Monitoring and Modulating Inflammation-Associated Alterations in Synaptic Plasticity: Role of Brain Stimulation and the Blood-Brain Interface.

Maximilian Lenz,Andreas Vlachos,Amelie Eichler

doi:10.3390/biom11030359

Abstract

Inflammation of the central nervous system can be triggered by endogenous and exogenous stimuli such as local or systemic infection, trauma, and stroke. In addition to neurodegeneration and cell death, alterations in physiological brain functions are often associated with neuroinflammation. Robust experimental evidence has demonstrated that inflammatory cytokines affect the ability of neurons to express plasticity. It has been well-established that inflammation-associated alterations in synaptic plasticity contribute to the development of neuropsychiatric symptoms. Nevertheless, diagnostic approaches and interventional strategies to restore inflammatory deficits in synaptic plasticity are limited. Here, we review recent findings on inflammation-associated alterations in synaptic plasticity and the potential role of the blood–brain interface, i.e., the blood–brain barrier, in modulating synaptic plasticity. Based on recent findings indicating that brain stimulation promotes plasticity and modulates vascular function, we argue that clinically employed non-invasive brain stimulation techniques, such as transcranial magnetic stimulation, could be used for monitoring and modulating inflammation-induced alterations in synaptic plasticity.

Highlights

Inflammatory processes aim at resolving tissue damage by facilitating repair and recovery mechanisms [1]
This hypothesis has been supported by research describing the effects of the bacterial endotoxin lipopolysaccharide (LPS) on synaptic plasticity: Several studies have shown that systemic administration of LPS promotes a substantial increase in brain
TNFα levels, which impairs synaptic plasticity [34,41,42,43,44]. Consistent with these findings, we have recently shown that application of LPS directly to cultured brain tissue triggers microglial TNFα expression and leads to alterations in synaptic plasticity [34]

Summary

Introduction

Inflammatory processes aim at resolving tissue damage by facilitating repair and recovery mechanisms [1]. While the precise mechanisms through which distinct TNFα levels affect microglia–astrocyte interactions and modulate synaptic plasticity have not yet been well characterized, it is conceivable that a pathological increase in brain TNFα levels—as seen under conditions of local or systemic inflammation—may induce dysregulation of synaptic transmission and plasticity This hypothesis has been supported by research describing the effects of the bacterial endotoxin lipopolysaccharide (LPS) on synaptic plasticity: Several studies have shown that systemic (intraperitoneal) administration of LPS promotes a substantial increase in brain. Systemic and local inflammation are expected to have a major impact on brain function by triggering immune responses that induce the expression of TNFα, IL1β, and other cytokines above physiological levels. It will be important to gain further insights on the neuronal targets and precise cellular and molecular downstream mechanisms through which inflammation affects synaptic plasticity and brain function (c.f., [31,40,47])

Restraining Inflammation Restores Alterations in Synaptic Plasticity

Non-Invasive Brain Stimulation as a Tool to Monitor and Potentially Modulate