Interleukin-1beta-induced brain injury in the neonatal rat can be ameliorated by alpha-phenyl-n-tert-butyl-nitrone.
To examine the possible role of inflammatory cytokines in mediating perinatal brain injury, we investigated effects of intracerebral injection of interleukin-1beta (IL-1beta) on brain injury in the neonatal rat and the mechanisms involved. Intracerebral administration of IL-1beta (1 microg/kg) resulted in acute brain injury, as indicated by enlargement of ventricles bilaterally, apoptotic death of oligodendrocytes (OLs) and loss of OL immunoreactivity in the neonatal rat brain. IL-1beta also induced axonal and neuronal injury in the cerebral cortex as indicated by elevated expression of beta-amyloid precursor protein, short beaded axons and dendrites, and loss of tyrosine hydroxylase-positive neurons in the substantia nigra and the ventral tegmental areas. Administration of alpha-phenyl-n-tert-butyl-nitrone (PBN, 100 mg/kg i.p.) immediately after the IL-1beta injection protected the brain from IL-1beta-induced injury. Protection of PBN was linked with the attenuated oxidative stress induced by IL-1beta, as indicated by decreased elevation of 8-isoprostane content and by the reduced number of 4-hydroxynonenal or malondialdehyde or nitrotyrosine-positive cells following IL-1beta exposure. PBN also attenuated IL-1beta-stimulated inflammatory responses as indicated by the reduced activation of microglia. The finding that IL-1beta induced perinatal brain injury was very similar to that induced by lipopolysaccharide (LPS), as we previously reported and that PBN was capable to attenuate the injury induced by either LPS or IL-1beta suggests that IL-1beta may play a critical role in mediating brain injury associated with perinatal infection/inflammation.
Fan
Lir-Wan
LW
Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS 39216-4504, USA.
Mitchell
Helen J
HJ
Tien
Lu-Tai
LT
Rhodes
Philip G
PG
Cai
Zhengwei
Z
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D001925:Brain Damage, Chronic / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D003497:Cyclic N-Oxides / Q000494:pharmacology* / Q000627:therapeutic use; D019610:Cytoprotection / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D004660:Encephalitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D005911:Gliosis / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D018836:Inflammation Mediators / Q000032:analysis / Q000378:metabolism; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009836:Oligodendroglia / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects / Q000276:immunology; D051381:Rats
D003497:Cyclic N-Oxides; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; C029217:phenyl-N-tert-butylnitrone
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