Behavioral deficits in sepsis-surviving rats induced by cecal ligation and perforation

Abstract

Sepsis and its complications are the leading causes of mortality in intensive care units, accounting for 10-50% of deaths. Intensive care unit survivors present long-term cognitive impairment, including alterations in memory, attention, concentration, and/or global loss of cognitive function. In the present study, we investigated behavioral alterations in sepsis-surviving rats. One hundred and ten male Wistar rats (3-4 months, 250-300 g) were submitted to cecal ligation and puncture (CLP), and 44 were submitted to sham operation. Forty-four rats (40%) survived after CLP, and all sham-operated animals survived and were used as control. Twenty animals of each group were used in the object recognition task (10 in short-term memory and 10 in long-term memory), 12 in the plus-maze test and 12 in the forced swimming test. Ten days after surgery, the animals were submitted individually to an object recognition task, plus-maze and forced swimming tests. A significant impairment of short-and long-term recognition memory was observed in the sepsis group (recognition index 0.75 vs 0.55 and 0.74 vs 0.51 for short-and long-term memory, respectively (P < 0.05). In the elevated plus-maze test no difference was observed between groups in any of the parameters assessed. In addition, sepsis survivors presented an increase in immobility time in the forced swimming test (180 vs 233 s, P < 0.05), suggesting the presence of depressive-like symptoms in these animals after recovery from sepsis. The present results demonstrated that rats surviving exposure to CLP, a classical sepsis model, presented recognition memory impairment and depressive-like symptoms but not anxietylike behavior.

Increased Oxidative Stress and Imbalance in Antioxidant Enzymes in the Brains of Alloxan-Induced Diabetic Rats

“…At the end of the study, rats with glycemia between 400 and 600 mg/dL were considered diabetic [20]. Fifteen days after the induction of diabetes, based in previous studies [21], all rats were submitted to the object recognition task, after which the animals were killed by decapitation and a biochemical analysis was undertaken of the brain tissues.…”

“…Between trials, the objects were washed with 10% ethanol solution. Exploration was defined as sniffing (exploring the object 3–5 cm away from it) or touching the object with the nose and/or forepaws [21]. …”

Memory deficits in males and females long after subchronic immune challenge

“…Previous work has demonstrated the long-lasting consequences of an overwhelming immune challenge on neural and cognitive function and for neuroimmune signaling. The cecal ligation and puncture model of sepsis results in impairments of memory that emerge soon after surgery (e.g., Barichello et al, 2007) and persist for months (e.g., Huerta et al, 2016). Similarly, a single high-dose injection of lipopolysaccharide results in memory deficits at least 5 months post-injection (Ming, Sawicki, & Bekar, 2015).…”

Receptor for advanced glycation end products mediates sepsis-triggered amyloid-β accumulation, Tau phosphorylation, and cognitive impairment

“…Therefore, the levels of pro-inflammatory markers, A␤, phosphorylated Tau, and RAGE-associated molecules (including RAGE, several RAGE ligands, and intracellular downstream targets) were monitored in serum and brain from 24 h to 30 days after CLP surgery. The serum was evaluated for peripheral inflammatory markers and RAGE ligands, and the hippocampus and prefrontal cortex were evaluated because these structures are directly associated with cognitive dysfunctions observed in this rat model (6,33). RAGE signaling was blocked by immune neutralization in the hippocampus between 15 and 19 days after CLP, and the cognitive function (inhibitory avoidance and object recognition tasks), neuroinflammatory (RAGE, Iba-1, and GFAP), and neurodegenerative markers (A␤ and phosphorylated Tau) were evaluated 30 -31 days after CLP.…”