Effect of late treatment with gamma-hydroxybutyrate on the histological and behavioral consequences of transient brain ischemia in the rat.

Abstract

It has been previously described that gamma-hydroxybutyrate (GHB) provides significant protection against transient global cerebral ischemia in the rat (four vessel occlusion model), when given 30 min before or 10 min after artery occlusion. Here, we show that in the same rat model, significant protection can also be obtained when treatment is started 2 h after the ischemic episode. In saline-treated animals, 30 min of global ischemia followed by reperfusion caused a massive loss of neurons in the hippocampal CA1 subfield (examined 63 days after the ischemic episode), and an impairment of sensory-motor performance (tested on the 51st and 63rd days after ischemia) and of spatial learning and memory (evaluated starting 46 days after the ischemic episode). Treatment with GHB--300 mg/kg intraperitoneally (i.p.) 2 h after the ischemia-reperfusion episode, followed by 100 mg/kg i.p. twice daily for the following 10 days--afforded a highly significant protection, against both histological damage and sensory-motor and learning-memory impairments. These data further suggest the possible therapeutic effectiveness of GHB in brain ischemia, and indicate that the underlying mechanism of action involves non-immediate steps of the ischemia-induced cascade of events.

• Authors: Alessandra Ottani, Anna Valeria Vergoni, Sabrina Saltini, Chiara Mioni, Daniela Giuliani, Marta Bartiromo, Davide Zaffe, Annibale R Botticelli, Anna Ferrari, Alfio Bertolini, Susanna Genedani
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 485 Issue 1-3 Pg. 183-91 (Feb 06 2004) ISSN: 0014-2999 [Print] Netherlands
• PMID: 14757139 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Sodium Oxybate

Topics

• Animals
• Hippocampus (drug effects, pathology)
• Immunohistochemistry
• Ischemic Attack, Transient (pathology, prevention & control)
• Maze Learning (drug effects, physiology)
• Rats
• Rats, Wistar
• Sodium Oxybate (pharmacology, therapeutic use)
• Time Factors