Neuroprotection of α-phenyl-n-tert-butyl-nitrone on the neonatal white matter is associated with anti-inflammation

Our previous study has demonstrated that α-phenyl-tert-butyl-nitrone (PBN) provided neuroprotection to the neonatal white matter following cerebral hypoxia-ischemia (HI). Free radical scavenging was involved in the neuroprotection of PBN. To investigate if other mechanisms contribute to the neuroprotection of PBN, postnatal day 4 SD rats were subjected to bilateral common carotid artery ligation, followed by 8% oxygen exposure for 20 min. A single dose of PBN (100 mg/kg, i.p.) was given prior to the hypoxic exposure. Expression of inflammatory cytokines: interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α) was determined by RT-PCR, ELISA and immunohistochemistry. Activation of transcriptional factor nuclear factor-kappa B (NF-κB) was measured by ELISA. PBN significantly inhibited HI-induced up-regulation of IL-1β, TNF-α and iNOS mRNA expression at 4 h following HI. PBN treatment also reduced the brain concentration of IL-1β significantly and decreased the number of IL-1β- or iNOS-expressing cells in the white matter area at 12 h following HI. Moreover, PBN suppressed the HI-induced NF-κB activation at 1 h after HI. The overall results indicate that besides free radical scavenging, anti-inflammation might partly contribute to the neuroprotection afforded by PBN on neonatal white matter following cerebral HI.