Pictorial review of glutamate excitotoxicity: fundamental concepts for neuroimaging.

Neuroradiologists may encounter, on a daily basis, a challenging diversity of neurologic disorders, including stroke, trauma, epilepsy, and even neurodegenerative conditions, such as Huntington disease, AIDS dementia complex, and amyotrophic lateral sclerosis (1), but this spectrum of disease is not usually thought of as sharing the same mechanism of neuronal injury and death. These and a growing list of other neurologic disorders are now understood to share a final common destructive metabolic pathway called excitotoxicity (2, 3), which has been the focus of intense investigative efforts in the neurosciences over the past several decades (3–31). Excitotoxicity refers to an excessive activation of neuronal amino acid receptors. The specific type of excitotoxicity triggered by the amino acid glutamate is the key mechanism implicated in the mediation of neuronal death in many disorders. The discovery of excitotoxic injury is a major clue in the search for answers to such fundamental questions as why neurons die in disease states and what is the precise or critical mechanism of neuronal death. This overview introduces and reviews some of the major concepts of glutamate excitotoxicity. Familiarity with this intriguing pathologic process will enhance the understanding of the neuroimaging changes of many neuropathologic processes, facilitate a conceptual model for some of the newer treatment strategies for some disorders (ie, stroke and trauma), and perhaps cultivate new directions for neuroimaging. The organization of this article follows the excitotoxic process from the formation of glutamate to neuronal death. Glutamate excitotoxicity is a broad and rapidly evolving field of study with many important nuances that have necessarily been oversimplified or, unfortunately, omitted from this review for the sake of reasonable brevity. The reader is referred to the exponentially expanding literature and some of the