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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.

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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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) doi:10.1177/1933719111410710

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Keywords

  • ceftriaxone
  • glutamate transporter 1 (GLT-1)
  • preconditioning
  • neuroprotection
  • neonatal rat