacerbation of cerebral edema, and neuronal cell death. Concurrently, ROS generated from mitochondrial damage further amplify inflammatory signaling through oxidative stress, establishing a detrimental feedback loop. Conversely, a moderate inflammatory response is essential for tissue repair and functional recovery. Anti-inflammatory cytokines, including IL-10 and TGF-β, play a pivotal role in mitigating excessive inflammation, thereby facilitating nerve regeneration and angiogenesis. The figure was generated using Figdraw (https://www.figdraw.com/ ). ATP, adenosine triphosphate; DAMPs, damage-associated molecular patterns; HMGB1, high mobility group protein B1; HSPs, heat shock proteins; IL, interleukin; NF-κB, nuclear factor kappa B; ROS, reactive oxygen species; TGF-β, transforming growth factor-beta; TLR2, Toll-like receptor 2; TNF-α, tumor necrosis factor-alpha.
Credit
Shun Li, Tianqing Xiong
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License
CC BY-NC