Excitotoxicity

<p>In excitotoxicity, <a href="/facts/Neuron/G7CyTVdH">nerve cells</a> suffer damage or death when the levels of otherwise necessary and safe <a href="/facts/Neurotransmitter/LlpYFSU3">neurotransmitters</a> such as <a href="/facts/Glutamic_acid/7oXbNcvu">glutamate</a> become pathologically high, resulting in excessive stimulation of <a href="/facts/Cell_surface_receptor/0YGSjDdL">receptors</a>. For example, when <a href="/facts/Glutamate_receptor/MGwpHHUA">glutamate receptors</a> such as <a href="/facts/NMDA_receptor/BqMhXEbU">NMDA receptors</a> or <a href="/facts/AMPA_receptor/FJHDlvkg">AMPA receptors</a> encounter excessive levels of the excitatory neurotransmitter, glutamate, significant neuronal damage might ensue. Different mechanisms might lead to increased extracellular glutamate concentrations, e.g. reduced uptake by glutamate transporters (EAATs), synaptic hyperactivity, or abnormal release from different neural cell types. Excess glutamate allows high levels of <a href="/facts/Calcium_in_biology/wgUxKej5">calcium</a> ions (Ca2+) to enter the <a href="/facts/Cell_(biology)/bLM9UQvy">cell</a>. Ca2+ influx into cells activates a number of enzymes, including <a href="/facts/Phospholipase/kWbLYcA5">phospholipases</a>, <a href="/facts/Endonuclease/t9Y0d883">endonucleases</a>, and <a href="/facts/Proteases/G1ASdVat">proteases</a> such as <a href="/facts/Calpain/vebGUShd">calpain</a>. These enzymes go on to damage cell structures such as components of the <a href="/facts/Cytoskeleton/1sWlJRX9">cytoskeleton</a>, <a href="/facts/Cell_membrane/vAXSD0DT">membrane</a>, and DNA. In evolved, <a href="/facts/Complex_adaptive_system/mbhhM88D">complex adaptive systems</a> such as biological life it must be understood that mechanisms are rarely, if ever, simplistically direct. For example, NMDA, in subtoxic amounts, can block glutamate toxicity and induce neuronal survival. In addition to abnormally high neurotransmitter concentrations, also elevation of the extracellular potassium concentration, acidification and other mechanisms may contribute to excitotoxicity.  
</p><p>Excitotoxicity may be involved in <a href="/facts/Cancers/PVW6n1D0">cancers</a>, <a href="/facts/Spinal_cord_injury/D0vo3ArR">spinal cord injury</a>, <a href="/facts/Stroke/DwpjdzY0">stroke</a>, <a href="/facts/Traumatic_brain_injury/DTq110vw">traumatic brain injury</a>, <a href="/facts/Hearing_loss/7C78RpMP">hearing loss</a> (through <a href="/facts/Noise-induced_hearing_loss/3fvhFuDv">noise overexposure</a> or <a href="/facts/Ototoxicity/yXsCQ00n">ototoxicity</a>), and in <a href="/facts/Neurodegenerative_disease/HTDrVEqc">neurodegenerative diseases</a> of the <a href="/facts/Central_nervous_system/k8I6To97">central nervous system</a> such as <a href="/facts/Multiple_sclerosis/vghXl0IQ">multiple sclerosis</a>, <a href="/facts/Alzheimer%2527s_disease/w7Ad6tdg">Alzheimer's disease</a>, <a href="/facts/Amyotrophic_lateral_sclerosis/9fIXnNL4">amyotrophic lateral sclerosis</a> (ALS), <a href="/facts/Parkinson%2527s_disease/xpekKj6x">Parkinson's disease</a>, <a href="/facts/Alcoholism/KGPzpChp">alcoholism</a>, <a href="/facts/Alcohol_withdrawal_syndrome/FRX036Vk">alcohol withdrawal</a> or <a href="/facts/Hyperammonemia/11V7URmx">hyperammonemia</a> and especially over-rapid <a href="/facts/Benzodiazepine_withdrawal_syndrome/5ClvqCLB">benzodiazepine withdrawal</a>, and also <a href="/facts/Huntington%2527s_disease/2P6yCoeK">Huntington's disease</a>. Other common conditions that cause excessive glutamate concentrations around neurons are <a href="/facts/Hypoglycemia/BlAmuP6k">hypoglycemia</a>. Blood sugars are the primary energy source for glutamate removal from inter-synaptic spaces at the NMDA and AMPA receptor site. Persons in excitotoxic shock must never fall into hypoglycemia. Patients should be given 5% glucose (dextrose) IV drip during excitotoxic shock to avoid a dangerous build up of glutamate around NMDA and AMPA neurons. When 5% glucose (dextrose) IV drip is not available high levels of fructose are given orally. Treatment is administered during the acute stages of excitotoxic shock along with glutamate <a href="/facts/Receptor_antagonist/PuXHVNdV">antagonists</a>. Dehydration should be avoided as this also contributes to the concentrations of glutamate in the inter-synaptic cleft and "status epilepticus can also be triggered by a build up of glutamate around inter-synaptic neurons."
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Excitotoxicity open-in-new

Excitotoxicity