Neuroprotection and neurodegenerative disease.
This paper will focus on commonalities in the aetiology and pathology in five areas of neurological disease with illustrative examples of therapy. Possibilities of multimodal and neuroprotective therapies in human disease, employing currently available drugs and showing evidence of neuroprotective potential in animal models, are discussed. By definition, neuroprotection is an effect that may result in salvage, recovery or regeneration of the nervous system, its cells, structure and function. It is thought that there are many neurochemical modulators of nervous system damage. In epilepsy, excessive glutamate-mediated neurotransmission, impaired voltage sensitive sodium and calcium channel functioning, impaired GABA-mediated inhibition and alterations in acid base balance, when set in motion, may trigger a cascade of events leading to neuronal damage and cell death. Acute and chronic nervous system damage in response to an insult may lead to acute or delayed neuronal death, apoptotic cell death, neuronal degeneration, injury and loss, and gliosis. Cell death in the CNS following injury can occur in the manner of apoptosis, necrosis or hybrid forms. In general, NMDA receptor and non-NMDA receptor mediated excitotoxic injury results in neurodegeneration along an apoptosis-necrosis continuum. The effects of neuronal injury depend on factors including the degree of brain maturity or site of the lesion. There is some evidence supporting the hypothesis that neuroprotection may be a practical and achievable target using drugs already available, at present employed only for limited indications. Using these drugs early in the disease, may save decades of development of new drugs, which would require evaluation in animal studies, and human clinical trials. New drugs would also need to be shown to be safe and acceptable, physiologically not detrimental to humans and free from idiosyncratic adverse effects.
Vajda
Frank J E
FJ
Australian Centre for Clinical Neuropharmacology, St. Vincent's Hospital, Melbourne, Victoria, 3065, Australia. vajdafj@svhm.org.au
D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D004827:Epilepsy / Q000188:drug therapy; D006801:Humans; D016472:Motor Neuron Disease / Q000188:drug therapy; D009103:Multiple Sclerosis / Q000188:drug therapy; D019636:Neurodegenerative Diseases / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy
D018696:Neuroprotective Agents