Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats

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.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.These results suggest that pre-treatment of infants at risk for HIE with ceftriaxone may reduce subsequent brain injury.Perinatal hypoxia and ischemia cause serious complications [1]. 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. The pathophysiology of HIE includes energy failure, intracellular calcium accumulation, glutamate and nitric oxide neurotoxicity, lipid peroxidation, free radical formation, and inflammation [3,4]. As the survival rate of premature infants increased since 1990s, increased risk of significant neurodevelopmental impairment was also noted [5]. Intervention strategies to HIE include hypothermia and erythropoietin therapy, which reduce neurological damage in animal models of HIE [3]. In recent human studies, therapeutic hypothermia demonstrated a significant reduction of the risk of death and neurological impairment at 18 months of age [6]. But, there was no significant difference