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Fig. 2 | Intensive Care Medicine Experimental

Fig. 2

From: Ischaemic stroke-induced distal organ damage: pathophysiology and new therapeutic strategies

Fig. 2

Mechanisms of immunomodulation and cell apoptosis induced by the dopamine pathway. Under normal conditions, dopamine activates type 1 receptors (DRD1), promoting cell survival. The increased release of dopamine triggered by non-protective mechanical ventilation activates type 2 receptors (DRD2), triggering a cascade of events resulting in apoptosis. Activation of astrocytic DRD2 induces upregulation and nuclear translocation of the αB-crystallin CRYAB/STAT3 pathway, which alleviates neuroinflammatory injury by reducing the generation of pro-inflammatory cytokines. In this context, dopamine agonists and antagonists can play a role in regulating the neuroinflammatory response; in particular, haloperidol—which competitively blocks postsynaptic dopamine receptors in the mesolimbic dopaminergic system—has different effects on cell survival depending on the use of protective and non-protective ventilation. Sinomenine can blunt the CRYAB/STAT3 pathway by acting on DRD2 receptors, thus suppressing neuroinflammation

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