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Cerebral Response to Peripheral Challenge with a Viral Mimetic

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Abstract

It has been well established that peripheral inflammation resulting from microbial infections profoundly alters brain function. This review focuses on experimental systems that model cerebral effects of peripheral viral challenge. The most common models employ the induction of the acute phase response via intraperitoneal injection of a viral mimetic, polyinosinic-polycytidylic acid (PIC). The ensuing transient surge of blood-borne inflammatory mediators induces a “mirror” inflammatory response in the brain characterized by the upregulated expression of a plethora of genes encoding cytokines, chemokines and other inflammatory/stress proteins. These inflammatory mediators modify the activity of neuronal networks leading to a constellation of behavioral traits collectively categorized as the sickness behavior. Sickness behavior is an important protective response of the host that has evolved to enhance survival and limit the spread of infections within a population. However, a growing body of clinical data indicates that the activation of inflammatory pathways in the brain may constitute a serious comorbidity factor for neuropathological conditions. Such comorbidity has been demonstrated using the PIC paradigm in experimental models of Alzheimer’s disease, prion disease and seizures. Also, prenatal or perinatal PIC challenge has been shown to disrupt normal cerebral development of the offspring resulting in phenotypes consistent with neuropsychiatric disorders, such as schizophrenia and autism. Remarkably, recent studies indicate that mild peripheral PIC challenge may be neuroprotective in stroke. Altogether, the PIC challenge paradigm represents a unique heuristic model to elucidate the immune-to-brain communication pathways and to explore preventive strategies for neuropathological disorders.

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Acknowledgments

This work was partly supported by a research grant from the National Institutes of Health/National Institute of General Medical Sciences, U54GM104942. The content is solely the responsibility of the author and does not necessarily represent the official views of the NIH. The author would like to thank Mr. Brent Lally for proofreading this manuscript.

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  1. Department of Neurobiology and Anatomy, West Virginia University School of Medicine, 1 Medical Center Dr., Morgantown, WV, 26506-9128, USA

    Gregory Konat

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Konat, G. Cerebral Response to Peripheral Challenge with a Viral Mimetic. Neurochem Res 41, 144–155 (2016). https://doi.org/10.1007/s11064-015-1746-3

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