Depressive-Like Parameters in Sepsis Survivor Rats

Abstract

The inflammatory and immune responses evoked in sepsis may create not only an acute brain dysfunction, which occurs in the majority of septic patients, but also long-term deficits such as memory impairment. In this context, we evaluated depressive-like parameters in sepsis survivor rats. For this purpose, male Wistar rats, weighing 300-350 g, underwent cecal ligation and perforation (CLP) (sepsis group) followed by "basic support", or were sham-operated (control group). After 3 days of the sepsis procedure, the animals were treated with imipramine at 10 mg/kg or saline during 14 days (days 3-17). The consumption of sweet food was measured for 7 days (days 10-17) and the body weight was measured before CLP, 10, and 17 days after CLP. Seventeen days after sepsis (immediately after sweet food consumption measurement), the animals were anesthetized and blood was withdrawn for the analyses of corticosterone and adrenocorticotropic hormone (ACTH) levels, and immediately killed by decapitation. The adrenal gland and hippocampus were immediately isolated and weighed, and the hippocampus was utilized for determining brain-derived neurotrophic factor (BDNF) levels. It was observed that animals subjected to CLP presented decreased sucrose intake. Septic rats did not increase body weight and presented an increase in the weight of adrenal gland. Both corticosterone and ACTH levels were increased, while hippocampus weight and BDNF levels in the hippocampus decreased. The treatment with imipramine reversed all the parameters described above. Our results supported the hypothesis that rats that survive sepsis show depressive-like behavior, alterations in the hypothalamus-pituitary-adrenal axis, and decreased BDNF levels in the hippocampus.

Correlation of Acute Phase Inflammatory and Oxidative Markers With Long-term Cognitive Impairment in Sepsis Survivors Rats

“…In this context, even past stressors can be associated with inflammation and lower BDNF levels (21,27), suggesting that sepsis can act as a stressor affecting BDNF levels and inducing long-term consequences for brain function. This is reinforced by the fact that we had previously demonstrated sustained activation of hypothalamic-pituitary-adrenal axis, lower hipoccampal size, and lower brain BDNF levels in septic animals (11). In addition, low doses of dexamethasone reverse long-term cognitive impairments in septic animals (28).…”

“…In addition, there is a sustained decrease in the levels of brain-derived neurotropic factor (BDNF) in the CNS, an activation of the hypothalamic-pituitary-adrenal axis, and a decrease in the weight of hippocampus (11). Despite this, there is no information on a direct relation between acute levels of brain inflammation and oxidative damage and the occurrence of long-term cognitive deficits.…”

Effects of Caffeine on Behavioural and Cognitive Deficits in Rats

“…Comim et al . also evaluated the parameters suggestive of depression in sepsis survivor rats. Therein, after the third day of surgery, the animals were treated with imipramine (10 mg/kg) for 14 days.…”

Imipramine reverses depressive-like parameters in pneumococcal meningitis survivor rats

“…The inoculation of lipopolysaccharide in an animal model induced the production of inflammatory mediators, like, TNF-a and interferon c acting on the anterior pituitary, particularly stimulating the synthesis and release into the ACTH circulation (Rettori et al 1994), resulting in the release of adrenal steroid, thus, increasing the corticosterone levels (Gallily et al 1997). Comim et al (2010) showed that the use of imipramine reversed depressive-like symptoms, ACTH and cortisol levels in survivor animals of the sepsis. We also found increased ACTH level in rats that survived from pneumococcal meningitis.…”

“…Imipramine was dissolved in saline immediately before the intraperitoneal injections. All treatments were administered in a volume of 1 mL/kg (Comim et al 2010).…”