TY - JOUR
T1 - Glutamate Neurotoxicity and Destruction of the Blood-Brain Barrier
T2 - Key Pathways for the Development of Neuropsychiatric Consequences of TBI and Their Potential Treatment Strategies
AU - Gruenbaum, Benjamin F.
AU - Zlotnik, Alexander
AU - Fleidervish, Ilya
AU - Frenkel, Amit
AU - Boyko, Matthew
N1 - Funding Information:
This research was partly supported by the ISRAEL SCIENCE FOUNDATION (grant No. 1490/15) awarded to Matthew Boyko and Alexander Zlotnik.
Publisher Copyright:
© 2022 by the authors.
PY - 2022/8/25
Y1 - 2022/8/25
N2 - 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.
AB - 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.
KW - blood glutamate scavengers
KW - blood–brain barrier (BBB)
KW - glutamate
KW - neuropsychiatric conditions
KW - traumatic brain injury (TBI)
UR - http://www.scopus.com/inward/record.url?scp=85137569022&partnerID=8YFLogxK
U2 - 10.3390/ijms23179628
DO - 10.3390/ijms23179628
M3 - Review article
C2 - 36077024
AN - SCOPUS:85137569022
SN - 1661-6596
VL - 23
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 17
M1 - 9628
ER -