| Neuronal Rescue by Neurotrophic Factors in Human Fetal Cerebral Neuron Cultures Exposed to Oxygen Radical Injury. |
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In Suk Kim, Young Jong Woo, Jae Sook Ma, Min Cheol Lee |
1Department of Pediatrics, Chonnam National University Medical School, Kwangju, Korea.
2Department of Pathology, Chonnam National University Medical School, Kwangju, Korea.
3Chonnam National University Medical School, Research Institute of Medical Sciences, Kwangju, Korea. |
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| Abstract |
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As for the pathomechanism for cerebral damage in stroke, following steps have been proposed the reduction of oxygen and glucose levels in the affected brain results in a decreased ATP levels, and then excessive release and reduced uptake of the excitatory amino acid (EAA) glutamate; activation of both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors by EAA forced massive calcium influx into neurons; the excess intracellular calcium causes structural damage to cytoskeleton and membranes as a result of activation of kinases, proteases, and reactive oxygen species (ROS). Both ROS and excitotoxicity are pathogenetic events related to stroke as well as a wide range of other neurological disorders. It has become clear that neurotrophic factors in the central nervous system (CNS) play major roles in the development and maintenance of neural circuits, and that ischemic and other insults to the brain induce marked changes of gene expression for neurotrophic factors and their receptors, and the functional affects of the changes are related to protection against neuronal damage and stimulation of sprouting and synaptic reorganization. These neurotrophic factors include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3, 45 (NT-3, 4/5, basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF), epidermal growth factor (EGF), ciliary neurotrophic factor (CNTF) and midkine (MK). In the present study, a hypothesis is made that the neuronal damage found in the stroke patients may be due to the metabolic derangement partly caused by oxygen radicals. To test this hypothesis, the experimental model was developed using tissue culture system and the protective effect of several neurotrophic factors against ROS-mediated cell injury was evaluated. |
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