Clinical validation of blood/brain glutamate grabbing in acute ischemic stroke

Annals of Neurology
Andrés da Silva-CandalFrancisco Campos

Abstract

Blood/brain-glutamate grabbing is an emerging concept in the treatment of acute ischemic stroke, where essentially the deleterious effects of glutamate after ischemia are ameliorated by coaxing glutamate to enter the bloodstream and thus reducing its concentration in the brain. Aiming to demonstrate the clinical efficacy of blood glutamate grabbers in patients with stroke, in this study, we resorted to a drug-repositioning strategy for the discovery of new glutamate-grabbing drugs. The glutamate-grabbing ability of 1,120 compounds (90% of which were drugs approved by the US Food and Drug Administration) was evaluated during an in vitro high-throughput screening campaign. Subsequently, the protective efficacy of the selected drugs was probed in an ischemic animal model and finally tested in stroke patients. Riboflavin (vitamin B2 ) was identified as the main hit compound. In ischemic animal models treated with riboflavin (1mg/kg), it was confirmed that blood glutamate reduction was associated with a significant reduction of infarct size. These results led to a randomized, double-blind, phase IIb clinical trial with patients with stroke. Fifty patients were randomized to 1 of the 2 study arms: the control group (placebo) and the ...Continue Reading

References

Dec 9, 1976·Nature·B B AndersonJ E Horn
Oct 1, 1996·Alcoholism, Clinical and Experimental Research·R F Anton
Jun 6, 2000·Journal of Biomolecular Screening·J H ZhangK R Oldenburg
Feb 15, 2007·European Journal of Clinical Nutrition·S Gariballa, R Ullegaddi
Oct 19, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shannon Reagan-ShawNihal Ahmad
Dec 10, 2008·Stroke; a Journal of Cerebral Circulation·Myron D Ginsberg
Jul 21, 2010·Experimental & Translational Stroke Medicine·Krystal L SchaarSean I Savitz
Jan 27, 2011·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Francisco CamposJosé Castillo
Jan 27, 2011·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Francisco CamposJosé Castillo
Nov 17, 2011·The International Journal of Biochemistry & Cell Biology·Francisco CamposJosé Castillo
Feb 3, 2012·Investigational New Drugs·Angela RubanVivian I Teichberg
Sep 4, 2013·The Journal of Clinical Investigation·María del Carmen GodinoJosé Sánchez-Prieto
Mar 14, 2014·Journal of Neural Transmission·Matthew BoykoAlexander Zlotnik
May 9, 2014·Cellular and Molecular Neurobiology·L KnappJ Toldi
Sep 24, 2014·Beilstein Journal of Organic Chemistry·Muhammad Ali SherazIqbal Ahmad
Oct 25, 2014·Antioxidants & Redox Signaling·Savita KhannaCameron Rink
Mar 5, 2015·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Andrés da Silva-CandalFrancisco Campos
Dec 15, 2015·Current Opinion in Pharmacology·Diana Amantea, Giacinto Bagetta
Dec 15, 2015·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·José CastilloFrancisco Campos
Jun 12, 2016·Biochimica Et Biophysica Acta·Anna StepanovaAlexander Galkin
Jan 18, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Cameron RinkSavita Khanna
Aug 5, 2017·Frontiers in Neurology·Eyad T Marashly, Saeed A Bohlega
Dec 21, 2017·Disease Models & Mechanisms·Héctor Fernández-SusavilaFrancisco Campos

❮ Previous
Next ❯

Citations

May 1, 2019·Antioxidants & Redox Signaling·Anna StepanovaAlexander Galkin
Jan 24, 2020·Current Opinion in Clinical Nutrition and Metabolic Care·Mette M Berger
Nov 26, 2019·Biochemistry. Biokhimii︠a︡·A Galkin
Apr 11, 2020·Oxidative Medicine and Cellular Longevity·Qiang ChuXiaodong Zheng
Oct 7, 2020·Annals of Clinical and Translational Neurology·Andrés da Silva-CandalRamón Iglesias-Rey
Sep 9, 2019·Molecular and Cellular Neurosciences·Vadim Ten, Alexander Galkin
Apr 23, 2021·Clinical Drug Investigation·Domenico PlantoneGiuseppe Rinaldi
Jun 25, 2021·Translational Stroke Research·Ramón Iglesias-ReyPablo Hervella

❮ Previous
Next ❯

Related Concepts

Related Feeds

Brain Ischemia

Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Acute Stroke

A stroke occurs when blood supply to the brain is interrupted depriving the brain of oxygen and nutrients. This feed focuses cerebrovascular accidents including ischemic and paralytic stroke.

Related Papers

Nihon rinsho. Japanese journal of clinical medicine
K Yasuda, M Hiraoka
Nihon rinsho. Japanese journal of clinical medicine
Kazuto Yasuda, Mami Hiraoka
Nihon rinsho. Japanese journal of clinical medicine
K Yasuda, Y Ishiwata
Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
José CastilloFrancisco Campos
© 2022 Meta ULC. All rights reserved