Saturday, May 27, 2023

Molecular mechanisms of ischemia and glutamate excitotoxicity

Yes, we've known of excitoxicity and interventions for over a decade, why the fuck didn't you take all this old information and create a protocol for recovery from this?

Your doctors', researchers', and hospitals' reasons for doing nothing? There is absolutely no excuse for doing nothing.

Laziness? Incompetence? Or just don't care? No leadership? No strategy? Not my job? Not my Problem?

Molecular mechanisms of ischemia and glutamate excitotoxicity


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https://doi.org/10.1016/j.lfs.2023.121814Get rights and content
Under a Creative Commons license
open access

Highlights

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    Excitotoxicity is considered the main mechanism of cell death in ischemic stroke.

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    Protection against excitotoxicity goes beyond targeting the postsynaptic NMDAR.

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    The search for biomarkers to aid clinical management of stroke is a growing field.

Abstract

Excitotoxicity is classically defined as the neuronal damage caused by the excessive release of glutamate, and subsequent activation of excitatory plasma membrane receptors. In the mammalian brain, this phenomenon is mainly driven by excessive activation of glutamate receptors (GRs). Excitotoxicity is common to several chronic disorders of the Central Nervous System (CNS) and is considered the primary mechanism of neuronal loss of function and cell death in acute CNS diseases (e.g. ischemic stroke). Multiple mechanisms and pathways lead to excitotoxic cell damage including pro-death signaling cascade events downstream of glutamate receptors, calcium (Ca2+) overload, oxidative stress, mitochondrial impairment, excessive glutamate in the synaptic cleft as well as altered energy metabolism. Here, we review the current knowledge on the molecular mechanisms that underlie excitotoxicity, emphasizing the role of Nicotinamide Adenine Dinucleotide (NAD) metabolism. We also discuss novel and promising therapeutic strategies to treat excitotoxicity, highlighting recent clinical trials. Finally, we will shed light on the ongoing search for stroke biomarkers, an exciting and promising field of research, which may improve stroke diagnosis, prognosis and allow better treatment options.

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