Fig. 1: Schematic outline of glial dysfunction in delirium and technologies which can be used to further our understanding of their roles in its pathogenesis.
From: Role of glia in delirium: proposed mechanisms and translational implications
Glial dysfunction has been described in delirium, but the underlying pathophysiological mechanisms are not fully understood. Key risk factors for and triggers of delirium include older age, pre-existing neurodegeneration, systemic inflammation, surgery, new medications and drug withdrawal. Reactive astrocytes with increased inflammasome activity, altered metabolism and impaired glymphatic activity have been reported in patients and models with delirium. Similarly, microglia display elevated cytokine production and C1q-tagged signalling. Impaired blood-brain barrier function and white matter changes have also been noted. Exploiting existing technologies including single-cell transcriptomics, neuroimaging, liquid biomarkers and optogenetics would provide deeper mechanistic insight into the roles of dysregulated glia in delirium. The effects of these mechanisms on neuronal function should also be interrogated. GFAP: glial fibrillary acidic protein; CXCL10: C-X-C motif chemokine ligand 10; IL-6/1β: interleukin-6/1β; TNFα: tumour necrosis factor α; C1q: complement component 1q; CD68: cluster of differentiation 68; TLR2: toll-like receptor 2.
