Protective Role of Glutathione in the Hippocampus after Brain Ischemia
Open Access
- 21 July 2021
- journal article
- review article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 22 (15), 7765
- https://doi.org/10.3390/ijms22157765
Abstract
Stroke is a major cause of death worldwide, leading to serious disability. Post-ischemic injury, especially in the cerebral ischemia-prone hippocampus, is a serious problem, as it contributes to vascular dementia. Many studies have shown that in the hippocampus, ischemia/reperfusion induces neuronal death through oxidative stress and neuronal zinc (Zn2+) dyshomeostasis. Glutathione (GSH) plays an important role in protecting neurons against oxidative stress as a major intracellular antioxidant. In addition, the thiol group of GSH can function as a principal Zn2+ chelator for the maintenance of Zn2+ homeostasis in neurons. These lines of evidence suggest that neuronal GSH levels could be a key factor in post-stroke neuronal survival. In neurons, excitatory amino acid carrier 1 (EAAC1) is involved in the influx of cysteine, and intracellular cysteine is the rate-limiting substrate for the synthesis of GSH. Recently, several studies have indicated that cysteine uptake through EAAC1 suppresses ischemia-induced neuronal death via the promotion of hippocampal GSH synthesis in ischemic animal models. In this article, we aimed to review and describe the role of GSH in hippocampal neuroprotection after ischemia/reperfusion, focusing on EAAC1.Funding Information
- Japan Society for the Promotion of Science (19K09510, 19J23044)
This publication has 82 references indexed in Scilit:
- Oral administration of glutathione improves memory deficits following transient brain ischemia by reducing brain oxidative stressNeuroscience, 2013
- EAAC1 Gene Deletion Alters Zinc Homeostasis and Exacerbates Neuronal Injury after Transient Cerebral IschemiaJournal of Neuroscience, 2010
- Clioquinol Inhibits Zinc-Triggered Caspase Activation in the Hippocampal CA1 Region of a Global Ischemic Gerbil ModelPLOS ONE, 2010
- Time-of-day determines neuronal damage and mortality after cardiac arrestNeurobiology of Disease, 2009
- Structural Features of Ischemic Damage in the HippocampusThe Anatomical Record, 2009
- Detergent‐Insoluble EAAC1/EAAT3 Aberrantly Accumulates in Hippocampal Neurons of Alzheimer's Disease PatientsBrain Pathology, 2009
- Circadian Variation in the Timing of Stroke OnsetStroke, 1998
- Memory Formation: The Sequence of Biochemical Events in the Hippocampus and Its Connection to Activity in Other Brain StructuresNeurobiology of Learning and Memory, 1997
- Circadian variation in the frequency of ischemic stroke.Stroke, 1990
- Diurnal variation in occurrence of strokes.Stroke, 1977