Gamma-Hydroxybutyrate (GHB), gamma-butyrolactone (GBL), and 1,4-butanediol (1,4-BD) reduce the volume of cerebral infarction in rodent transient middle cerebral artery occlusion.

gamma-Hydroxybutyric acid (GHB), an endogenous organic acid catabolite of gamma-aminobutyric acid (GABA), has been shown to have tissue-protective effects in various organs, including the brain. We examined the potential neuroprotective effect of GHB and its chemical precursors, gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD), in the rodent ischemic stroke model by intraluminal filament middle cerebral artery occlusion (MCAO). Adult male Sprague-Dawley rats underwent transient left-sided MCAO and received intraperitoneal treatment with 300 mg/kg of GHB, GBL, 1,4-BD, or control vehicle given at 30 min before, as well as 180 and 360 min after the onset of ischemia. Infarct volumes were determined 24 h after MCAO. In transient MCAO, the mean volume of infarction for control rats was 464.4 +/- 17.9 cu.mm versus 273.6 +/- 53.1, 233.3 +/- 44.7, and 275.4 +/- 39.9 cu.mm for rats treated with 1,4-BD (P < 0.05), GBL (P < 0.05), and GHB (P < 0.05), respectively. We conclude that GHB, GBL, and 1,4-BD protect against rat focal cerebral ischemia from transient MCAO.