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

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

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The involvement of the excitatory amino acids glutamate and aspartate in cerebral ischemia and excitotoxicity is well-documented.Nevertheless,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely understudied.The release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the penumbra.Our findings indicated that the reversible loss of field excitatory 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 concentrations.These amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-D-aspartate receptors.Blocking N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during hypoxia.It 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 activation.Thus,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 injury.Understanding these pathways could highlight new therapeutic targets to mitigate brain injury.

cell swellingN-methyl-D-aspartate receptornon-excitatory amino acidsstrokesynaptic transmission

Victoria Jiménez Carretero、Iris Álvarez-Merz、Jorge Hernández-Campano、Sergei A.Kirov、Jesús M.Hernández-Guijo

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Department of Pharmacology and Therapeutic,School of Medicine,Univ.Autónoma de Madrid,Madrid,Spain

Ramón y Cajal Institute for Health Research(IRYCIS),Neurobiology-Research Service,Hospital Ramón y Cajal,Madrid,Spain

Institute of Neurobiology,Faculty of Mathematics and Natural Sciences,Heinrich Heine University Düsseldorf,Düsseldorf,Germany

Department of Neuroscience and Regenerative Medicine & Department of Neurosurgery,Medical College of Georgia at Augusta University,Augusta,GA,USA

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2025

10.4103/NRR.NRR-D-24-00536

中国神经再生研究(英文版)
中国康复医学会

中国神经再生研究(英文版)

影响因子：0.902
ISSN：1673-5374
年,卷(期)：2025.20(9)