Pathways That Determine Neuronal Injury

Despite the immediate event, such as cardiac arrest or cerebral trauma, that may ultimately result in organic brain disease, specific cellular signal transduction pathways in the central nervous system ultimately influence the extent of neuronal injury. However, one must remember that it is multiple mechanisms, rather than a single cellular pathway, that determine neuronal survival during organic brain disease. Although neuronal injury associated with several disease entities, such as stroke, Alzheimer's disease, and Parkinson's disease, was initially believed to be irreversible, it has become increasingly evident that either acute or chronic modulation of the cellular and molecular environment within the brain can prevent or even reverse neuronal injury. Pharmacological manipulation of glutamate receptor activity and imidazole receptor binding agents have been shown to reduce the extent of ischemia within the penumbral zone. In addition, muscarinic agonists have been demonstrated to possibly influence neuronal plasticity. In order to develop rational, efficacious, and safe therapy against organic brain disease, it is vital to elucidate the cellular and molecular mechanisms that modulate neuronal injury. Some of these pathways include nitric oxide, programmed cell death, peptide growth factors, and metabotropic glutamate receptors.

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