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Research

Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats

Pei C Lai^1,2, Yen T Huang^1,3,6, Chia C Wu⁴, Ching-Jung Lai⁵, Pen J Wang² and Ted H Chiu^1,6*

• * Corresponding author: Ted H Chiu thchiu@mail.tcu.edu.tw

Author Affiliations

¹ Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan

² Department of Pediatrics, Buddhist Tzu Chi General Hospital, Hualien, Taiwan

³ Division of Surgical Critical Care Unit, Buddhist Tzu Chi General Hospital, Hualien, Taiwan

⁴ Department of Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan

⁵ Department of Physiology, Tzu Chi University, Hualien, Taiwan

⁶ Department of Pharmacology, Tzu Chi University, Hualien, Taiwan

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Journal of Biomedical Science 2011, 18:69 doi:10.1186/1423-0127-18-69

Published: 21 September 2011

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.

Conclusion

These results suggest that pre-treatment of infants at risk for HIE with ceftriaxone may reduce subsequent brain injury.