Excitotoxicitate

Excitotoxicitate (excitotoxicity) is a pathological process in which neurons are damaged or killed due to excessive activation of glutamate receptors, particularly NMDA and AMPA receptors, leading to intracellular calcium overload.

Under pathological conditions, excessive glutamate release or impaired clearance by astrocytes increases extracellular glutamate. NMDA/AMPA receptor overactivation causes Ca2+ influx, activating calcium-dependent enzymatic pathways (proteases, phospholipases, endonucleases), mitochondrial dysfunction, reactive oxygen species, lipid peroxidation, and ultimately cell death by necrosis or apoptosis.

It is commonly observed in ischemic stroke, traumatic brain injury, and spinal cord injury, and is implicated in chronic neurodegenerative diseases such as ALS, Alzheimer's disease, and Huntington's disease, as well as in seizures.

Therapeutic strategies aim to limit excitotoxicity by modulating glutamate signaling, enhancing astrocytic uptake, blocking NMDA receptors, or scavenging reactive species. Clinical success has been limited by side effects and the complexity of glutamate signaling, but the concept remains central to acute CNS injury and neurodegenerative research.