Browsing by Author "Lee, Wei-Hua"

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    Sodium Pyruvate Reduced Hypoxic-Ischemic Injury to Neonatal Rat Brain
    (Springer Nature, 2012) Pan, Rui; Rong, Zhihui; She, Yun; Cao, Yuan; Chang, Li-Wen; Lee, Wei-Hua; Pediatrics, School of Medicine
    Background: Neonatal hypoxia-ischemia (HI) remains a major cause of severe brain damage and is often associated with high mortality and lifelong disability. Immature brains are extremely sensitive to HI, shown as prolonged mitochondrial neuronal death. Sodium pyruvate (SP), a substrate of the tricarboxylic acid cycle and an extracellular antioxidant, has been considered as a potential treatment for hypoxic-ischemic encephalopathy, but its effects have not been evaluated in appropriate animal models for hypoxic-ischemic encephalopathy. Methods: This investigation used primary cortical neuron cultures derived from neonatal rats subjected to oxygen and glucose deprivation (OGD) and a well-established neonatal rat HI model. Results: HI caused brain tissue loss and impaired sensorimotor function and spatial memory whereas SP significantly reduced brain damage and improved neurological performance. These neuroprotective effects of SP are likely the result of improved cerebral metabolism as demonstrated by maintaining adenosine triphosphate (ATP) levels and preventing an increase in intracellular reactive oxygen species (ROS) levels. SP treatment also decreased levels of Bax, a death signal for immature neurons, blocked caspase-3 activation, and activated a key survival signaling kinase, Akt, both in vitro and in vivo. Conclusion: SP protected neonatal brain from hypoxic-ischemic injury through maintaining cerebral metabolism and mitochondrial function.