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  • Title: Relationship between high-mobility group box-l and cognitive impairments induced by myocardial ischemia-reperfusion in elderly rats.
    Author: Yang W, Yu J, Wang H, He J, Pei R.
    Journal: Exp Gerontol; 2024 Oct 01; 195():112540. PubMed ID: 39122228.
    Abstract:
    BACKGROUND: Myocardial ischemia-reperfusion (MI/R) can lead to structural and functional abnormalities in the hippocampal neurons of the brain. High-mobility group box-l (HMGB1) is implicated in the activation of immune cells and the stimulation of inflammatory responses. However, the specific role of HMGB1 in cognitive impairment induced by MI/R in elderly rats has yet to be elucidated. METHODS: Elderly rats underwent surgical procedures to induce MI/R. To evaluate the learning and memory abilities of these rats, a water maze test and a new-object recognition test were administered. Nissl staining was utilised to examine hippocampal neuron damage. Enzyme-linked immunosorbent assay, western blotting, and real-time quantitative polymerase chain reaction (RT-qPCR) analyses were conducted to measure the expression levels of HMGB1, inflammatory cytokines, and molecular pathways. RESULTS: The study found that MI/R induced cognitive impairment in elderly rats. There was an observed increase in serum HMGB1 levels, along with elevated concentrations of pro-inflammatory cytokines in the plasma and hippocampus, accompanied by a decrease in anti-inflammatory cytokines. Moreover, substantial damage was evident in the hippocampal neurons of rats exposed to MI/R. In the brains of these rats, there was an increased expression of HMGB1, the receptor for advanced glycation end products (RAGE), toll-like receptor 4 (TLR4), phosphorylated p65, interleukin-1β (IL-1β), IL-6, IL-23, tumour necrosis factor-α (TNF-α), caspase-3, and Bax. In contrast, the expression of B-cell lymphoma 2 was decreased. The RT-qPCR analyses indicated elevated levels of HMGB1, RAGE, TLR4, IL-1β, IL-6, IL-23, TNF-α, caspase-3, and Bax mRNA. CONCLUSION: The increased concentration of serum and hippocampal inflammatory factors in the brains of elderly rats subjected to MI/R suggests that cognitive impairment may be induced through the activation of the HMGB1/TLR4/NF-κB signalling pathway.
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