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Gamma-hydroxybutyrate accelerates functional recovery after focal cerebral ischemia.

AbstractBACKGROUND AND PURPOSE:
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.
METHODS:
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.
RESULTS:
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.
CONCLUSION:
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.
AuthorsBo Gao, Ertugrul Kilic, Christian R Baumann, Dirk M Hermann, Claudio L Bassetti
JournalCerebrovascular diseases (Basel, Switzerland) (Cerebrovasc Dis) Vol. 26 Issue 4 Pg. 413-9 ( 2008) ISSN: 1421-9786 [Electronic] Switzerland
PMID18753748 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2008 S. Karger AG, Basel.
Chemical References
  • Adjuvants, Anesthesia
  • Efnb1 protein, mouse
  • Ephrin-B1
  • Ncan protein, mouse
  • Nerve Tissue Proteins
  • Neurocan
  • Proteoglycans
  • Sodium Oxybate
  • JNK Mitogen-Activated Protein Kinases
Topics
  • Adjuvants, Anesthesia (pharmacology)
  • Animals
  • Brain Ischemia (drug therapy)
  • Disease Models, Animal
  • Ephrin-B1 (genetics)
  • Gene Expression (drug effects)
  • Infarction, Middle Cerebral Artery (drug therapy)
  • JNK Mitogen-Activated Protein Kinases (genetics)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins (genetics)
  • Neurocan
  • Neuronal Plasticity (drug effects, physiology)
  • Proteoglycans (genetics)
  • Recovery of Function (drug effects, physiology)
  • Sodium Oxybate (pharmacology)

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