Exploring the Different Impacts of Ketamine on Neurotrophic Factors and Inflammatory Parameters in a Cecal Ligation and Puncture-Induced Sepsis Model

Overview

Journal Neurotox Res

Publisher Springer

Date 2025 Jan 20

PMID 39833594

Authors

Jorge M Aguiar-Geraldo

Lara Canever

Debora P Marino

Camila Coan

Taise Possamai-Della

Bruna Pescador

Joao Quevedo

Felipe Dal-Pizzol

Samira S Valvassori

Alexandra Ioppi Zugno

Affiliations

Soon will be listed here.

Abstract

Given ketamine's conflicting impacts on the central nervous system, investigating its effects within an inflammatory context becomes crucial. This study aimed to assess the impact of varying ketamine doses on neurotrophin and inflammatory cytokine levels within the brains of rats submitted to the sepsis model. Wistar rats were submitted to the cecal ligation and puncture (CLP) model of sepsis. Intraperitoneal ketamine injections (5, 15, or 25 mg/kg) or saline were administered daily for seven days, thirty days post-CLP. Rats were euthanized thirty minutes following the last injection for analysis of IL-1β, IL-6, IL-10, TNF-α, BDNF, NGF, NT-3, and GDNF levels in the frontal cortex, hippocampus, and striatum. CLP-induced elevated IL-1????, IL-6, IL-10, and TNF-α levels in the frontal cortex and hippocampus of rats, with reduced BDNF levels across all structures examined. Furthermore, reduced NGF and GDNF levels were observed solely in the hippocampus. Ketamine at 5 mg/kg normalized CLP-induced alterations and, in Sham animals, increased BDNF and NGF levels in the frontal cortex and/or hippocampus. At 15 mg/kg, ketamine elevated BDNF and NGF levels in Sham animals, while at 25 mg/kg, it exacerbated the inflammatory response initiated by CLP. These findings suggest variable effects of ketamine within a context of systemic inflammation, emphasizing the importance of considering individual inflammatory backgrounds when utilizing ketamine.

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