Effect of late treatment with gamma-hydroxybutyrate on the histological and behavioral consequences of transient brain ischemia in the rat.
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.
Ottani
Alessandra
A
Section of Pharmacology, Department of Biomedical Sciences, University of Modena and Reggio Emilia, Via G. Campi 287, Modena 41100, Italy. alessandroottani@yahoo.it
Vergoni
Anna Valeria
AV
Saltini
Sabrina
S
Mioni
Chiara
C
Giuliani
Daniela
D
Bartiromo
Marta
M
Zaffe
Davide
D
Botticelli
Annibale R
AR
Ferrari
Anna
A
Bertolini
Alfio
A
Genedani
Susanna
S
D000818:Animals; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000517:prevention & control*; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012978:Sodium Oxybate / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors
D012978:Sodium Oxybate