Time-dependent behavioral recovery after sepsis in rats

Objective: To evaluate the cognitive performance in rats that survived sepsis induced by cecal ligation and puncture (CLP) after 10, 30 and 60 days. Design: Prospective, controlled experiment. Setting: Animal basic science laboratory. Subjects: Male Wistar rats, weighing 300-350 g. Interventions: The rats were sham-operated or submitted to CLP (sepsis group) with "basic support" (saline, s.c. at 50 mL/kg immediately and 12 h after CLP plus ceftriaxone, s.c. at 30 mg/kg and clindamycin, s.c. at 25 mg/kg 6, 12 and 18 h after CLP). Measurements and main results: The animals underwent six behavioral tasks 10, 30 and 60 days after surgery: (a) habituation to the open field; (b) inhibitory avoidance task; (c) continuous multiple trials step-down inhibitory avoidance task; (d) object recognition; (e) elevated plus-maze; and (f) forced swimming test. We demonstrated that survivors 10 days after CLP presented deficits on the habituation to the open field, step-down inhibitory avoidance, continuous multiple-trials step-down inhibitory avoidance, object recognition and forced swimming. After 30 days of sepsis induction, survivors maintained deficits on the step-down inhibitory avoidance, continuous multiple-trials step-down inhibitory avoidance and forced swimming. However, after 60 days all behavior deficits were reversed. Conclusions: These results indicate that the impairment of memory and learning, demonstrated 10 days after the induction of sepsis, persist 30 days after the CLP. The cognitive impairments did not persist after 60 days suggesting that this model can help in the understanding of the biological mechanisms associated with sepsis-induced sickness behavior.