What Animal Models Can Tell Us About Long-Term Psychiatric Symptoms in Sepsis Survivors: a Systematic Review

Abstract

Lower sepsis mortality rates imply that more patients are discharged from the hospital, but sepsis survivors often experience sequelae, such as functional disability, cognitive impairment, and psychiatric morbidity. Nevertheless, the mechanisms underlying these long-term disabilities are not fully understood. Considering the extensive use of animal models in the study of the pathogenesis of neuropsychiatric disorders, it seems adopting this approach to improve our knowledge of postseptic psychiatric symptoms is a logical approach. With the purpose of gathering and summarizing the main findings of studies using animal models of sepsis-induced psychiatric symptoms, we performed a systematic review of the literature on this topic. Thus, 140 references were reviewed, and most of the published studies suggested a time-dependent recovery from behavior alterations, despite the fact that some molecular alterations persist in the brain. This review reveals that animal models can be used to understand the mechanisms that underlie anxiety and depression in animals recovering from sepsis.

Keywords: Sepsis; animal models; anxiety; depression; long-term sequelae; psychiatric symptoms.

Fig. 1

Animal models of sepsis have been used in the study of the pathogenesis of neuropsychiatric disorders. LPS-induced systemic inflammation could be a useful tool to study anxiety and depressive symptoms in the context of sepsis. The CLP model consistently induces a depressive-like phenotype, making it an interesting model of the long-term mood disorders observed in human sepsis survivors. In both LPS and CLP models, basically the same molecular targets are altered: microglial activation and cytokines are frequently reported and generally affect the hippocampus; blood–brain barrier permeability is mentioned as one of the first mechanisms induced by the CLP model; besides this, oxidative stress, apoptosis, and HPA alterations are related