Targeting harmful effects of non-excitatory amino acids as an alternative therapeutic strategy to reduce ischemic damage

作     者：Victoria Jiménez Carretero Iris álvarez-Merz Jorge Hernández-Campano Sergei A.Kirov Jesús M.Hernández-Guijo 

作者机构：Department of Pharmacology and TherapeuticSchool of MedicineUniv.Autonoma de Madrid Ramón y Cajal Institute for Health Research (IRYCIS)Neurobiology-Research ServiceHospital Ramón y Cajal Institute of Neuro biologyFaculty of Mathematics and Natural Sciences Heinrich Heine University Dusseldorf Department of Neuroscience and Regenerative Medicine & Department of NeurosurgeryMedical College of Georgia at Augusta University 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究(英文))

年 卷 期：2025年第09期

页      面：2454-2463页

核心收录：

学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学] 

基　　金：supported by MICIU (grant number PID2021-128133NB-100/AEI/FEDER1 0.13039/501100011033 to JMHG) by the National Institutes of Health (grant number R01 NS083858 to SAK) the Intramural Grants Program IGPP00057 (to SAK) VIC enjoys a FPU contract from the Comunidad de Madrid (PIPF-2022/SAL-GL-25948) 

摘      要：The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is ***,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely *** release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the *** findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(L-alanine,glycine,L-glutamine,and L-serine) at their plasma *** amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-D-aspartate *** N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during *** is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-D-aspartate receptor ***,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain *** these pathways co uld highlight new therapeutic targets to mitigate brain injury.