title: Ceftriaxone preconditioning confers neuroprotection in neonatal rats through glutamate transporter 1 upregulation.
abstract: OBJECTIVE
  This study investigated the hypothesis that ceftriaxone preconditioning ameliorates brain damage in neonatal animals through glutamate transporter 1 (GLT-1) upregulation.
  
  
  METHODS
  Sprague Dawley rats were pretreated with ceftriaxone, erythromycin, minocycline, or saline for 5 consecutive days starting from postnatal day 2 (P2), and GLT-1/glutamate-aspartate transporter (GLAST) messenger RNA (mRNA) and protein levels were examined in the P7 brains. After ceftriaxone or saline preconditioning, the P7 rats underwent hypoxic-ischemic (H-I) procedure or sham operation. One week after the procedure (P14), hematoxylin-eosin staining, microtubule-associated protein 2 (MAP-2) immunostaining, and transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay were used to examine neuronal damage and possible neurotoxicity.
  
  
  RESULTS
  Repeated ceftriaxone injections significantly increased GLT-1 mRNA and protein levels but not GLAST. Following such treatment and H-I procedure, the MAP-2-positive area increased and TUNEL-positive cells decreased.
  
  
  CONCLUSIONS
  Antenatal ceftriaxone may help to provide neuroprotection in the immature brain and become a new prophylactic strategy to reduce neonatal encephalopathy in clinical perinatal medicine.
authors.affiliation: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Mimura
authors.forename: Takuji
authors.initials: T
authors.lastname: Tomimatsu
authors.forename: Kenji
authors.initials: K
authors.lastname: Minato
authors.forename: Otgonbaatar
authors.initials: O
authors.lastname: Jugder
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kinugasa-Taniguchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kanagawa
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nozaki
authors.forename: Itaru
authors.initials: I
authors.lastname: Yanagihara
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kimura
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002443:Ceftriaxone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D027341:Excitatory Amino Acid Transporter 1 / Q000187:drug effects / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D012333:RNA, Messenger; C493395:Slc1a2 protein, rat; C493392:Slc1a3 protein, rat; D002443:Ceftriaxone