Purpurogallin ameliorates sevoflurane-induced cognitive impairment and hippocampal neuroinflammation in neonatal mice

Postoperative cognitive dysfunction contributes to memory impairment, which is involved in neurotoxicity, endoplasmic reticulum stress, calcium overload and hippocampal neuron apoptosis. Purpurogallin can mitigate ischemia-induced neuronal injury and microglial inflammation. However, whether purpurogallin affects cognitive dysfunction remains unclear. To investigate the efficacy of purpurogallin on cognitive dysfunction and explore the potential signal pathways, Sevoflurane (SEV)-induced model was established on mice, and water maze testing was performed to record escape latency, platform residence time, platform crossings and swimming speed analysis. The concentration of Interleukin (IL)-6, IL-1β and Tumor necrosis factor (TNF)-α in hippocampus tissue were evaluated using Enzyme-linked immunosorbent assay (ELISA). The hippocampal neurons were analyzed using Nissl staining. The Iba-1 was evaluated using immunofluorescent assay (IFA), while the cell apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Western blots were performed to evaluate the expression of Ionized calcium binding adaptor molecule 1 (Iba1), integrin α-M (CD11b), Bax, integrin α-M (Bcl-2), p-65 and IκBα, as well as the phosphorylation of p-65 and IκBα. Purpurogallin at dose of 150 mg/kg significantly reduced escape latency in SEV-induced mice (p < 0.001), without affecting swimming speed. It increased time spent in the target quadrant and restored platform crossings reduced by SEV. Purpurogallin also mitigated the elevated IL-6, IL-1β and Transforming growth factor alpha (TGF-α) levels caused by SEV in the hippocampus, preserved Nissl bodies, and reduced Iba-I and CD11b expression (p < 0.01). It alleviated cell apoptosis by downregulating Bax and upregulating Bcl-2, while inhibiting p-65 phosphorylation and promoting IκBα phosphorylation induced by SEV (p < 0.05). Purpurogallin effectively countered SEV-induced cognitive impairment, neuroinflammation, hippocampal injury, microglial activation and neuronal apoptosis through inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, which facilitate purpurogallin to become a drug candidate for postoperative cognitive dysfunction.

Cognitive dysfunction; Microglial activation; Neuronal apoptosis; NF-κB pathway; Neuroinflammation; Purpurogallin

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