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.

Biomarkers of neuropsychiatric dysfunction in intensive care unit survivors: a prospective cohort study

“…At least in animal models, anxiety and depression are strongly associated events. ( 47 ) Chronic mild stress causes both anxiety and depression, is associated with long-term cognitive dysfunction, and potentiates the dysfunction observed in septic survivors. ( 48 , 49 ) It is believed that chronic stress and inflammation combine to compromise vascular and brain function.…”

Neuroinflammation in Sepsis: Molecular Pathways of Microglia Activation

“…Evidence shows that microglia have a role in regulating mood and affective disorders, including depression, among the long-term mental health disorders found in sepsis survivors [ 5 , 133 ]. Recent work has demonstrated that microglia activation in the striatum is associated with increased firing of striatal medium spiny neurons and induces depressive-like behavior in mice.…”

Skewing cPLA 2 α activity toward oxoeicosanoid production promotes neutrophil N2 polarization, wound healing, and the response to sepsis

“…The physiologic condition of sepsis is also initially characterized by a hyperinflammatory stage, as shown by the presence of fever, tachycardia, tachypnea, and altered leukocyte numbers along with a known site of infection ( 2 ). As with wound healing, neutrophil infiltration, in this case to the site of infection, is also required to clear pathogens and damaged tissue ( 3 ). Efferocytosis is also a key step in the septic response for eventual resolution and recovery ( 4 , 5 ).…”