Pioglitazone restores mitochondrial function but does not spare cortical tissue following mild brain contusion

Brain Communications, 2023 · DOI: https://doi.org/10.1093/braincomms/fcad032 · Published: February 13, 2023

Simple Explanation

This study investigates the therapeutic effects of pioglitazone, a drug known to improve brain bioenergetics after traumatic brain injury (TBI), in a mild brain contusion model. The research focuses on how pioglitazone affects mitochondrial function in different brain regions (cortex and hippocampus) and mitochondrial subpopulations (total, glia-enriched, and synaptic mitochondria). Pioglitazone treatment was administered at various time points (0.25, 3, 12, or 24 hours) following a mild controlled cortical impact (CCI). The researchers then assessed mitochondrial respiration and oxidative damage in the brain tissues. The study found that early pioglitazone treatment (0.25 hours post-injury) could restore mitochondrial respiration in the cortex. However, delayed treatment did not improve cortical tissue sparing. These findings suggest that early intervention with pioglitazone can have beneficial effects on mitochondrial function after mild TBI.

Study Duration

Acute study: 48 hours; Subacute efficacy study: 15 days

Participants

Male C57BL/6J mice (2–3 months old), N = 4–8/group

Evidence Level

Not specified

Key Findings

1
Early pioglitazone treatment (0.25 h post-injury) restores maximal mitochondrial respiration in total and synaptic fractions of cortical mitochondria after mild controlled cortical impact.
2
Delayed pioglitazone treatment (3 h) increases maximal mitochondrial bioenergetics in synaptic hippocampal mitochondria compared to the vehicle-treated CCI group.
3
Pioglitazone treatment initiated at either 3 or 24 h after mild brain contusion does not improve spared cortical tissue at 15 days post-injury.

Research Summary

This study examined the effects of pioglitazone on mitochondrial function and cortical tissue sparing following mild brain contusion in mice. The researchers used a controlled cortical impact (CCI) model and administered pioglitazone at various time points after injury. The results showed that early pioglitazone treatment could restore mitochondrial respiration in the cortex, particularly in total and synaptic mitochondrial fractions. However, delayed pioglitazone treatment did not improve cortical tissue sparing. The findings suggest that early intervention with pioglitazone may be beneficial for restoring mitochondrial function after mild traumatic brain injury, but further investigation is needed to determine functional improvements beyond cortical tissue sparing.

Practical Implications

Therapeutic Timing

Early administration of pioglitazone is crucial for restoring mitochondrial function following mild TBI.

Targeted Therapy

Synaptic mitochondria are a key target for therapeutic interventions aimed at improving bioenergetics after brain injury.

Further Research

Further studies are needed to investigate the potential functional improvements of pioglitazone beyond cortical tissue sparing, such as network connectivity and neuronal function.

Study Limitations

1
The study only used male mice.
2
The study utilized an open skull model of CCI.
3
Further investigation is needed into improvements into network connectivity in the brain, neuronal function, and/or vascular health that pioglitazone provides after mild brain contusion.

Your Feedback

Was this summary helpful?

Back to Neurology