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.