Inhaled molecular hydrogen reduces hippocampal neuroinflammation, glial reactivity and ameliorates memory impairment during systemic inflammation

Alexandra Olimpio Siquera Cunha, Aline Alves Jesus, Evelin Capellari Carnio, Junia Lara de Deus, Luiz G. S. Branco, Mateus Ramos Amorim, Procopio Cleber Gama de Barcellos Filho, Ricardo Mauricio Leao, Rui Milton Patricio da Silva Junior

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DOI: 10.1016/j.bbih.2023.100654 DOI is the universal ID for this study.

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Sepsis is associated with numerous physiological and biochemical abnormalities that result in a life-threatening condition. The involvement of the Central Nervous System (CNS) during sepsis has received considerable attention, especially the hippocampus which plays a key role in the learning and memory processes. The increased interest in this limbic region during systemic inflammation (SI) is related to the number of sepsis survivor patients who have cognitive impairments. A single injection of lipopolysaccharide (LPS)-induced systemic inflammation is the most commonly used murine endotoxemia model because it replicates several pathophysiological changes observed in severe sepsis. Molecular hydrogen (H2) has been used as an anti-inflammatory therapeutic strategy to prevent neuroinflammation. However, the mechanisms by which inhaled H2 mitigate memory loss during SI remains unknown. To understand how H2 acts in the hippocampus, the current study focused on specific mechanisms that may be involved in reducing neuroinflammation in rats during SI. We hypothesized that inhaled H2 decreases LPS-induced hippocampal pro-inflammatory cytokines surges and this effect is associated with reduced memory loss. Using different and integrative approaches, i.e., from hippocampal cells electrophysiology to animal behavior, we report that inhaled H2 decreased LPS-induced peripheral and hippocampal inflammation, decreased microglial and astrocytic activation, lessen memory loss without affecting long-term potentiation (LTP). To our knowledge, this is the first evidence showing that inhaled H2 reduces hippocampal microglial and glial cells inflammation, which may be associated with a reduced memory impairment induced by SI.

Publish Year 2023
Country Brazil
Rank Positive
Journal Brain, Behavior, & Immunity - Health
Primary Topic Brain
Secondary TopicSepsis
Model Rat
Tertiary TopicCognitive Impairment
Vehicle Gas
pH N/A
Application Inhalation