In Vivo Brain GSH: MRS Methods and Clinical Applications

Abstract

Glutathione (GSH) is an important antioxidant implicated in several physiological functions, including the oxidation−reduction reaction balance and brain antioxidant defense against endogenous and exogenous toxic agents. Altered brain GSH levels may reflect inflammatory processes associated with several neurologic disorders. An accurate and reliable estimation of cerebral GSH concentrations could give a clear and thorough understanding of its metabolism within the brain, thus providing a valuable benchmark for clinical applications. In this context, we aimed to provide an overview of the different magnetic resonance spectroscopy (MRS) technologies introduced for in vivo human brain GSH quantification both in healthy control (HC) volunteers and in subjects affected by different neurological disorders (e.g., brain tumors, and psychiatric and degenerative disorders). Additionally, we aimed to provide an exhaustive list of normal GSH concentrations within different brain areas. The definition of standard reference values for different brain areas could lead to a better interpretation of the altered GSH levels recorded in subjects with neurological disorders, with insights into the possible role of GSH as a biomarker and therapeutic target.

α-Lipoic Acid Strengthens the Antioxidant Barrier and Reduces Oxidative, Nitrosative, and Glycative Damage, as well as Inhibits Inflammation and Apoptosis in the Hypothalamus but Not in the Cerebral Cortex of Insulin-Resistant Rats

“…GSH also maintains protein thiols in the reduced state and regulates gene expression (including inflammatory and insulin signaling pathways), as well as modulates neuronal differentiation and cell death. It is postulated that disturbances in glutathione metabolism may impair cerebral functioning in neurodegenerative diseases and diabetes [ 35 – 37 ]. Indeed, diminished glutathione concentration was observed in patients with AD, PD, ALS, and Huntington's disease [ 38 – 44 ].…”

Is There a Glutathione Centered Redox Dysregulation Subtype of Schizophrenia?

“…Among the MRS studies specifically optimized for GSH detection, 7T studies [65,183] report higher effect sizes GSH reduction in schizophrenia compared to 3T [55,184] Current methods for measuring human brain intracortical GSH levels via MRS in conjunction with other critically relevant metabolites of the cortical microcircuit such as glutamate and GABA currently have quantification precision in the range of 20-40%. The use of MRS methods optimized for one of these key metabolites improves the quantification precision below 10% for one metabolite at the detriment of others (see [185] for a detailed review). Some recent developments to study redox status in vivo utilizing hyperpolarized 13 C N-acetyl cysteine [186,187] or thiol-water proton exchange saturation transfer are promising to extend our insights into the glutathione system.…”

Cerebral Venous Thrombosis: A Challenging Diagnosis; A New Nonenhanced Computed Tomography Standardized Semi-Quantitative Method

“…When CVST is suspected, CT or MR venography are indicated. Contrast enhanced studies should only be performed if the suspicion of CVST is well founded, and the benefits outweigh the risks of further radiation exposure and administration of iodinated or gadolinium-based contrast, which may lead to brain deposition [ 15 , 16 ] and different types of toxicity [ 17 , 18 , 19 ].…”

“…Therefore, the availability of a quantitative spiral CT-scan diagnostic parameter, easy-to-obtain and with good sensitivity and specificity, could aid the diagnosis of CVST in an emergency setting. Several studies investigated the quantitative measurement of density of dural venous sinuses involved by thrombosis using non enhanced CT images with a retrospective approach [ 19 , 20 ]. This study aims to test a standardized ROI-based method to assess sinus thrombosis ignoring a priori the site of CVST.…”