Journal
NEUROBIOLOGY OF DISEASE
Volume 20, Issue 3, Pages 871-880Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2005.05.024
Keywords
inducible nitric oxide synthase; neuroprotection; perinatal stroke; preconditioning; newborn; prenatal hypoxia
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Funding
- NIGMS NIH HHS [R01 GM065211] Funding Source: Medline
- NINDS NIH HHS [R01 NS045983] Funding Source: Medline
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The incidence of perinatal stroke is similar to 0.025%. About two thirds of these patients develop long-lasting neurological deficits. Preconditioning-induced neuroprotection, a phenomenon in which application of a stimulus induces brain ischemic tolerance, is investigated to improve outcome after a perinatal stroke. We applied prenatal hypoxia to fetuses by exposing 22-day pregnant mother rats to 15% oxygen for 30 min and subjected newborns with or without this prenatal hypoxia to brain ischemia 48 It later. Newborns with the prenatal hypoxia had a lower mortality rate, less brain tissue and neuronal loss and fewer active caspase 3 (an indicator for cell apoptosis) positive brain cells than newborns with the brain ischemia only This neuroprotection was abolished by an inhibitor of inducible nitric oxide synthase (iNOS). The expression of iNOS proteins but not endothelial and neuronal NOS proteins was increased by the prenatal hypoxia. Thus, the prenatal hypoxia-induced neuroprotection may be iNOS-dependent. (c) 2005 Elsevier Inc. All rights reserved.
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