Glutamate Neurotoxicity and Destruction of the Blood-Brain Barrier: Key Pathways for the Development of Neuropsychiatric Consequences of TBI and Their Potential Treatment Strategies

Benjamin F. Gruenbaum, Alexander Zlotnik, Ilya Fleidervish, Amit Frenkel, Matthew Boyko

Research output: Contribution to journalReview articlepeer-review

13 Scopus citations

Abstract

Traumatic brain injury (TBI) is associated with significant cognitive and psychiatric conditions. Neuropsychiatric symptoms can persist for years following brain injury, causing major disruptions in patients' lives. In this review, we examine the role of glutamate as an aftereffect of TBI that contributes to the development of neuropsychiatric conditions. We hypothesize that TBI causes long-term blood-brain barrier (BBB) dysfunction lasting many years and even decades. We propose that dysfunction in the BBB is the central factor that modulates increased glutamate after TBI and ultimately leads to neurodegenerative processes and subsequent manifestation of neuropsychiatric conditions. Here, we have identified factors that determine the upper and lower levels of glutamate concentration in the brain after TBI. Furthermore, we consider treatments of disruptions to BBB integrity, including repairing the BBB and controlling excess glutamate, as potential therapeutic modalities for the treatment of acute and chronic neuropsychiatric conditions and symptoms. By specifically focusing on the BBB, we hypothesize that restoring BBB integrity will alleviate neurotoxicity and related neurological sequelae.

Original languageEnglish
Article number9628
JournalInternational Journal of Molecular Sciences
Volume23
Issue number17
DOIs
StatePublished - 25 Aug 2022

Keywords

  • blood glutamate scavengers
  • blood–brain barrier (BBB)
  • glutamate
  • neuropsychiatric conditions
  • traumatic brain injury (TBI)

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Fingerprint

Dive into the research topics of 'Glutamate Neurotoxicity and Destruction of the Blood-Brain Barrier: Key Pathways for the Development of Neuropsychiatric Consequences of TBI and Their Potential Treatment Strategies'. Together they form a unique fingerprint.

Cite this