J Korean Child Neurol Soc.  1999 May;6(2):224-235.

Neuronal Rescue by Neurotrophic Factors in Human Fetal Cerebral Neuron Cultures Exposed to Oxygen Radical Injury

• Kim IS
• Woo YJ
• Ma JS
• Lee MC

Abstract

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.

MeSH Terms

Adenosine Triphosphate
Brain
Brain-Derived Neurotrophic Factor
Calcium
Central Nervous System
Ciliary Neurotrophic Factor
Cytoskeleton
Epidermal Growth Factor
Excitatory Amino Acids
Fibroblast Growth Factor 2
Gene Expression
Glucose
Glutamic Acid
Humans*
Membranes
Models, Theoretical
N-Methylaspartate
Nerve Growth Factor
Nerve Growth Factors*
Nervous System Diseases
Neurons*
Oxygen*
Peptide Hydrolases
Phosphotransferases
Reactive Oxygen Species
Receptors, Glutamate
Stroke
Adenosine Triphosphate
Brain-Derived Neurotrophic Factor
Calcium
Ciliary Neurotrophic Factor
Epidermal Growth Factor
Excitatory Amino Acids
Fibroblast Growth Factor 2
Glucose
Glutamic Acid
N-Methylaspartate
Nerve Growth Factor
Nerve Growth Factors
Oxygen
Peptide Hydrolases
Phosphotransferases
Reactive Oxygen Species
Receptors, Glutamate