The metabolic consequences of evoked spreading depolarization in brain slices
Grech, Olivia Mugo, Caroline Hill, Lisa J Heaselgrave, Samuel R Alimajstorovic, Zerin Yiangou, Andreas Lyons, Hannah S Mitchell, James Lavery, Gareth G Fulton, Daniel
Grech, Olivia
Mugo, Caroline
Hill, Lisa J
Heaselgrave, Samuel R
Alimajstorovic, Zerin
Yiangou, Andreas
Lyons, Hannah S
Mitchell, James
Lavery, Gareth G
Fulton, Daniel
Abstract
Spreading depolarization is a wave of neuronal and glial depolarization that propagates through brain tissue, triggering neuropeptide release and altered blood flow. It has been observed in ischemic stroke, traumatic brain injury, subarachnoid haemorrhage, epilepsy, and migraine aura. Spreading depolarization imposes a high energetic demand, and recovery impaired under metabolic substrate deficiency. Despite its clinical relevance, metabolic responses remain poorly understood, limiting therapeutic progress. We investigated metabolic effects of spreading depolarisation using an ex vivo brain slice model, aiming to characterise changes in intracellular calcium signalling, mitochondrial function, and central carbon metabolism, and to assess the impact of glucose deprivation. We further tested whether coenzyme Q10 could improve recovery under metabolically compromised conditions. Spreading depolarization increased mitochondrial activity and shifted metabolism toward anaerobic respiration and glycolysis. Glucose deprivation impaired recovery, inducing mitochondrial dysfunction and accumulation intermediates indicative of tricarboxylic acid cycle stalling and disrupted central carbon metabolism. Supplementing glucose-deprived brain slices with coenzyme Q10 shortened spreading depolarization repolarization duration, indicating enhanced metabolic recovery. These findings demonstrate that spreading depolarization imposes a significant metabolic burden, particularly under glucose limitation, and that mitochondrial-targeted interventions such as coenzyme Q10 may enhance tissue resilience in neurological disorders.
MIDER Authors
Date
2026-02-11
Type
Article
Subject
Metabolism, Stroke, Subarachnoid haemorrhage, Epilepsy, Glucose
Collections
Citation
Grech O, Mugo C, Hill LJ, Heaselgrave SR, Alimajstorovic Z, Yiangou A, Lyons HS, Mitchell J, Lavery GG, Fulton D, Sinclair AJ. The metabolic consequences of evoked spreading depolarization in brain slices. Sci Rep. 2026 Feb 11;16(1):8389. doi: 10.1038/s41598-026-37175-w.
Journal / Source Title
Scientific Reports
DOI
10.1038/s41598-026-37175-w
PMID
41673123
Publisher
Nature Publishing Group
Publisher’s URL
https://www.nature.com/srep/