Neuroinflammation disorders exacerbated by environmental stressors

Abstract

Neuroinflammation is a condition characterized by the elaboration of proinflammatory mediators within the central nervous system. Neuroinflammation has emerged as a dominant theme in contemporary neuroscience due to its association with neurodegenerative disease states such as Alzheimer's disease, Parkinson's disease and Huntington's disease. While neuroinflammation often is associated with damage to the CNS, it also can occur in the absence of neurodegeneration, e.g., in association with systemic infection. The "acute phase" inflammatory response to tissue injury or infections instigates neuroinflammation-driven "sickness behavior," i.e. a constellation of symptoms characterized by loss of appetite, fever, muscle pain, fatigue and cognitive problems. Typically, sickness behavior accompanies an inflammatory response that resolves quickly and serves to restore the body to homeostasis. However, recurring and sometimes chronic sickness behavior disorders can occur in the absence of an underlying cause or attendant neuropathology. Here, we review myalgic enchepalomyelitis/chronic fatigue syndrome (ME/CFS), Gulf War Illness (GWI), and chemobrain as examples of such disorders and propose that they can be exacerbated and perhaps initiated by a variety of environmental stressors. Diverse environmental stressors may disrupt the hypothalamic pituitary adrenal (HPA) axis and contribute to the degree and duration of a variety of neuroinflammation-driven diseases.

Keywords: Chemobrain “sickness behavior” stressors; GWI; ME/CFS; Neuroimmune; Neuroinflammation.

Figure 1:

Neuroinflammation continuum. Neuroinflammation occurs in a continuum. It can result from acute phase injury where recovery to baseline occurs quickly after minor traumatic injury or infections, but when neuroinflammation is sustained, it has widely been associated with neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and multiple sclerosis (MS). In the middle of this neuroinflammation continuum are chronic sickness behavior disorders with no apparent underlying neurodegeneration (ME/CFS, GWI and chemobrain represent examples of distinct diseases in this non‐neurodegenerative category).