Rapid NMDA receptor phosphorylation and oxidative stress precede striatal neurodegeneration after hypoxic ischemia in newborn piglets and are attenuated with hypothermia
| Autor: | Lee J. Martin, Dawn Mueller-Burke, Raymond C. Koehler |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Time Factors Swine Hypothermia Nitric Oxide Synthase Type I Biology Protein oxidation medicine.disease_cause Neuroprotection Receptors N-Methyl-D-Aspartate Article Nitric oxide chemistry.chemical_compound Developmental Neuroscience Internal medicine medicine Serine Animals Phosphorylation Free-radical theory of aging Neurons Analysis of Variance Neurodegeneration Neurodegenerative Diseases medicine.disease Corpus Striatum Disease Models Animal Oxidative Stress Endocrinology Biochemistry chemistry nervous system Animals Newborn Hypoxia-Ischemia Brain Lipid Peroxidation medicine.symptom Oxidative stress Developmental Biology |
| Zdroj: | International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience. 26(1) |
| ISSN: | 0736-5748 |
| Popis: | The basal ganglia of newborns are extremely vulnerable to hypoxic ischemia (HI). Striatal neurons undergo prominent necrosis after HI. The mechanisms for this degeneration are not well understood. Post-asphyxic hypothermia ameliorates the striatal necrosis, but the mechanisms of hypothermia-induced neuroprotection are not known. We used a newborn piglet model of hypoxic-asphyxic cardiac arrest to test the hypotheses that N-methyl-D-aspartate receptor activation and free radical damage coexist, prior to neurodegeneration, early after resuscitation, and that these changes are attenuated with hypothermia. Piglets were subjected to 30 minutes of hypoxia followed by 7 minutes of airway occlusion, causing asphyxia cardiac arrest, and then were resuscitated and survived normothermically for 5 minutes, 3 hours, or 6 hours, or hypothermically for 3 hours. By 6 hours of normothermic recovery, 50% of neurons in putamen showed ischemic cytopathology. Striatal tissue was fractionated into membrane or soluble proteins and was assayed by immunoblotting for carbonyl modification, phosphorylation of the N-methyl-D-aspartate receptor subunit NR1, and neuronal nitric oxide synthase. Significant accumulation of soluble protein carbonyls was present at 3 hours (196% of control) and 6 hours (142% of control). Phosphorylation of serine-897 of NR1 was increased significantly at 5 minutes (161% of control) and 3 hours (226% of control) after HI. Phosphorylation of serine-890 of NR1 was also increased after HI. Membrane associated neuronal nitric oxide synthase was increased by 35% at 5 minutes. Hypothermia attenuated the oxidative damage and the NR1 phosphorylation in striatum. We conclude that neuronal death signaling in newborn striatum after HI is engaged rapidly through N-methyl-D-aspartate receptor activation, neuronal nitric oxide synthase recruitment, and oxidative stress. Postasphyxic, mild whole body hypothermia provides neuroprotection by suppressing N-methyl-D-aspartate receptor phosphorylation and protein oxidation. |
| Databáze: | OpenAIRE |
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