There is increasing evidence that
hyperoxia, particularly at the time of birth, may result in neurological injury, in particular to the susceptible vasculature of these tissues. This study was aimed at determining whether overexpression of extracellular
superoxide dismutase (EC-SOD) is protective against
brain injury induced by
hyperoxia. Transgenic (TG) mice (with an extra copy of the human extracellular
superoxide dismutase gene) and wild-type (WT) neonate mice were exposed to
hyperoxia (95% of F(i) o(2) ) for 7 days after birth versus the control group in room air. Brain positron emission tomography (PET) scanning with fludeoxyglucose (FDG)
isotope uptake was performed after exposure. To assess apoptosis induced by
hyperoxia exposure,
caspase 3 ELISA and
terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were performed. Quantitative western blot for the following inflammatory markers was performed:
glial fibrillary acidic protein, ionized
calcium-binding adaptor molecule 1, macrophage-inhibiting factor, and phospho-
AMP-activated protein kinase. PET scanning with FDG
isotope uptake showed significantly higher uptake in the WT
hyperoxia neonate brain group (0.14 ± 0.03) than in both the TG group (0.09 ± 0.01) and the control group (0.08 ± 0.02) (P< 0.05). Histopathological investigation showed more apoptosis and dead neurons in hippocampus and cerebellum brain sections of WT neonate mice after exposure to
hyperoxia than in TG mice; this finding was also confirmed by TUNEL staining. The
caspase 3 assay confirmed the finding of more apoptosis in WT
hyperoxia neonates (0.814 ± 0.112) than in the TG hyperoxic group (0.579 ± 0.144) (P < 0.05); this finding was also confirmed by TUNEL staining. Quantitative western blotting for the inflammatory and metabolic markers showed significantly higher expression in the WT group than in the TG and control groups. Thus, overexpression of EC-SOD in the neonate brain offers significant protection against
hyperoxia-induced brain damage.