TABLE 2.
Brain dysfunction in mouse and rat sepsis models.
| Model | Region | Acute or chronic phase | Characteristics | Symptoms | References |
| Mouse (LPS model) | Hippocampus | Acute phase (after 6 h) | Microglial processes thickened and Iba1 staining increased. | Johansson et al., 2013 | |
| Mouse (LPS model) | Hippocampus | Acute phase (after 2 h) | mRNA of IL-1β increased. | Hypothermia after LPS or IL-1β administration. Locomotor activity was reduced after IL-6, IL-1β, and LPS administration. | Skelly et al., 2013 |
| Mouse (LPS model) | Hippocampus | Acute phase (after 6 h) | mRNA of IL-1β and IL-6 increased. | IL-1 receptor antagonist treatment decreased hippocampal microglia and improved cognitive function. | Terrando et al., 2010 |
| Mouse (LPS model) | Acute phase (3–9 h) | LPS treatment caused impaired memory retention. IL-1β antagonist treatment ameliorated cognitive dysfunction. | Skelly et al., 2019 | ||
| Mouse (LPS model) | Hippocampus | Chronic phase (after 7 and 63 days) | Excitatory synapses decreased by microglia. | Manabe et al., 2021 | |
| Mouse (LPS model) | Frontal cortex, hippocampus, cerebellum | Chronic phase (after 2 months) | LPS-treated mice showed sustained microglial activity and increased mRNA for IL-1β and TNF-α compared to NOS2 KO mice. | LPS-treated mice had cognitive deficits; LPS administration to NOS2 KO mice did No change in the cognitive deficits. | Weberpals et al., 2009 |
| Mouse (LPS model) | Hippocampus | Chronic phase (after 7 days) | BDNF inhibitor treatment improved memory impairment and LTP. | Hippensteel et al., 2019 | |
| Mouse (LPS model) | Hippocampus | Chronic phase (after 7 days) | Administration of sulindac sulfide suppressed amyloidogenesis and neuronal cell death. | Memory impairment caused by LPS. Memory impairment improved after treatment with sulindac sulfide. | Lee et al., 2008 |
| Mouse (LPS model) | Hippocampus | Acute phase | IL-1β treatment decreased membrane potential and induced apoptosis. | Skelly et al., 2019 | |
| Mouse (CLP model) | Hippocampus | Acute phase (after a few days) | Nox2 expression was inhibited after the administration of NADPH oxidase inhibitor. | Cognitive impairment was improved 15 days after NADPH oxidase inhibitor administration. | Hernandes et al., 2014 |
| Mouse (pneumonia model) | Frontal lobe | Acute phase (after 1 day) | Neutrophils adhered to the blood vessels in the frontal lobe. | Dementia after 14 days | Andonegui et al., 2018 |
| Mouse (influenza infection model) | Hippocampus | Chronic phase (after 30 days) | Dendritic density decreased. | Spatial memory formation was impaired. | Hosseini et al., 2018 |
| Mouse (IL-1R1 reporter mouse line) | Hippocampus | Acute phase (immediately after IL-1 administration) | Stimulation of hippocampal endothelial cells with IL-1 induced IL-1 from microglia. | Liu et al., 2019 | |
| Rat (LPS model) | Cortex, hippocampus | Acute phase (after 1 day) | Decreased brain glucose uptake in neocortical regions. Neuronal decrease in the cerebral cortex and hippocampus. | Semmler et al., 2008 | |
| Rat (LPS model) | Hippocampus, midbrain, cerebellum | Acute phase (after 24 h) | iNOS inhibitor treatment decreased apoptotic cells and Bcl-2 positive cells in the hippocampus. | Semmler et al., 2005 | |
| Rat (LPS model) | Hypothalamus, hippocampus | Acute phase (2 h) | IL-1 mRNA, protein expression increased. | Hosoi et al., 2000 | |
| Rat (CLP model) | Prefrontal cortex, hippocampus, striatum | Acute phase (after 24 h) | Treatment with IL-1β receptor antagonist improved BBB permeability and suppressed elevated IL-1β, TNF-α, and IL-6 levels. | IL-1β receptor antagonist treatment improved cognitive dysfunction after 10 days. | Mina et al., 2014 |
| Rat (CLP model) | Hippocampus | Chronic phase (after 10 days) | Minocycline treatment reduced cytokine levels and BBB breakdown in the hippocampus. | Michels et al., 2015 | |
| Rat (intraperitoneal injection of E-coli) | Hippocampus | Chronic phase | Aging rats had elevated IL-1 protein levels in the hippocampus compared to young rats. | Barrientos et al., 2006 |
LPS, lipopolysaccharide; Iba1, ionized calcium-binding adapter molecule 1; IL-1β, interleukin-1β; TNF, tumor necrosis factor; NOS2 KO mice, nitric oxide synthase 2 knockout mice; BDNF, brain-derived neurotrophic factor; LTP, long-term potentiation; CLP, cecal ligation and puncture; BBB, blood-brain barrier.