Abstract
BackgroundPerinatal 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.MethodsWe 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.ResultsPre-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.ConclusionThese results suggest that pre-treatment of infants at risk for HIE with ceftriaxone may reduce subsequent brain injury.
Highlights
Perinatal brain injury is the leading cause of subsequent neurological disability in both term and preterm baby
Our results indicate that pretreatment with ceftriaxone in neonatal rats can reverse hypoxic-ischemic induced morphological and functional alterations
The rat pups were returned to home cage with their dam for 1 hr followed by exposure to hypoxia (92% N2 + 8% O2) for 2 hrs by placing them in an airtight chamber partially submersed in a 37°C water bath
Summary
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. Preterm and sick infants are at high risk for brain injury and neurodevelopmental problems [2]. The hypoxia and ischemia induced brain injury in neonates is defined as hypoxic-ischemic encephalopathy (HIE) which is the leading cause of neurological sequelae in premature infants.
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