Neonatal rat hypoxia-ischemia: long-term rescue of striatal neurons and motor skills by combined antioxidant-hypothermia treatment.

Full Abstract

Perinatal hypoxia-ischemia can cause long-term neurological and behavioral disability. Recent multicenter clinical trials suggest that moderate hypothermia, within 6 h of birth, offers significant yet incomplete protection. We investigated the effect of combined treatment with the antioxidant N-tert-butyl-(2-sulfophenyl)-nitrone (S-PBN) and moderate hypothermia on long-term neuronal injury and behavioral disability. S-PBN or its diluent was administered 12-hourly to rats from postnatal day (PN) 7 to 10. On PN8, hypoxia-ischemia was induced. Immediately post-hypoxia, additional S-PBN and 6 h of moderate hypothermia or additional diluent and 6 h of normothermia were administered. At 1 week, and at 11 weeks, after hypoxia-ischemia, the absolute number of surviving medium-spiny neurons was measured in the coded right striatum. In a separate experiment, skilled forepaw ability was investigated in coded 9- to 11-week-old rats. Normal, uninjured animals were also tested for motor skills at 9- to 11-weeks-of-age. The combination of S-PBN and moderate hypothermia provided statistically significant short- and long-term protection of the striatal medium-spiny neurons to normal control levels. This combinatorial treatment also preserved fine motor skills to normal control levels. The impressive histological and functional preservation suggests that S-PBN and moderate hypothermia is a safe and attractive combination therapy for perinatal hypoxia-ischemia.

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Author information

Author/s: Hobbs, Catherine E (CE); Oorschot, Dorothy E (DE);

Affiliation: Department of Anatomy and Structural Biology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Brain pathology (Zurich, Switzerland) (Brain Pathol), published in Switzerland. (Language: eng)

Reference: 2008-Jul; vol 18 (issue 3) : pp 443-54

Dates: Created 2008/06/05; Completed 2008/08/26;

PMID: 18371175, status: MEDLINE (last retrieval date: 11/6/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Animals, Newborn
Antioxidants - therapeutic use
Benzenesulfonates - therapeutic use
Combined Modality Therapy
Corpus Striatum - drug effects; pathology
Hypothermia, Induced

Hypothermia, Induced
Hypoxia-Ischemia, Brain - pathology; therapy
Male
Motor Skills - drug effects; physiology
Neurons - drug effects; pathology
Rats
Rats, Sprague-Dawley

Associated Chemicals: Antioxidants (0) ; Benzenesulfonates (0) ; N-tert-butyl-(2-sulfophenyl)nitrone (113443-50-8)

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