TY - JOUR
T1 - Role of glia in delirium
T2 - proposed mechanisms and translational implications
AU - Heffernan, Áine Bríd
AU - Steinruecke, Moritz
AU - Dempsey, Georgia
AU - Chandran, Siddharthan
AU - Selvaraj, Bhuvaneish T.
AU - Jiwaji, Zoeb
AU - Stavrou, Maria
N1 - Publisher Copyright:
© Crown 2024.
PY - 2024/10/27
Y1 - 2024/10/27
N2 - Delirium is a common acute onset neurological syndrome characterised by transient fluctuations in cognition. It affects over 20% of medical inpatients and 50% of those critically ill. Delirium is associated with morbidity and mortality, causes distress to patients and carers, and has significant socioeconomic costs in ageing populations. Despite its clinical significance, the pathophysiology of delirium is understudied, and many underlying cellular mechanisms remain unknown. There are currently no effective pharmacological treatments which directly target underlying disease processes. Although many studies focus on neuronal dysfunction in delirium, glial cells, primarily astrocytes, microglia, and oligodendrocytes, and their associated systems, are increasingly implicated in delirium pathophysiology. In this review, we discuss current evidence which implicates glial cells in delirium, including biomarker studies, post-mortem tissue analyses and pre-clinical models. In particular, we focus on how astrocyte pathology, including aberrant brain energy metabolism and glymphatic dysfunction, reactive microglia, blood-brain barrier impairment, and white matter changes may contribute to the pathogenesis of delirium. We also outline limitations in this body of work and the unique challenges faced in identifying causative mechanisms in delirium. Finally, we discuss how established neuroimaging and single-cell techniques may provide further mechanistic insight at pre-clinical and clinical levels.
AB - Delirium is a common acute onset neurological syndrome characterised by transient fluctuations in cognition. It affects over 20% of medical inpatients and 50% of those critically ill. Delirium is associated with morbidity and mortality, causes distress to patients and carers, and has significant socioeconomic costs in ageing populations. Despite its clinical significance, the pathophysiology of delirium is understudied, and many underlying cellular mechanisms remain unknown. There are currently no effective pharmacological treatments which directly target underlying disease processes. Although many studies focus on neuronal dysfunction in delirium, glial cells, primarily astrocytes, microglia, and oligodendrocytes, and their associated systems, are increasingly implicated in delirium pathophysiology. In this review, we discuss current evidence which implicates glial cells in delirium, including biomarker studies, post-mortem tissue analyses and pre-clinical models. In particular, we focus on how astrocyte pathology, including aberrant brain energy metabolism and glymphatic dysfunction, reactive microglia, blood-brain barrier impairment, and white matter changes may contribute to the pathogenesis of delirium. We also outline limitations in this body of work and the unique challenges faced in identifying causative mechanisms in delirium. Finally, we discuss how established neuroimaging and single-cell techniques may provide further mechanistic insight at pre-clinical and clinical levels.
UR - http://www.scopus.com/inward/record.url?scp=85207330081&partnerID=8YFLogxK
U2 - 10.1038/s41380-024-02801-4
DO - 10.1038/s41380-024-02801-4
M3 - Review article
AN - SCOPUS:85207330081
SN - 1359-4184
JO - Molecular Psychiatry
JF - Molecular Psychiatry
ER -