Cytokine-Mediated Mechanisms in Cerebral Ischemia

Cerebral ischaemia triggers a tightly orchestrated inflammatory response in which cytokines and chemokines released by resident glial cells and infiltrating leukocytes play central roles. Within minutes of arterial occlusion, damaged neurons and activated microglia secrete proinflammatory mediators such as interleukin-1β, tumour necrosis factor-α and interleukin-6, which propagate a cascade of blood–brain barrier disruption, endothelial activation and recruitment of neutrophils and monocytes. Signalling through mitogen-activated protein kinase and nuclear factor-κB pathways amplifies this response, while metabolic shifts in microglia—from oxidative phosphorylation to glycolysis—further sustain cytokine production. In later phases, anti-inflammatory cytokines including interleukin-10 and transforming growth factor-β promote resolution and tissue repair, though excessive or prolonged inflammation may exacerbate neuronal loss. Understanding these dynamic interplays has informed therapeutic strategies aimed at restoring vascular integrity, modulating glial phenotypes and targeting specific cytokine axes to limit secondary injury and improve functional recovery.

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Cytokine-Mediated Mechanisms in Cerebral Ischemia publication trend

The graph below shows the total number of articles in cytokine-mediated mechanisms in cerebral ischemia across all publications each year (not limited to Nature Index journals).

Technical terms

Cytokine: Signalling protein secreted by immune and glial cells to regulate inflammatory and reparative processes.

Chemokine: Subset of cytokines that directs migration of leukocytes through concentration gradients (chemotaxis).

Microglia: Innate immune cells of the central nervous system that detect injury and orchestrate neuroinflammatory responses.

Blood–Brain Barrier (BBB): Specialized endothelial layer that restricts passage of cells and molecules from blood into brain parenchyma.

Ischaemia–Reperfusion Injury: Tissue damage that arises when blood flow is restored after a period of ischaemia, often exacerbated by inflammatory mediators.

MAPK Pathway: Mitogen-activated protein kinase cascade that transduces extracellular stress signals to regulate gene expression and cytokine production.

AMPK–mTOR–HIF-1α Signalling: Metabolic regulatory axis linking cellular energy status to hypoxic and inflammatory gene programmes.

References

1. Neutralization of chemokine-like factor 1, a novel C-C chemokine, protects against focal cerebral ischemia by inhibiting neutrophil infiltration via MAPK pathways in rats. Journal of Neuroinflammation (2014).
2. IMM-H004 Protects against Cerebral Ischemia Injury and Cardiopulmonary Complications via CKLF1 Mediated Inflammation Pathway in Adult and Aged Rats. International Journal of Molecular Sciences (2019).
3. A breakdown of metabolic reprogramming in microglia induced by CKLF1 exacerbates immune tolerance in ischemic stroke. Journal of Neuroinflammation (2023).