Effect of γ-hydroxybutyrate in two rat models of focal cerebral damage

• Published in: Brain research 2003-10, Vol.986 (1), p.181-190
• Main Authors: Ottani, Alessandra, Saltini, Sabrina, Bartiromo, Marta, Zaffe, Davide, Renzo Botticelli, Annibale, Ferrari, Anna, Bertolini, Alfio, Genedani, Susanna
• Format: Article
• Language: English
• Subjects: Animals; Apomorphine - antagonists & inhibitors; Biological and medical sciences; Brain - drug effects; Brain - pathology; Brain - physiopathology; Brain Ischemia - drug therapy; Brain Ischemia - pathology; Brain Ischemia - physiopathology; Cerebral excitotoxicity; Cerebral ischemia; Circling behavior; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelin-1; Endothelin-1 - antagonists & inhibitors; Immunohistochemistry; Kainic acid; Kainic Acid - antagonists & inhibitors; Learning - drug effects; Male; Medical sciences; Memory Disorders - drug therapy; Motor Activity - drug effects; Nerve Degeneration - drug therapy; Nerve Degeneration - physiopathology; Nerve Degeneration - prevention & control; Neurology; Neuroprotective Agents - pharmacology; Neurotoxins - antagonists & inhibitors; Rats; Rats, Wistar; Sensory-motor test; Sodium Oxybate - pharmacology; Spatial learning; Vascular diseases and vascular malformations of the nervous system; γ-Hydroxybutyrate
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(03)03252-9

γ-Hydroxybutyrate (GHB) and its lactone, γ-butyrolactone (GBL) have been previously shown to produce a protective effect in animal models of cerebral ischaemia/hypoxia, as well as in human conditions of head injury-induced coma. The aim of the present research was to study the effect of GHB in experimental conditions of focal cerebral damage, either induced by ischaemia or excitotoxicity. Under general anaesthesia, rats were injected into the right striatum with either endothelin-1 (ET-1, 0.43 nmol) or kainic acid (7.5 nmol) in a volume of 1 μl. Sham-lesioned rats received 1 μl of the solvent. Both ET-1- and kainic acid-lesioned rats were randomly assigned to one of the following intraperitoneal (i.p.) treatments: (i) and (ii) GHB, 100 or 300 mg kg −1 2 h after the lesion, followed by 50 or 100 mg kg −1, respectively, every 12 h; (iii) saline, 2 ml kg −1, same schedule. Sham animals were treated with saline, 2 ml kg −1, same schedule. Treatments lasted for 10 days. The higher dose of GHB produced a significant protection against the ET-1-induced impairments in sensory-motor orientation and coordinated limb use (evaluated 24 and 42 days after the lesion) and in place learning and memory (Morris test, performed 19 and 39 days after the lesion). The same dose regimen reduced the circling behaviour induced by apomorphine in kainate-lesioned rats (10 days after the lesion), and limited or prevented at all the histological damage produced either by ET-1 or by kainic acid (evaluated 43 or 10 days after the lesion, respectively). These results show that GHB limits both histological and functional consequences of a focal ischaemic or excitotoxic insult of the brain, in rats, even if the treatment is started 2 h after the lesion.