dynorphins and Central-Nervous-System-Diseases

Epilepsy is a significant health problem. Despite the widespread use of both classic and newer pharmacological agents that target ion channels, amino acid transmission or receptors, there are numerous examples of mono- or polytherapy being ineffective. Seizures that are secondary to CNS infections are among the most refractory medically, and thus insult-specific agents are desirable. Recently, the study of the neuropharmacological actions of dynorphin in CNS viral injury has yielded new insights into epileptogenesis and epilepsy treatment. The opioid neuropeptide dynorphin modulates neuronal excitability in vitro in hippocampal slices and potentiates endogenous anti-ictal (i.e. protective) processes in animal models and humans. This work has renewed interest in the role of dysregulation of dynorphin in the pathogenesis of refractory seizures, including encephalitic seizures. The important role of dynorphin in epilepsy is also supported by new models of symptomatic epilepsies based on viral-induced seizures.

Topics: Animals; Central Nervous System Diseases; Disease Models, Animal; Dynorphins; Epilepsy; Hippocampus; Humans; Rats; Seizures

It has been proposed that endogenous opioids play a pathophysiologic role in the secondary injury that follows spinal trauma, brain trauma, and cerebral ischemia. Opiate antagonists, at high doses, have been found to improve outcome in various experimental models of central nervous system injury. Thyrotropin-releasing hormone, which appears to act in part as a functional antagonist of opioid systems, has proved effective in the treatment of experimental spinal cord and brain trauma. The literature relating to these developments is reviewed, with emphasis on the potential clinical application of these classes of substances.

Topics: Animals; Cats; Central Nervous System Diseases; Dynorphins; Humans; Ischemic Attack, Transient; Naloxone; Narcotic Antagonists; Narcotics; Rabbits; Spinal Cord Injuries; Thyrotropin-Releasing Hormone