Mast Cells and Glia: Two Tracks on the Road to Neuroinflammation

Lecturer: Stephen Skaper, University of Padua, Padua, Italy.
 

One of the more important recent advances in neuroscience research is the understanding that there is extensive communication between the immune system and the central nervous system (CNS). Proinflammatory cytokines play a key role in this communication. The emerging realization is that glia and microglia, in particular, (which are the brain’s resident macrophages), constitute an important source of inflammatory mediators and may have fundamental roles in CNS disorders from neuropathic pain and epilepsy to neurodegenerative diseases. Microglia respond also to proinflammatory signals released from other non-neuronal cells, principally those of immune origin. Mast cells are of particular relevance in this context. These immune-related cells, while resident in the CNS, are capable of migrating across the blood-spinal cord and blood-brain barriers in situations where the barrier is compromised as a result of CNS pathology. Emerging evidence suggests the possibility of mast cell-glia communication and opens exciting new perspectives for designing therapies to target neuroinflammation by differentially modulating the activation of non-neuronal cells normally controlling neuronal sensitization, both peripherally and centrally. This presentation will provide an overview of recent progress relating to the pathobiology of neuroinflammation, the role of microglia, neuroimmune interactions involving mast cells, in particular, and the possibility that mast cell-microglia crosstalk may contribute to the exacerbation of acute symptoms of chronic neurodegenerative disease and accelerate disease progression, as well as promote pain transmission pathways.


 

Inflammation and Neurodegeneration in CNS Injury: Evolving Concepts and New Therapeutic Targets

Lecturer: Alan I. Faden, University of Maryland School of Medicine, Baltimore, MD.
 

It has long been claimed that prior traumatic brain injury (TBI) increases the subsequent incidence of Alzheimer’s disease (AD). However, recent larger epidemiological studies indicate a relationship to subsequent dementia but not to AD. There is also a well-recognized association between repeated mild TBI and progressive cognitive decline or other neuropsychiatric abnormalities. The latter was first described in boxers as dementia pugilistica, and has received widespread attention in relationship to high contact sports. The term chronic traumatic encephalopathy (CTE) has been used to define a “specific” entity marked by neurobehavioral changes and deposition of phosphorylated tau protein. Less well appreciated with regard to post-traumatic neurodegeneration is the role of sustained neuroinflammation, even though this association has been recognized pathologically for decades. More recent experimental work, as well as clinical neuroimaging studies, has underscored the relationship between chronic neuroinflammation and progressive brain neurodegeneration in a number of disorders including TBI, while providing mechanistic support. Manifested by extensive microglial and astroglial activation, chronic traumatic brain inflammation (CTBI), or perhaps better termed chronic traumatic inflammatory encephalopathy (CTIE), appears likely to be the most important cause of post-traumatic neurodegeneration and related cognitive decline in terms of prevalence. Perhaps even more critically, emerging preclinical studies indicate that persistent neuroinflammation and associated neurodegeneration may be treatable weeks to months after the initiating insult(s).