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.
Vergoni
A V
AV
Section of Pharmacology, Department of Biomedical Sciences, University of Modena and Reggio Emilia, Via G. Campi 287, 41100, Modena, Italy.
Ottani
A
A
Botticelli
A R
AR
Zaffe
D
D
Guano
L
L
Loche
A
A
Genedani
S
S
Gessa
G L
GL
Bertolini
A
A
D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007858:Learning / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012978:Sodium Oxybate / Q000494:pharmacology*; D013003:Somatosensory Cortex / Q000187:drug effects / Q000503:physiopathology; D013037:Spatial Behavior / Q000187:drug effects
D018696:Neuroprotective Agents; D012978:Sodium Oxybate