Neuroprotective effect of gamma-hydroxybutyrate in transient global cerebral ischemia in the rat.

The effect of gamma-hydroxybutyrate on the histological and behavioral consequences of transient brain ischemia was studied in the four vessel occlusion rat model. In saline-treated animals, 30 min ischemia caused a massive loss of neurons in the hippocampal CA1 subfield (normal neurons: 14%, 5%, 23% and 30% on the 3rd, 10th, 15th and 65th day after ischemia, respectively). gamma-Hydroxybutyrate - 300 mg/kg intraperitoneally (i.p.) 30 min before or 10 min after arteries occlusion, followed by 100 mg/kg i.p. twice daily for the following 10 days - afforded a highly significant protection (normal neurons on the 3rd, 10th, 15th and 65th day after ischemia: 88% and 91%, 80% and 80%, 91% and 90%, 72% and 71% in rats receiving the first dose before or after arteries occlusion, respectively). The ischemia-induced sensory-motor impairment was significantly attenuated in rats receiving the first dose of gamma-hydroxybutyrate before arteries occlusion. Finally, the ischemia-induced impairment in spatial learning and memory, evaluated starting 27 days after the ischemic episode, was significantly attenuated by gamma-hydroxybutyrate, either injected first at 30 min before or 10 min after arteries occlusion. Lower doses of gamma-hydroxybutyrate had no significant effect. In conclusion, these results indicate that gamma-hydroxybutyrate provides significant protection against both histological and behavioral consequences of transient global cerebral ischemia in rats.
AuthorsA V Vergoni, A Ottani, A R Botticelli, D Zaffe, L Guano, A Loche, S Genedani, G L Gessa, A Bertolini
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 397 Issue 1 Pg. 75-84 (May 26 2000) ISSN: 0014-2999 [Print] NETHERLANDS
PMID10844101 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Neuroprotective Agents
  • Sodium Oxybate
  • Animals
  • Brain Ischemia (physiopathology)
  • Hippocampus (drug effects, pathology)
  • Learning (drug effects)
  • Male
  • Memory (drug effects)
  • Neurons (drug effects, pathology)
  • Neuroprotective Agents (pharmacology)
  • Psychomotor Performance (drug effects)
  • Rats
  • Rats, Wistar
  • Sodium Oxybate (pharmacology)
  • Somatosensory Cortex (drug effects, physiopathology)
  • Spatial Behavior (drug effects)

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