Efficacy of atorvastatin on hippocampal neuronal damage caused by chronic intermittent hypoxia: Involving TLR4 and its downstream signaling pathway

• Hippocampal neurons damage was found in a chronic intermittent hypoxia (CIH) mice model of obstructive sleep apnea syndrome (OSAS).
• Toll-like receptor 4 (TLR4) and its two downstream factors myeloid differentiation factor 88 (MYD88) and TIR-domain-containing adapter-inducing interferon-β (TRIF), along with the inflammatory agents and oxidative stress were increased in the hippocampus of mice exposed to CIH.
• Atorvastatin contributed to the neuroprotection and the beneficial effects of atorvastatin may involve inhibiting TLR4 signaling pathway.
• These provide further insights into the mechanism and treatment for neural injury of OSAS.

Hippocampal neuronal damage is critical for the initiation and progression of neurocognitive impairment accompanied obstructive sleep apnea syndrome (OSAS). Toll-like receptor 4 (TLR4) plays an important role in the development of several hippocampus-related neural disorders. Atorvastatin was reported beneficially regulates TLR4. Here, we examined the effects of atorvastatin on hippocampal injury caused by chronic intermittent hypoxia (CIH), the most characteristic pathophysiological change of OSAS.Mice were exposed to intermittent hypoxia with or without atorvastatin for 4 weeks. Cell damage, the expressions of TLR4 and its two downstream factors myeloid differentiation factor 88 (MYD88) and TIR-domain-containing adapter-inducing interferon-β (TRIF), inflammatory agents (tumor necrosis factor α and interleukin 1β), and the oxidative stress (superoxide dismutase and malondialdehyde) were determined.Atorvastatin decreased the neural injury and the elevation of TLR4, MyD88, TRIF, pro-inflammatory cytokines and oxidative stress caused by CIH.Our study suggests that atorvastatin may attenuate CIH induced hippocampal neuronal damage partially via TLR4 and its downstream signaling pathway.