Longitudinal alterations in gamma-aminobutyric acid (GABAA) receptor availability over ∼ 1 year following traumatic brain injury

Abstract

Longitudinal alterations of GABAA receptor availability following traumatic brain injury (TBI) have remained uncharacterized and may reflect changes in neuronal structure and function linked to cognitive recovery. We measured GABAA receptor availability using the tracer [11C]flumazenil in 9 adults with TBI (3-6 months after injury, subacute scan) and in 20 non-brain-injured individuals. A subset of subjects with TBI (n = 7) were scanned at a second chronic time-point, 7-13 months after their first scan and controls (n = 9) were scanned for a second time, 5-11 months after the first scan. After accounting for atrophy in subjects with TBI, we find broad decreases in GABAA receptor availability predominantly within the frontal lobes, striatum, and posterior-medial thalami; focal reductions were most pronounced in the right insula and anterior cingulate cortex (p < 0.05). Greater relative increase in GABAA receptor availability appeared globally between subacute and chronic scans. At >1 year post-injury, we find increased pallidal receptor availability compared to controls. Conversely, receptor availability remained depressed across the frontal cortices. Longitudinal improvement in executive attention correlated with increases in receptor availability across bilateral fronto-parietal cortical regions and the anterior-lateral aspects of the thalami. The specific observations of persistent bi-frontal lobe reductions and bilateral pallidal elevation are consistent with the anterior forebrain mesocircuit hypothesis for recovery of consciousness following a wide range of brain injuries; they provide novel correlative data in support of specific cellular mechanisms underlying persistent cognitive deficits. Collectively, these measurements support the use of [11C]flumazenil to track recovery of large-scale network function following brain injuries and measure response to therapeutics.

Preliminary Observations of Personalized Repetitive Magnetic Stimulation (PrTMS) Guided by EEG Spectra for Concussion

“…Several neurotransmitter types and pathways may play key roles in the deficits associated with concussion, and may represent potential therapeutic targets. For example, reduced levels of the neurotransmitter GABA over one year following traumatic brain injury were measured by Kang et al (2022) [ 64 ]. In the same study, longitudinal improvement in executive attention correlated with increased GABA receptor availability.…”

Brain Fluid Clearance After Traumatic Brain Injury Measured Using Dynamic Positron Emission Tomography

“…PET data were binned into 22 frames in a 400 × 400 matrix with a voxel size of 1.082 × 1.082 × 2.025 mm 3 . See Kang and colleagues 29 for details.…”

“…FMZ binds to gamma-aminobutyric acid type A receptors expressed by neurons throughout the brain and is considered to reflect neuronal integrity. 29 We focus not on the pattern of FMZ binding (the typical use of PET), but rather on the washout of FMZ from the ventricle (where there is no binding) as a measure of fluid clearance. We also compare ventricular clearance to (previously) MRI-measured ALPS index, 11 considered to specifically reflect glymphatic function.…”

A Molecular Toolbox of Positron Emission Tomography Tracers for General Anesthesia Mechanism Research

“…In the latest report, [ 11 C] 28 was successfully prepared by the fully automated iMiDEV microfluidic radio-synthesizer with RCP > 98% and A m = 1912 ± 552 GBq/μmol, which greatly facilitated its clinical research. PET imaging of GABA A receptors with [ 11 C] 28 has been used to demonstrate changes in neuronal density, assess the targeting of novel drugs, and study epilepsy − and cortical damage after stroke or trauma, − as well as examine patients with Alzheimer’s disease , or toxic leukoencephalopathies, and assist other researches (cerebellar ataxia, , malignant gliomas, and primary dystonia).…”