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.
Sadasivan
Shankar
S
Division of Pediatric Emergency Medicine, Rainbow Babies & Children's Hospital/Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
Maher
Timothy J
TJ
Quang
Lawrence S
LS
D015107:4-Butyrolactone / Q000494:pharmacology*; D000818:Animals; D002072:Butylene Glycols / Q000494:pharmacology*; D002539:Cerebral Arterial Diseases / Q000139:chemically induced / Q000517:prevention & control*; D020244:Infarction, Middle Cerebral Artery / Q000139:chemically induced*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012978:Sodium Oxybate / Q000494:pharmacology*
D002072:Butylene Glycols; D012978:Sodium Oxybate; D015107:4-Butyrolactone