Mitochondrial-Targeted Therapies in Traumatic Brain Injury: From Bench to Bedside

Authors

Sidra Tabassum
Silin Wu
Chang-Hun Lee
Bosco Seong Kyu Yang
Aaron M Gusdon
Huimahn A Choi
Xuefang S Ren

Publication Date

1-1-2025

Journal

Neurotherapeutics

Abstract

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide, with limited effective therapeutic options currently available. Recent research has highlighted the pivotal role of mitochondrial dysfunction in the pathophysiology of TBI, making mitochondria an attractive target for therapeutic intervention. This review comprehensively examines advancements in mitochondrial-targeted therapies for TBI, bridging the gap from basic research to clinical applications. We discuss the underlying mechanisms of mitochondrial damage in TBI, including oxidative stress, impaired bioenergetics, mitochondrial dynamics, and apoptotic pathways. Furthermore, we highlight the complex interplay between mitochondrial dysfunction, inflammation, and blood-brain barrier (BBB) integrity, elucidating how these interactions exacerbate injury and impede recovery. We also evaluate various preclinical studies exploring pharmacological agents, gene therapy, and novel drug delivery systems designed to protect and restore mitochondrial function. Clinical trials and their outcomes are assessed to evaluate the translational potential of mitochondrial-targeted therapies in TBI. By integrating findings from bench to bedside, this review emphasizes promising therapeutic avenues and addresses remaining challenges. It also provides guidance for future research to pave the way for innovative treatments that improve patient outcomes in TBI.

Keywords

Humans, Brain Injuries, Traumatic, Mitochondria, Animals, Translational Research, Biomedical, Genetic Therapy, Blood-Brain Barrier, Neuroprotective Agents, Drug Delivery Systems, Oxidative Stress, Traumatic brain injury, Mitochondrial dysfunction, Therapeutic interventions, Novel drug delivery system

DOI

10.1016/j.neurot.2024.e00515

PMID

39721917

PMCID

PMC11840356

PubMedCentral® Posted Date

12-24-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes