Interactions of Glutamate and Gamma Amino Butyric Acid with the insulin-like growth factor system in traumatic brain injury (TBI) and/or cardiovascular accidents (CVA or stroke): A systematic review
T.I. Morales,
K.A. Stearns-Yoder,
A.S. Hoffberg,
T.K. Khan,
H. Wortzel,
L.A. Brenner
Affiliations
T.I. Morales
VA Rocky Mountain Mental Illness Research, Education and Clinical Center, University of Colorado, Anschutz School of Medicine, United States; Department of Physical Medicine and Rehabilitation, University of Colorado, Anschutz School of Medicine, United States; Corresponding author.
K.A. Stearns-Yoder
VA Rocky Mountain Mental Illness Research, Education and Clinical Center, University of Colorado, Anschutz School of Medicine, United States; Department of Physical Medicine and Rehabilitation, University of Colorado, Anschutz School of Medicine, United States
A.S. Hoffberg
VA Rocky Mountain Mental Illness Research, Education and Clinical Center, University of Colorado, Anschutz School of Medicine, United States
T.K. Khan
VA Rocky Mountain Mental Illness Research, Education and Clinical Center, University of Colorado, Anschutz School of Medicine, United States
H. Wortzel
VA Rocky Mountain Mental Illness Research, Education and Clinical Center, University of Colorado, Anschutz School of Medicine, United States; Department of Physical Medicine and Rehabilitation, University of Colorado, Anschutz School of Medicine, United States; Department of Neurology, University of Colorado, Anschutz School of Medicine, United States; Department of Psychiatry, University of Colorado, Anschutz School of Medicine, United States
L.A. Brenner
VA Rocky Mountain Mental Illness Research, Education and Clinical Center, University of Colorado, Anschutz School of Medicine, United States; Department of Physical Medicine and Rehabilitation, University of Colorado, Anschutz School of Medicine, United States; Department of Neurology, University of Colorado, Anschutz School of Medicine, United States; Department of Psychiatry, University of Colorado, Anschutz School of Medicine, United States
The brain maintains homeostasis of neural excitation in part through the receptor-mediated signaling of Glutamate (Glu) and Gamma Amino Butyric Acid (GABA), but localized injuries cause cellular release of excess Glu leading to neurotoxicity. The literature strongly supports the role of Insulin-like growth factor-1 (IGF-1) in adult brain neuroprotection and repair, and research supporting the existence of molecular interactions between Glu, GABA, and IGF-1 in vitro and in normal animals raises the question of whether and/or how the Glu/GABA system interacts with IGF-1 post-injury. This systematic review was undertaken to explore works addressing this question among adults with a history of traumatic brain injury (TBI) and/or cerebrovascular accident (CVA; stroke). The literature was searched for human and animal studies and only four animal papers met inclusion criteria. The SYRCLE criteria was used to evaluate risk of bias; results varied between categories and papers. All the included studies, one on TBI and three on stroke, supported the molecular relationship between the excitatory and IGF-1 systems; two studies provided direct, detailed molecular evidence. The results point to the importance of research on the role of this protective system in pathological brain injury; a hypothetical proposal for future studies is presented.
