Effects of systemic administration of ibuprofen on stress response in a rat model of post-traumatic stress disorder

Abstract

Pro-inflammatory cytokine and brain-derived neurotrophic factor (BDNF) are modulated in post-traumatic stress disorder (PTSD). This study investigated the effects of ibuprofen (IBU) on enhanced anxiety in a rat model of PTSD induced by a single prolonged stress (SPS) procedure. The effects of IBU on inflammation and BDNF modulation in the hippocampus and the mechanisms underlying for anxiolytic action of IBU were also investigated. Male Sprague-Dawley rats were given IBU (20 or 40 mg/kg, i.p., once daily) for 14 days. Daily IBU (40 mg/kg) administration signifi cantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index in the EPM test, and increased the time spent in the center of an open fi eld after SPS. IBU administration signifi cantly decreased the expression of pro-inflammatory mediators, such as tumor necrosis factor-α, interleukin-1β, and BDNF, in the hippocampus, as assessed by reverse transcription-polymerase chain reaction analysis and immunohistochemistry. These fi ndings suggest that IBU exerts a therapeutic effect on PTSD that might be at least partially mediated by alleviation of anxiety symptoms due to its anti-inflammatory activity and BDNF expression in the rat brain.

A SYSTEMATIC REVIEW OF TUMOR NECROSIS FACTOR-α IN POST-TRAUMATIC STRESS DISORDER: EVIDENCE FROM HUMAN AND ANIMAL STUDIES

“…Taken together, these findings suggest a potential pathophysiological role of hippocampal TNF-production in the development of PTSD. Interestingly, when the stressed rats were administered medication with antiinflammatory properties, the elevated TNF-concentration reduced to the level of non-stressed rats (Levkowitz et al 2015, Lee et al 2016). Furthermore, this coincided with a reduction of anxiety-like behaviours in the treated rats (but not in the stressed non-treated rats) which returned to a similar level to that seen in the non-stressed rats.…”

“…The results of these studies are presented in Table 1. Lee et al (2016) induced anxiety using a single prolonged stress (SPS) procedure and found elevated TNF-levels in the hippocampus of stressed rats, as compared to nonstressed rats. In contrast, stressed rats who received ibuprofen did not display elevated TNF-expression; these levels did not significantly differ from nonstressed rats.…”

“…Two of the studies measured TNF-levels (Levkovitz et al 2015, Liu et al 2016) and one assessed TNF-mRNA (Lee et al 2016) in the hippocampus of stressed rats. The results of these studies are presented in Table 1.…”

Immune signaling mechanisms of PTSD risk and symptom development: insights from animal models

“…Predator stress involves exposure to a predator, either protected, or under supervision with direct contact. Two studies associated SPS-induced anxiety-like behaviors and neuroinflammation, specifically increasing hippocampal IL-6, IL-1β and TNF-α expression 2 weeks after exposure [5,22,23]. Less is known about the long-term effects of a single predator stress on inflammation.…”

“…Because recruitment of macrophages to the brain and subsequent microglial activation might be mechanisms underlying the development of anxiety-like symptoms in vivo [32,33,35], minocycline might have neuroprotective effects through direct microglial inhibition [49]. Additionally, the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen, chronically administered for 2 weeks following stress, normalizes anxiety-like behavior and TNF-α and IL-1β hippocampal expression in the SPS model [23]. These studies indicate that anti-inflammatory drugs might be potential preventive treatments in PTSD, and that a pharmacological intervention within the first hours after a traumatic event might be sufficient to prevent the onset of the full spectrum of PTSD symptoms.…”