Melatonin Attenuates the Inflammatory Response of Astrocyte Following Ischemia Stroke through SIRT1/NF-κΒ Signaling Pathway

Ischemic stroke (IS) remains a significant health burden with high rates of disability and mortality. Rapid reperfusion is critical for treating IS, yet paradoxically, it induces reperfusion injury. Astrocytes, the most abundant glial cells in the CNS, are increasingly recognized for their role in neuroinflammation and tissue repair post-ischemia. Silent information regulator 2 homolog 1 (SIRT1), a NAD + -dependent deacetylase, has emerged as a key regulator of cell survival, metabolism, and neuroprotection. Melatonin, an endogenous hormone with potent anti-inflammatory properties, has demonstrated the ability to mitigate neuroinflammatory processes, including the modulation of microglial activation through upregulation of the expression of SIRT1. However, the role of melatonin in the activation of inflammation in astrocytes after ischemic stroke remains unclear. This study investigates the role of melatonin in modulating astrocyte inflammatory activation following ischemic stroke and explores the potential involvement of SIRT1. Using rat models of transient middle cerebral artery occlusion and reperfusion (tMCAO/R) and in vitro oxygen-glucose deprivation/reperfusion (OGD/R) injury in primary astrocytes, we demonstrate that melatonin treatment significantly reduces inflammation by enhancing SIRT1-mediated deacetylation of NF-κB, a critical regulator of inflammatory responses. Our findings suggest that the melatonin-SIRT1 axis may represent a novel therapeutic target for the treatment of ischemic stroke, highlighting the potential of pharmacological interventions that harness this pathway to attenuate neuroinflammation and promote neuroprotection.