Inflammasomes link vascular disease with neuroinflammation and brain disorders

Abstract

The role of inflammation in neurological disorders is increasingly recognised. Inflammatory processes are associated with the aetiology and clinical progression of migraine, psychiatric conditions, epilepsy, cerebrovascular diseases, dementia and neurodegeneration, such as seen in Alzheimer's or Parkinson's disease. Both central and systemic inflammatory actions have been linked with the development of brain diseases, suggesting that complex neuro-immune interactions could contribute to pathological changes in the brain across multiple temporal and spatial scales. However, the mechanisms through which inflammation impacts on neurological disease are improperly defined. To develop effective therapeutic approaches, it is imperative to understand how detrimental inflammatory processes could be blocked selectively, or controlled for prolonged periods, without compromising essential immune defence mechanisms. Increasing evidence indicates that common risk factors for brain disorders, such as atherosclerosis, diabetes, hypertension, obesity or infection involve the activation of NLRP3, NLRP1, NLRC4 or AIM2 inflammasomes, which are also associated with various neurological diseases. This review focuses on the mechanisms whereby inflammasomes, which integrate diverse inflammatory signals in response to pathogen-driven stimuli, tissue injury or metabolic alterations in multiple cell types and different organs of the body, could functionally link vascular- and neurological diseases and hence represent a promising therapeutic target.

Magnetic Resonance Imaging of Cardiovascular Function and the Brain

“…3–6 In addition, neurodegenerative disease and dementia may also be associated with activated systemic inflammation in diabetes mellitus, hyperlipidemia, atherosclerosis, hypertension, obesity, metabolic syndrome and infection, presumably by inducing vascular changes and activation of microglia cells in the brain. 7 …”

Pattern recognition receptors and inflammasome activation in the blood-brain barrier

“…In this scenario, the BBB is not only a passive part of the neuroinflammatory processes. Besides immune cells and resident cells with well-characterized immune functions, cellular components of the BBB like CECs and brain vascular pericytes can be involved in inflammatory responses (Lénárt et al, 2016;Navarro et al, 2016a). In these cells innate immune mechanisms are launched during the initial phase of neuroinflammation.…”

“…Increasing evidence suggests that besides immune cells, cells of the NVU can also express and activate PRRs and inflammasomes. Recent research has revealed that astrocytes and neurons express several TLRs (Lee et al, 2013) and NLRs, and they are able to activate inflammasomes in various neurological diseases (Lénárt et al, 2016). However, there is only few data about the expression and activity of PRRs and inflammasomes in CECs and brain pericytes and their role in neuroinflammation.…”

“…), the immune response being more detrimental than beneficial in the majority of the cases. In inflammatory processes of the brain infiltrating immune cells and almost all cells of the CNS (microglial cells, astrocytes, neurons and CECs) may take part (Lénárt et al, 2016). It is well known that among cells of the BBB, astrocytes are able to assemble inflammasomes.…”

“…It is well known that among cells of the BBB, astrocytes are able to assemble inflammasomes. They can activate NLRP1, NLRP3, NLRC4, AIM2 and possibly NLRP2 inflammasomes, which may play role in several P a g e | 44 neurodegenerative diseases (Lénárt et al, 2016). However, possible inflammasome activation in CECs and brain pericytes has not been tested so far.…”