Short-term dose-response characteristics of 2-iminobiotin immediately postinsult in the neonatal piglet after hypoxia-ischemia.

Abstract

BACKGROUND AND PURPOSE:

To determine the optimal dose of 2-iminobiotin (2-IB) for the treatment of moderate to severe asphyxia in a neonatal piglet model of hypoxia-ischemia.

METHODS:

Newborn piglets were subjected to a 30-minute hypoxia-ischemia insult and randomly treated with vehicle or 2-IB (0.1 mg/kg, 0.2 mg/kg, or 1.0 mg/kg). aEEG background and seizure activity were scored after hypoxia-ischemia every 4 h until 24 h and at 48 h and neurobehavioral scores were obtained. Brain tissue was collected and processed for analysis of caspase-3 activity, histology, and tyrosine nitration.

RESULTS:

A dose range of 0.1 to 1.0 mg/kg/dose of 2-IB improved short-term outcome as demonstrated by an increased survival with a normal aEEG and decreased nitrotyrosine staining in the 2-IB-treated animals, indicating decreased cellular damage. Neurobehavior, caspase-3 activity in thalamus, and histology scores were not significantly different.

CONCLUSIONS:

Based on survival with a normal aEEG, 0.2 mg/kg 2-IB is likely to be the most appropriate dose for use in future clinical trials in neonates with perinatal hypoxia-ischemia.

• Authors: S Tracey Bjorkman, Zoe Ireland, Xiyong Fan, Willem M van der Wal, Kit C B Roes, Paul B Colditz, Cacha M P C D Peeters-Scholte
• Journal: Stroke (Stroke) Vol. 44 Issue 3 Pg. 809-11 (Mar 2013) ISSN: 1524-4628 [Electronic] United States
• PMID: 23362078 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biotin
• Nitric Oxide Synthase
• Caspase 3
• 2-iminobiotin

Topics

• Animals
• Asphyxia (drug therapy, etiology)
• Biotin (analogs & derivatives, therapeutic use)
• Brain (metabolism, pathology)
• Caspase 3 (metabolism)
• Dose-Response Relationship, Drug
• Electroencephalography
• Hypoxia-Ischemia, Brain (complications)
• Models, Animal
• Nitric Oxide Synthase (antagonists & inhibitors)
• Swine
• Time Factors
• Treatment Outcome