title: Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats.
abstract: BACKGROUND
  Perinatal brain injury is the leading cause of subsequent neurological disability in both term and preterm baby. Glutamate excitotoxicity is one of the major factors involved in perinatal hypoxic-ischemic encephalopathy (HIE). Glutamate transporter GLT1, expressed mainly in mature astrocytes, is the major glutamate transporter in the brain. HIE induced excessive glutamate release which is not reuptaked by immature astrocytes may induce neuronal damage. Compounds, such as ceftriaxone, that enhance the expression of GLT1 may exert neuroprotective effect in HIE.
  
  
  METHODS
  We used a neonatal rat model of HIE by unilateral ligation of carotid artery and subsequent exposure to 8% oxygen for 2 hrs on postnatal day 7 (P7) rats. Neonatal rats were administered three dosages of an antibiotic, ceftriaxone, 48 hrs prior to experimental HIE. Neurobehavioral tests of treated rats were assessed. Brain sections from P14 rats were examined with Nissl and immunohistochemical stain, and TUNEL assay. GLT1 protein expression was evaluated by Western blot and immunohistochemistry.
  
  
  RESULTS
  Pre-treatment with 200 mg/kg ceftriaxone significantly reduced the brain injury scores and apoptotic cells in the hippocampus, restored myelination in the external capsule of P14 rats, and improved the hypoxia-ischemia induced learning and memory deficit of P23-24 rats. GLT1 expression was observed in the cortical neurons of ceftriaxone treated rats.
  
  
  CONCLUSIONS
  These results suggest that pre-treatment of infants at risk for HIE with ceftriaxone may reduce subsequent brain injury.
authors.affiliation: Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan.
authors.forename: Pei Chun
authors.initials: PC
authors.lastname: Lai
authors.forename: Yen Ta
authors.initials: YT
authors.lastname: Huang
authors.forename: Chia Chen
authors.initials: CC
authors.lastname: Wu
authors.forename: Ching-Jung
authors.initials: CJ
authors.lastname: Lai
authors.forename: Pen Jung
authors.initials: PJ
authors.lastname: Wang
authors.forename: Ted H
authors.initials: TH
authors.lastname: Chiu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western; D002443:Ceftriaxone / Q000494:pharmacology*; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000517:prevention & control; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D009483:Neuropsychological Tests; D051381:Rats
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D018698:Glutamic Acid; D002443:Ceftriaxone