sodium-oxybate and Infarction--Middle-Cerebral-Artery

gamma-Hydroxybutyrate (GHB), a natural metabolite of gamma-aminobutyric acid and a drug used in humans to promote slow-wave sleep and treat narcolepsy, has been suggested to protect against ischemic stroke at high doses. This study aimed to assess recovery-promoting effects of GHB at a low dose similar to that used in patients.. Adult mice, subjected to 30 min of intraluminal middle cerebral artery occlusion, were intraperitoneally treated with GHB (100 mg/kg, twice/day, 8 h apart) or saline for 10 days. Motor recovery was evaluated by the grip strength test. The brain lesion was assessed by cresyl violet and NeuN staining 5 weeks after stroke. Expression of neuroplasticity-related genes (GAP43, c-jun, neurocan and ephrin B1) was analyzed by Taqman real-time PCR.. GHB-treated mice regained their body weight faster and recovered grip strength (3 weeks after stroke) more quickly than saline-treated mice. This was noteworthy as GHB did not influence ischemia-induced brain injury, as revealed by cresyl violet and neuronal staining. The Taqman PCR assay revealed a decreased expression of c-jun and neurocan in the ischemic striatum of GHB-treated mice in comparison to saline-treated mice.. GHB at a low dose accelerates neurological recovery following ischemic stroke. Further studies are necessary to determine the potential relationship between GHB, neuroplasticity, sleep and stroke recovery.

Topics: Adjuvants, Anesthesia; Animals; Brain Ischemia; Disease Models, Animal; Ephrin-B1; Gene Expression; Infarction, Middle Cerebral Artery; JNK Mitogen-Activated Protein Kinases; Male; Mice; Mice, Inbred C57BL; Nerve Tissue Proteins; Neurocan; Neuronal Plasticity; Proteoglycans; Recovery of Function; Sodium Oxybate

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.

Topics: 4-Butyrolactone; Animals; Butylene Glycols; Cerebral Arterial Diseases; Infarction, Middle Cerebral Artery; Male; Rats; Rats, Sprague-Dawley; Sodium Oxybate