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

Author(s)

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

• Document type: Journal article
• Source: BRAIN, BEHAVIOR, & IMMUNITY - HEALTH; v. 31, p. 10-pg., 2023-08-01.

Abstract

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 antiinflammatory 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. (AU)

• FAPESP's process: 16/17681-9 - Pathophysiological changes during systemic inflammation
• Grantee: Luiz Guilherme de Siqueira Branco
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/09878-0 - Effect of vagal stimulation during LPS immune challenge in normotensive and spontaneously hypertensive rats
• Grantee: Mateus Ramos Amorim
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 16/01607-4 - High intensity sound stimulation and synaptic plasticity
• Grantee: Ricardo Mauricio Xavier Leão
• Support Opportunities: Regular Research Grants