Abstract
Older adult patients with sepsis frequently experience cognitive impairment. The roles of brain neutrophil gelatinase-associated lipocalin (NGAL) and iron in older sepsis patients remain unknown. We investigated the effects of lipopolysaccharide-induced sepsis on novel object recognition test, NGAL levels, an inflammatory mediator tumor necrosis factor-α (TNFα) levels, and iron ion levels in the hippocampus and cortex of young and aged rats. The effect of an iron chelator deferoxamine pretreatment on aged sepsis rats was also examined. Young sepsis-survivor rats did not show impaired novel object recognition, TNFα responses, or a Fe2+/Fe3+ imbalance. They showed hippocampal and cortical NGAL level elevations. Aged sepsis-survivor rats displayed a decreased object discrimination index, elevation of NGAL levels and Fe2+/Fe3+ ratio, and no TNFα responses. Pretreatment with deferoxamine prevented the reduction in the object recognition of aged sepsis-survivor rats. The elevation in hippocampal and cortical NGAL levels caused by lipopolysaccharide was not influenced by deferoxamine pretreatment. The lipopolysaccharide-induced Fe2+/Fe3+ ratio elevation was blocked by deferoxamine pretreatment. In conclusion, our findings suggest that iron homeostasis in the cortex and hippocampus contributes to the maintenance of object recognition ability in older sepsis survivors.
Highlights
Older adult patients with sepsis frequently experience cognitive impairment
We investigated the effects of systemic LPS injections on brain neutrophil gelatinase-associated lipocalin (NGAL) levels, tumor necrosis factor-α (TNFα) levels, iron ion levels, and object recognition in young and aged rats
There were significantly fewer survivors in the aged mg/kg LPS injection (A-LPS) group than the aged control (A-CON) group [hazard ratio (HR) 0.13, 95% CI 0.03–0.46; log-rank test, z = 2.80, P < 0.05]
Summary
Older adult patients with sepsis frequently experience cognitive impairment. The roles of brain neutrophil gelatinase-associated lipocalin (NGAL) and iron in older sepsis patients remain unknown. We investigated the effects of lipopolysaccharide-induced sepsis on novel object recognition test, NGAL levels, an inflammatory mediator tumor necrosis factor-α (TNFα) levels, and iron ion levels in the hippocampus and cortex of young and aged rats. Young sepsis-survivor rats did not show impaired novel object recognition, TNFα responses, or a Fe2+/Fe3+ imbalance They showed hippocampal and cortical NGAL level elevations. Ferric (Fe3+) and ferrous ions (Fe2+) are sources of reactive oxygen species and contribute to the aggregation of Amyloid-β, Tau, and α-synuclein[20] These findings suggest that NGAL and iron metabolism might have therapeutic potential for cognitive dysfunction associated with neuroinflammation and neurodegeneration. We investigated the effects of systemic LPS injections on brain NGAL levels, TNFα levels, iron ion levels, and object recognition in young and aged rats. We examined whether DFO treatment could ameliorate LPS-induced cognitive dysfunction in aged rats
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