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Ceftriaxone Preconditioning Confers Neuroprotection in Neonatal Rats Through Glutamate Transporter 1 Upregulation

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Abstract

Objective

This study investigated the hypothesis that ceftriaxone preconditioning ameliorates brain damage in neonatal animals through glutamate transporter 1 (GLT-1) upregulation.

Study design

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. Conclusion: 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.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan

    Kazuya Mimura MD, Takuji Tomimatsu MD, Kenji Minato MS, Otgonbaatar Jugder MD, Yukiko Kinugasa-Taniguchi MD, Takeshi Kanagawa MD & Tadashi Kimura MD, PhD

  2. Department of Developmental Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Osaka, Japan

    Kazuya Mimura MD, Masatoshi Nozaki MD & Itaru Yanagihara MD, PhD

Authors
  1. Kazuya Mimura MD
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  2. Takuji Tomimatsu MD
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  3. Kenji Minato MS
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  4. Otgonbaatar Jugder MD
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  5. Yukiko Kinugasa-Taniguchi MD
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  6. Takeshi Kanagawa MD
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  7. Masatoshi Nozaki MD
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  8. Itaru Yanagihara MD, PhD
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  9. Tadashi Kimura MD, PhD
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Correspondence to Takuji Tomimatsu MD.

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Mimura, K., Tomimatsu, T., Minato, K. et al. Ceftriaxone Preconditioning Confers Neuroprotection in Neonatal Rats Through Glutamate Transporter 1 Upregulation. Reprod. Sci. 18, 1193–1201 (2011). https://doi.org/10.1177/1933719111410710

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  • DOI: https://doi.org/10.1177/1933719111410710

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