‘Neuroinflammation’ differs categorically from inflammation: transcriptomes of Alzheimer's disease, Parkinson's disease, schizophrenia and inflammatory diseases compared

Abstract

'Neuroinflammation' has become a widely applied term in the basic and clinical neurosciences but there is no generally accepted neuropathological tissue correlate. Inflammation, which is characterized by the presence of perivascular infiltrates of cells of the adaptive immune system, is indeed seen in the central nervous system (CNS) under certain conditions. Authors who refer to microglial activation as neuroinflammation confuse this issue because autoimmune neuroinflammation serves as a synonym for multiple sclerosis, the prototypical inflammatory disease of the CNS. We have asked the question whether a data-driven, unbiased in silico approach may help to clarify the nomenclatorial confusion. Specifically, we have examined whether unsupervised analysis of microarray data obtained from human cerebral cortex of Alzheimer's, Parkinson's and schizophrenia patients would reveal a degree of relatedness between these diseases and recognized inflammatory conditions including multiple sclerosis. Our results using two different data analysis methods provide strong evidence against this hypothesis demonstrating that very different sets of genes are involved. Consequently, the designations inflammation and neuroinflammation are not interchangeable. They represent different categories not only at the histophenotypic but also at the transcriptomic level. Therefore, non-autoimmune neuroinflammation remains a term in need of definition.

Role of neuroinflammation in ischemic stroke

“…[43] The neuroinflammation process is decided by the scene, duration and course of the neurological insult. [44] Neuroinflammation can perform function that are either supportive or destructive by which is determined by the immune signals relayed to the CNS. The nature of neuroinflammatory function can depend on the conditions and the intensity and duration of inflammation.…”

Temporal profile of M1 and M2 responses in the hippocampus following early 24 h of neurotrauma

“…The process involves many pro-inflammatory and antiinflammatory factors derived from both blood infiltrates and local cells [72]. Although a precise definition for inflammation in the brain is still unclear [29], but, it is well known that inflammation plays essential roles in the neuropathological conditions and is associated with cognitive impairment [2,86,89,90].…”

“…Activated microglia become a source of cytokines/chemokines [33,65] and other reactive components [16] that lead to SIC [59,66] as well as participating in the repair/recovery processes [3,14,39,70]. Such inflammation in the CNS is also referred as neuroinflammation [59], however, it is difficult to explain how glial activation manages the corresponding complex cell signal mechanisms in both neurons and the immune systems [20,29]. Glial activation contributes to immunological functions [38], synaptic turnover [14,66,70,79], and recovery processes after CNS injury [3,39].…”

Mitochondrial dysfunction and damage associated molecular patterns (DAMPs) in chronic inflammatory diseases

“…Furthermore, neuroinflammation has been difficult to define its pathogenic roles in relation to most neurodegenerative diseases (Ransohoff, 2016). Thus, it should be noted that the designations inflammation and neuroinflammation are not interchangeable and the term, ‘neuroinflammation,’ should be carefully and specifically applied (Filiou et al, 2014; Masgrau et al, 2017). …”