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

The effect of g-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.. g-Hydroxybutyrate — 300 mgrkg intraperitoneallyi.p..30 min before or 10 min after arteries occlusion, followed by 100 mgrkg 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 g-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 g-hydroxybutyrate, either injected first at 30 min before or 10 min after arteries occlusion. Lower doses of g-hydroxybutyrate had no significant effect. In conclusion, these results indicate that g-hydroxybutyrate provides significant protection against both histological and behavioral consequences of transient global cerebral ischemia in rats

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

It has been previously described that g-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 ischemiainduced cascade of events