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<p>Activation of α-2 adrenergic receptors (AR) may exert a protective role against neuronal injury. Clinically, dexmedetomidine (DEX), a selective α-2 AR agonist, has been shown to reduce brain dysfunction. Therefore, the aim of this study was to investigate whether DEX could prevent cognitive deficits induced by sepsis. Wistar rats were randomly assigned to five groups: (1) Sham; (2) sepsis induced by cecal ligation and puncture (CLP); (3) CLP + DEX; (4) CLP + idazoxan (IDA, an α-2 AR antagonist); and (5) CLP + IDA + DEX. At different time points after CLP, the hippocampus, prefrontal cortex, and amygdala were isolated for quantification of cytokines, α-2A and α-2C AR expression, and glutamate content. At 10 and 30&#xa0;days post-CLP, cognitive function was assessed using the open field habituation, inhibitory avoidance, and novel object recognition tasks. DEX treatment improved performance across all cognitive tasks, and this effect was antagonized by co-administration of IDA. DEX reduced proinflammatory cytokine levels (IL-6 and IL-1β) 24&#xa0;h after sepsis, and this anti-inflammatory effect was sustained at later time points, particularly for IL-1β in the hippocampus. Additionally, DEX decreased glutamate levels in the pre-frontal cortex and amygdala late after sepsis induction. DEX also regulated the expression of α-2 AR subtypes in a time- and region-specific manner. In conclusion, the protective effect of DEX on cognitive function appears to be the mainly affected by the regulation of glutamate levels, whose effects were receptor-dependent, in contrast to the majority of cytokines. However, it should be noted that the primary neuroprotective effect is driven by the direct, receptor-dependent functional agonism of DEX administered acutely after sepsis induction, and this acute mechanism subsequently triggers secondary, long-term structural adaptations that ultimately influence cognitive function.</p>

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Effects of Treatment with Dexmedetomidine on Neurochemical and Cognitive Alterations Induced by Sepsis in an Animal Model

  • 期刊论文

  • 发表日期：

    2025年12月6日

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  • Mariane Abatti,
  • Luana Cucker,
  • Andriele Vieira,
  • Monique Michels,
  • Amanda Goulart,
  • Heloisa Borges,
  • Rodrigo Dias,
  • Emily Corneo,
  • Diogo Dominguini,
  • Ingrid Farias,
  • Flávio Henrique Reginatto,
  • Cristiane Ritter,
  • Felipe Dal-Pizzol

摘要

Activation of α-2 adrenergic receptors (AR) may exert a protective role against neuronal injury. Clinically, dexmedetomidine (DEX), a selective α-2 AR agonist, has been shown to reduce brain dysfunction. Therefore, the aim of this study was to investigate whether DEX could prevent cognitive deficits induced by sepsis. Wistar rats were randomly assigned to five groups: (1) Sham; (2) sepsis induced by cecal ligation and puncture (CLP); (3) CLP + DEX; (4) CLP + idazoxan (IDA, an α-2 AR antagonist); and (5) CLP + IDA + DEX. At different time points after CLP, the hippocampus, prefrontal cortex, and amygdala were isolated for quantification of cytokines, α-2A and α-2C AR expression, and glutamate content. At 10 and 30 days post-CLP, cognitive function was assessed using the open field habituation, inhibitory avoidance, and novel object recognition tasks. DEX treatment improved performance across all cognitive tasks, and this effect was antagonized by co-administration of IDA. DEX reduced proinflammatory cytokine levels (IL-6 and IL-1β) 24 h after sepsis, and this anti-inflammatory effect was sustained at later time points, particularly for IL-1β in the hippocampus. Additionally, DEX decreased glutamate levels in the pre-frontal cortex and amygdala late after sepsis induction. DEX also regulated the expression of α-2 AR subtypes in a time- and region-specific manner. In conclusion, the protective effect of DEX on cognitive function appears to be the mainly affected by the regulation of glutamate levels, whose effects were receptor-dependent, in contrast to the majority of cytokines. However, it should be noted that the primary neuroprotective effect is driven by the direct, receptor-dependent functional agonism of DEX administered acutely after sepsis induction, and this acute mechanism subsequently triggers secondary, long-term structural adaptations that ultimately influence cognitive function.