Premedication with Doxycycline Attenuates Early and Delayed LPS-Induced Neuroinflammation in Rats

A systemic injection of lipopolysaccharide (LPS) induces a prolonged neuroinflammatory response, which is accompanied by microglial activation, neuronal damage, and movement disorders. The aim of this study was to evaluate the effect of a 14-day course of premedication with doxycycline (25 mg/kg) on the severity of neuroinflammation and its delayed effects in a rat model of LPS-induced systemic inflammation. A total of 80 male Wistar rats were used in two sequential experiments and allocated to 4 experimental groups: control, LPS, doxycycline, and doxycycline + LPS. Doxycycline was administered intragastrically according to the regimen mentioned above, while LPS was administered intraperitoneally once at a dose of 1 mg/kg on the 15th day of the experiment. Locomotor function was assessed using the Narrowing Beam Walking test, Foot Fault test, and Gait Analysis 30 and 60 days after LPS administration. 48 h and 60 days after LPS administration, a histological examination of the brain was performed, along with the analysis of TNF-α, IL-1β, iNOS, and IBA-1 mRNA expression in the hippocampus and prefrontal cortex using RT-qPCR. A single systemic administration of LPS induced early and delayed increases in inflammatory gene expression in brain structures, accompanied by motor impairments, morphological changes suggestive of glial activation, and reduced cellularity. Doxycycline premedication attenuated these molecular, behavioral, and morphological changes in rats. These findings support the anti-inflammatory and neuroprotective potential of doxycycline in this experimental model of systemic inflammation.