Ferroptosis in Traumatic Brain Injury: The Future Direction?

Abstract

Traumatic brain injury (TBI) is a severe acute brain injury caused by external mechanical force, resulting in temporary or permanent impairment of physical, psychological, cognitive functions, and altered consciousness states. Cognitive dysfunction commonly leading to symptoms such as inattention and decline in learning and memory abilities, and may also result in irritability, anxiety or depression. The underlying pathology involves significant neuron loss and limited synaptic remodeling. Abnormal iron metabolism is common in the brains of patients with TBI and cognitive impairment. However, effective intervention measures are still lacking which prompts us to explore new therapeutic targets and develop novel therapies for TBI. As a newly discovered form of regulated cell death, ferroptosis occurs due to excessive iron accumulation in the brain, leading to cellular and neuronal damage. Iron overload and ferroptosis play a significant role in the pathophysiology of secondary brain injury. Therefore, potential therapeutic approaches may involve targeting factors such as iron deposition and ferroptosis inhibition. This chapter provides an overview of ferroptosis’ role in traumatic brain injury (TBI) and advance investigation in related research fields with the aim of enhancing our understanding of TBI treatment through ferroptosis inhibition, ultimately guiding new clinical directions for further TBI research.