Bimodal effect of ketamine on neurotrophic factors and inflammatory parameters in cecal ligation and puncture-induced sepsis model

Abstract

Abstract Background: Studies have demonstrated an important impact of systemic inflammation in the central nervous system, which could be related to psychiatric disorders’ pathophysiology. Ketamine can have anti-inflammatory proprieties, but dose-dependently effects need to be studied. Objective: To evaluate the effect of different doses of ketamine on levels of neurotrophins and inflammatory cytokines in the brains of rats. Methods: Wistar rats were submitted to the cecal ligation and puncture (CLP) model of sepsis. Thirty days after the CLP procedure, the rats received an intraperitoneal injection (i.p.) of ketamine (5, 15, or 25 mg/kg) or saline, once a day for seven days. The rats were killed 30 minutes after the last i.p. injection. The frontal cortex, hippocampus, and striatum were dissected for analysis of IL-1𝛽, IL-6, IL-10, TNF-α, BDNF, NGF, NT-3, and GDNF levels. Results: CLP increased the levels of IL-1𝛽, IL-6, IL-10, and TNF-α levels in the frontal cortex and/or hippocampus of rats. Besides, BDNF levels were decreased by CLP in all structures analyzed. NGF and GDNF were decreased only in the hippocampus. Ketamine at 5 mg/kg reversed all alterations caused by CLP and per se increased the levels of BDNF and NGF in the frontal cortex and/or hippocampus. Ketamine at 15 mg/kg increased BDNF and NGF levels. In turn, Ketamine at 25mg/kg potentiates the inflammatory injury on the brain induced by CLP. Conclusion:We suggest that ketamine could work differently in a systemic inflammation environment, and caution needs to be taken depending on the inflammatory history of the patient.