Diet’s Impact on Post-Traumatic Brain Injury Depression: Exploring Neurodegeneration, Chronic Blood–Brain Barrier Destruction, and Glutamate Neurotoxicity Mechanisms

Abstract

Traumatic brain injury (TBI) has a profound impact on cognitive and mental functioning, leading to lifelong impairment and significantly diminishing the quality of life for affected individuals. A healthy blood–brain barrier (BBB) plays a crucial role in guarding the brain against elevated levels of blood glutamate, making its permeability a vital aspect of glutamate regulation within the brain. Studies have shown the efficacy of reducing excess glutamate in the brain as a treatment for post-TBI depression, anxiety, and aggression. The purpose of this article is to evaluate the involvement of dietary glutamate in the development of depression after TBI. We performed a literature search to examine the effects of diets abundant in glutamate, which are common in Asian populations, when compared to diets low in glutamate, which are prevalent in Europe and America. We specifically explored these effects in the context of chronic BBB damage after TBI, which may initiate neurodegeneration and subsequently have an impact on depression through the mechanism of chronic glutamate neurotoxicity. A glutamate-rich diet leads to increased blood glutamate levels when contrasted with a glutamate-poor diet. Within the context of chronic BBB disruption, elevated blood glutamate levels translate to heightened brain glutamate concentrations, thereby intensifying neurodegeneration due to glutamate neurotoxicity.

The Relationship between Post-Traumatic Stress Disorder Due to Brain Injury and Glutamate Intake: A Systematic Review

“…Several factors can disrupt and cause the normally stable levels of blood glutamate concentrations to fluctuate. One of these factors may be dietary intake, caused by the presence of glutamate in many foods [ 33 ]. Traditional diets in Asian countries include high levels of glutamate because monosodium glutamate (MSG) is a popular flavoring in many cuisines, especially in East and Southeast Asian cuisine [ 103 , 104 ].…”

“…A recent related hypothesis points to the development of post-TBI neuropsychiatric sequelae through chronic blood–brain barrier (BBB) destruction, chronic glutamate neurotoxicity, and neurodegeneration [ 31 , 32 ]. In a previous investigation, we examined the effect of dietary glutamate on chronic neurotoxicity and its role in the development of post-TBI depression [ 33 ].…”

Association of Blood Metabolomics Biomarkers with Brain Metabolites and Patient-Reported Outcomes as a New Approach in Individualized Diagnosis of Schizophrenia

“…Disturbances in glutamatergic signaling have been associated with the pathogenesis of, among others, such mental disorders as schizophrenia, bipolar disorder, anxiety and depression [63]. Plasma glutamate concentration is associated with the severity of depression [64]. Luykx et al in their metaanalysis, draw attention to brain region-specific changes in depression that are dependent on glutamate level [65].…”

FMOD Alleviates Depression-Like Behaviors by Targeting the PI3K/AKT/mTOR Signaling After Traumatic Brain Injury

“…Depression is one of the most common psychiatric sequelae ensuing from TBI, it might influence 25–50% of TBI patients (Jahan & Tanev, 2023 ). Studies suggested that TBI-related depression significantly affected personal life quality and even resulted in lifelong impairment (Boyko et al, 2023 ). Nevertheless, much remains unclear about the complicated neurobiological alternations of post-TBI depression.…”