Advancing neuroprotection in traumatic brain injury: Maximizing the potential of the nuclear factor erythroid 2-related factor 2/nuclear factor kappa B pathway through insights from animal models

Abstract

Traumatic brain injury (TBI) is a primary public health concern that can result in significant long-term disability and mortality. Neuroprotection strategies that can mitigate the effects of TBI are urgently needed. The nuclear factor erythroid 2-related factor 2 (Nrf-2)/nuclear factor kappa B (NF-κB) pathway has emerged as a promising TBI neuroprotection target because it regulates inflammation, oxidative stress, and mitochondrial dysfunction. This review summarizes the current preclinical evidence supporting the role of the Nrf-2/NF-κB pathway in TBI and the mechanisms underlying its regulation. Pharmacological and genetic approaches have been used to modulate the pathway in animal models of TBI, resulting in improved functional, histological, and molecular outcomes. The molecular mechanisms underlying the Nrf-2/NF-κB pathway in TBI involve regulating inflammation, oxidative stress, and mitochondrial dysfunction. The future studies should focus on identifying safe and effective agents for modulating this pathway, optimizing dosing regimens, and exploring combination therapies targeting multiple TBI pathways. While preclinical studies have shown promising results, further research is needed to determine the safety and efficacy of modulating the Nrf-2/NF-κB pathway in human TBI patients. Overall, the Nrf-2/NF-κB pathway represents a promising target for neuroprotection in TBI, and further research is needed to translate these preclinical findings into effective treatments for human patients.