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Review
. 2024 May 7;25(10):5085.
doi: 10.3390/ijms25105085.

Chronic Stress-Induced Neuroinflammation: Relevance of Rodent Models to Human Disease

Abigail G White  1 , Elias Elias  1 , Andrea Orozco  2 , Shivon A Robinson  2 , Melissa T Manners  1
Affiliations
Review

Chronic Stress-Induced Neuroinflammation: Relevance of Rodent Models to Human Disease

Abigail G White et al. Int J Mol Sci. .

Abstract

The brain is the central organ of adaptation to stress because it perceives and determines threats that induce behavioral, physiological, and molecular responses. In humans, chronic stress manifests as an enduring consistent feeling of pressure and being overwhelmed for an extended duration. This can result in a persistent proinflammatory response in the peripheral and central nervous system (CNS), resulting in cellular, physiological, and behavioral effects. Compounding stressors may increase the risk of chronic-stress-induced inflammation, which can yield serious health consequences, including mental health disorders. This review summarizes the current knowledge surrounding the neuroinflammatory response in rodent models of chronic stress-a relationship that is continually being defined. Many studies investigating the effects of chronic stress on neuroinflammation in rodent models have identified significant changes in inflammatory modulators, including nuclear factor-κB (NF-κB) and toll-like receptors (TLRs), and cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6. This suggests that these are key inflammatory factors in the chronic stress response, which may contribute to the establishment of anxiety and depression-like symptoms. The behavioral and neurological effects of modulating inflammatory factors through gene knockdown (KD) and knockout (KO), and conventional and alternative medicine approaches, are discussed.

Keywords: CUMS; UCMS; behavior; chronic stress; cytokines; inflammation.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Reported inflammatory changes in brain regions and serum of rodent models of chronic stress. Following chronic stress, represented by the rodent outlined in red, the brain is dissected, serum is collected, and inflammatory factors and mediators are measured. Stress-induced inflammatory changes are reported in individual brain regions and serum. NF-κB = nuclear factor kappa-light-chain-enhancer of activated B cells, IL = interleukin, TLR = toll-like receptor, TNF-α = tumor necrosis factor-alpha, NLRP3 = NLR family pyrin domain containing 3, and IFN = interferons. Created with BioRender.com.
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