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

The effect of gamma-hydroxybutyrate on the histological and behavioral cons equences of transient brain ischemia was studied in the four vessel occlusi on rat model. In saline-treated animals, 30 min ischemia caused a massive l oss 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 o r 10 min after arteries occlusion, followed by 100 mg/kg i.p. twice daily f or the following 10 days - afforded a highly significant protection (normal neurons on the 3rd, 10th, 15th and 65th day after ischemia: 88% and 91%, 8 0% and 80%, 91% and 90%, 72% and 71% in rats receiving the first dose befor e or after arteries occlusion, respectively). The ischemia-induced sensory- motor impairment was significantly attenuated in rats receiving the first d ose of gamma-hydroxybutyrate before arteries occlusion. Finally, the ischem ia-induced impairment in spatial learning and memory, evaluated starting 27 days after the ischemic episode, was significantly attenuated by gamma-hyd roxybutyrate, either injected first at 30 min before or 10 min after arteri es occlusion. Lower doses of gamma-hydroxybutyrate had no significant effec t. In conclusion, these results indicate that gamma-hydroxybutyrate provide s significant protection against both histological and behavioral consequen ces of transient global cerebral ischemia in rats. (C) 2000 Elsevier Scienc e B.V. All rights reserved.