Journal
EXPERIMENTAL NEUROLOGY
Volume 220, Issue 1, Pages 143-153Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2009.08.003
Keywords
alpha-Phenyl-n-tert-butyl-nitrone; Interleukin-1 beta; Brain injury; Microglial activation; Oxidative stress
Categories
Funding
- NIH [HD 35496, NS 54278]
- Newborn Medicine Funds
- Department of Pediatrics, UMC, Jackson, MS, USA
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To examine the possible role of inflammatory cytokines in mediating perinatal brain injury, we investigated effects of intracerebral injection of interleukin-1 beta (IL-1 beta) on brain injury in the neonatal rat and the mechanisms involved. Intracerebral administration of IL-1 beta (1 mu g/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-1 beta 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-1 beta injection protected the brain from IL-1 beta-induced injury. Protection of PBN was linked with the attenuated oxidative stress induced by IL-1 beta, 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-1 beta exposure. PBN also attenuated IL-1 beta-stimulated inflammatory responses as indicated by the reduced activation of microglia. The finding that IL-1 beta 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-1 beta suggests that IL-1 beta may play a critical role in mediating brain injury associated with perinatal infection/inflammation. (C) 2009 Elsevier Inc. All rights reserved.
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