Inflammation in Neurological Disorders: The Thin Boundary Between Brain and Periphery

Accumulating evidence suggests that inflammation is a major contributor in the pathogenesis of several highly prevalent, but also rare, neurological diseases. In particular, the neurodegenerative processes of Alzheimer's disease (AD), vascular dementia (VAD), Parkinson's disease (PD), and multiple sclerosis (MS) are fueled by neuroinflammation, which, in turn, is accompanied by a parallel systemic immune dysregulation. This cross-talk between periphery and the brain becomes substantial when the blood-brain barrier loses its integrity, as often occurs in the course of these diseases. It has been hypothesized that the perpetual bidirectional flux of inflammatory mediators is not a mere "static" collateral effect of the neurodegeneration, but represents a proactive phenomenon sparking and driving the neuropathological processes. However, the upstream/downstream relationship between inflammatory events and neurological pathology is still unclear. Solid recent evidence clearly suggests that metabolic factors, systemic infections, Microbiota dysbiosis, and oxidative stress are implicated, although to a different extent, in the development in brain diseases. Here, we reviewed the most solid published evidence supporting the implication of the axis systemic inflammation-neuroinflammation-neurodegeneration in the pathogenesis of AD, VAD, PD, and MS, highlighting the possible cause of the putative downstream component of the axis. Reaching a definitive clinical/epidemiological appreciation of the etiopathogenic significance of the connection between peripheral and brain inflammation in neurologic disorders is pivotal since it could open novel therapeutic avenues for these diseases.