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Partial neuroprotection by nNOS inhibition during profound asphyxia in preterm fetal sheep.
MedLine Citation:
PMID:  24120436     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Preterm brain injury is partly associated with hypoxia-ischemia starting before birth. Excessive nitric oxide production during HI may cause nitrosative stress, leading to cell membrane and mitochondrial damage. We therefore tested the hypothesis that therapy with a new, selective neuronal nitric oxide synthase (nNOS) inhibitor, JI-10 (0.022mg/kg bolus, n=8), given 30min before 25min of complete umbilical cord occlusion was protective in preterm fetal sheep at 101-104 d gestation (term is 147 d), compared to saline (n=8). JI-10 had no effect on fetal blood pressure, heart rate, carotid and femoral blood flow, total EEG power, nuchal activity, temperature or intracerebral oxygenation on near-infrared spectroscopy during or after occlusion. JI-10 was associated with later onset of post-asphyxial seizures compared with saline (p<0.05), and attenuation of the subsequent progressive loss of cytochrome oxidase (p<0.05). After 7days recovery, JI-10 was associated with improved neuronal survival in the caudate nucleus (p<0.05), but not the putamen or hippocampus, and more CNPase positive oligodendrocytes in the periventricular white matter (p<0.05). In conclusion, prophylactic nNOS inhibition before profound asphyxia was associated with delayed onset of seizures, slower decline of cytochrome oxidase and partial white and grey matter protection, consistent with protection of mitochondrial function.
Authors:
Paul P Drury; Joanne O Davidson; Lotte G van den Heuij; Sidhartha Tan; Richard B Silverman; Haitao Ji; Arlin B Blood; Mhoyra Fraser; Laura Bennet; Alistair Jan Gunn
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-10-9
Journal Detail:
Title:  Experimental neurology     Volume:  -     ISSN:  1090-2430     ISO Abbreviation:  Exp. Neurol.     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2013-10-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370712     Medline TA:  Exp Neurol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013.
Affiliation:
Department of Physiology, University of Auckland, Auckland, New Zealand. Electronic address: p.drury@auckland.ac.nz.
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