Neuroprotection of alpha-phenyl-n-tert-butyl-nitrone on the neonatal white matter is associated with anti-inflammation.
Our previous study has demonstrated that alpha-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 20min. A single dose of PBN (100mg/kg, i.p.) was given prior to the hypoxic exposure. Expression of inflammatory cytokines: interleukin-1beta (IL-1beta), inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) was determined by RT-PCR, ELISA and immunohistochemistry. Activation of transcriptional factor nuclear factor-kappa B (NF-kappaB) was measured by ELISA. PBN significantly inhibited HI-induced up-regulation of IL-1beta, TNF-alpha and iNOS mRNA expression at 4h following HI. PBN treatment also reduced the brain concentration of IL-1beta significantly and decreased the number of IL-1beta- or iNOS-expressing cells in the white matter area at 12h following HI. Moreover, PBN suppressed the HI-induced NF-kappaB activation at 1h 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.
Lin
Shuying
S
Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS 39216, United States.
Cox
Helen J
HJ
Rhodes
Philip G
PG
Cai
Zhengwei
Z
D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003497:Cyclic N-Oxides; D004797:Enzyme-Linked Immunosorbent Assay; D016166:Free Radical Scavengers / Q000494:pharmacology*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D009589:Nitrogen Oxides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D007375:Interleukin-1; D016328:NF-kappa B; D018696:Neuroprotective Agents; D009589:Nitrogen Oxides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C029217:phenyl-N-tert-butylnitrone; D052247:Nitric Oxide Synthase Type II