Excitotoxicity Mitigation refers to the clinical and biological strategies employed to reduce or prevent excitotoxicity, a pathological process where excessive or prolonged activation of excitatory amino acid receptors, particularly NMDA receptors by glutamate, leads to neuronal damage and death. Effective mitigation is a crucial neuroprotective goal in acute neurological events and chronic neurodegenerative conditions. This delicate balance is vital for maintaining neural network integrity and preventing cellular burnout.
Origin
The concept stems from early neuroscientific research identifying glutamate as the brain’s primary excitatory neurotransmitter and recognizing that its overstimulation is profoundly toxic to neurons. The term ‘mitigation’ emphasizes a clinical and therapeutic approach to dampen this harmful overactivity. Its relevance in hormonal health is noted as certain hormones can modulate the sensitivity of these excitatory receptors.
Mechanism
Mitigation strategies primarily involve modulating the activity of glutamate receptors, often through pharmacological agents that act as receptor antagonists or through endogenous neurosteroids like allopregnanolone that enhance inhibitory GABA signaling. This intervention helps restore the delicate electrochemical balance within the neuron, preventing the catastrophic influx of calcium ions that triggers cell death cascades, including mitochondrial dysfunction and oxidative stress. Maintaining proper neuronal homeostasis is the central objective.
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