Role of glia in delirium: proposed mechanisms and translational implications.


Journal

Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835

Informations de publication

Date de publication:
27 Oct 2024
Historique:
received: 25 02 2024
accepted: 17 10 2024
revised: 23 08 2024
medline: 28 10 2024
pubmed: 28 10 2024
entrez: 28 10 2024
Statut: aheadofprint

Résumé

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.

Identifiants

pubmed: 39463449
doi: 10.1038/s41380-024-02801-4
pii: 10.1038/s41380-024-02801-4
doi:

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. Crown.

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Auteurs

Áine Bríd Heffernan (ÁB)

UK Dementia Research Institute at The University of Edinburgh, The University of Edinburgh, Edinburgh, UK.
Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK.

Moritz Steinruecke (M)

University of Cambridge School of Clinical Medicine, Cambridge, UK.

Georgia Dempsey (G)

School of Medicine, University of St Andrews, St Andrews, UK.
Centre for Neural Circuits and Behaviour, University of Oxford, Oxford, UK.

Siddharthan Chandran (S)

UK Dementia Research Institute at The University of Edinburgh, The University of Edinburgh, Edinburgh, UK.
Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK.
Euan MacDonald Centre for Motor Neuron Disease Research, The University of Edinburgh, Edinburgh, UK.
Anne Rowling Regenerative Neurology Clinic, The University of Edinburgh, Edinburgh, UK.

Bhuvaneish T Selvaraj (BT)

UK Dementia Research Institute at The University of Edinburgh, The University of Edinburgh, Edinburgh, UK.
Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK.
Euan MacDonald Centre for Motor Neuron Disease Research, The University of Edinburgh, Edinburgh, UK.
Anne Rowling Regenerative Neurology Clinic, The University of Edinburgh, Edinburgh, UK.

Zoeb Jiwaji (Z)

UK Dementia Research Institute at The University of Edinburgh, The University of Edinburgh, Edinburgh, UK.
Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK.

Maria Stavrou (M)

UK Dementia Research Institute at The University of Edinburgh, The University of Edinburgh, Edinburgh, UK. mstavrou@exseed.ed.ac.uk.
Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK. mstavrou@exseed.ed.ac.uk.
Euan MacDonald Centre for Motor Neuron Disease Research, The University of Edinburgh, Edinburgh, UK. mstavrou@exseed.ed.ac.uk.
Anne Rowling Regenerative Neurology Clinic, The University of Edinburgh, Edinburgh, UK. mstavrou@exseed.ed.ac.uk.

Classifications MeSH