# The metabolic consequences of evoked spreading depolarization in brain slices

## TL;DR

This study explores how brain tissue metabolism changes during spreading depolarization and finds that glucose deprivation worsens recovery, but coenzyme Q10 may help.

## Contribution

The study reveals how spreading depolarization affects metabolism and shows coenzyme Q10 improves recovery under glucose deficiency.

## Key findings

- Spreading depolarization increases mitochondrial activity and shifts metabolism to anaerobic respiration and glycolysis.
- Glucose deprivation impairs recovery and disrupts central carbon metabolism.
- Coenzyme Q10 supplementation improves metabolic recovery in glucose-deprived brain slices.

## 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.