title: Decreased GABAB receptor function in the cerebellum and brain stem of hypoxic neonatal rats: role of glucose, oxygen and epinephrine resuscitation.
abstract: BACKGROUND
  Hypoxia during the first week of life can induce neuronal death in vulnerable brain regions usually associated with an impairment of cognitive function that can be detected later in life. The neurobiological changes mediated through neurotransmitters and other signaling molecules associated with neonatal hypoxia are an important aspect in establishing a proper neonatal care.
  
  
  METHODS
  The present study evaluated total GABA, GABAB receptor alterations, gene expression changes in GABAB receptor and glutamate decarboxylase in the cerebellum and brain stem of hypoxic neonatal rats and the resuscitation groups with glucose, oxygen and epinephrine. Radiolabelled GABA and baclofen were used for receptor studies of GABA and GABAB receptors respectively and Real Time PCR analysis using specific probes for GABAB receptor and GAD mRNA was done for gene expression studies.
  
  
  RESULTS
  The adaptive response of the body to hypoxic stress resulted in a reduction in total GABA and GABAB receptors along with decreased GABAB receptor and GAD gene expression in the cerebellum and brain stem. Hypoxic rats supplemented with glucose alone and with oxygen showed a reversal of the receptor alterations and changes in GAD. Resuscitation with oxygen alone and epinephrine was less effective in reversing the receptor alterations.
  
  
  CONCLUSIONS
  Being a source of immediate energy, glucose can reduce the ATP-depletion-induced changes in GABA and oxygenation, which helps in encountering hypoxia. The present study suggests that reduction in the GABAB receptors functional regulation during hypoxia plays an important role in central nervous system damage. Resuscitation with glucose alone and glucose and oxygen to hypoxic neonatal rats helps in protecting the brain from severe hypoxic damage.
authors.affiliation: Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin-682022 Kerala, India. biomncb@cusat.ac.in
authors.forename: Thoppil R
authors.initials: TR
authors.lastname: Anju
authors.forename: Sadanandan
authors.initials: S
authors.lastname: Jayanarayanan
authors.forename: Cheramadatikudiyil S
authors.initials: CS
authors.lastname: Paulose
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D004837:Epinephrine / Q000008:administration & dosage*; D005786:Gene Expression Regulation; D005947:Glucose / Q000008:administration & dosage*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D010100:Oxygen / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000235:genetics / Q000378:metabolism*; D012151:Resuscitation / Q000379:methods*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; D005947:Glucose; D010100:Oxygen; D004837:Epinephrine