Interleukin-1beta-induced brain injury in the neonatal rat can be ameliorated by alpha-phenyl-n-tert-butyl-nitrone.
ABSTRACT 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.
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ABSTRACT: The human brain spontaneously generates neural oscillations with a large variability in frequency, amplitude, duration, and recurrence. Little, however, is known about the long-term spatiotemporal structure of the complex patterns of ongoing activity. A central unresolved issue is whether fluctuations in oscillatory activity reflect a memory of the dynamics of the system for more than a few seconds. We investigated the temporal correlations of network oscillations in the normal human brain at time scales ranging from a few seconds to several minutes. Ongoing activity during eyes-open and eyes-closed conditions was recorded with simultaneous magnetoencephalography and electroencephalography. Here we show that amplitude fluctuations of 10 and 20 Hz oscillations are correlated over thousands of oscillation cycles. Our analyses also indicated that these amplitude fluctuations obey power-law scaling behavior. The scaling exponents were highly invariant across subjects. We propose that the large variability, the long-range correlations, and the power-law scaling behavior of spontaneous oscillations find a unifying explanation within the theory of self-organized criticality, which offers a general mechanism for the emergence of correlations and complex dynamics in stochastic multiunit systems. The demonstrated scaling laws pose novel quantitative constraints on computational models of network oscillations. We argue that critical-state dynamics of spontaneous oscillations may lend neural networks capable of quick reorganization during processing demands.Journal of Neuroscience 03/2001; 21(4):1370-7. · 7.11 Impact Factor
Article: Selective vulnerability of preterm white matter to oxidative damage defined by F2-isoprostanes.[show abstract] [hide abstract]
ABSTRACT: Periventricular white matter injury (PWMI) is the leading cause of cerebral palsy and chronic neurological disability in survivors of prematurity. Despite the large number of affected children, the pathogenetic mechanisms related to PWMI remain controversial. Through studies of 33 human autopsy brains, we determined that early PWMI was related to oxidative damage that particularly targeted the oligodendrocyte lineage, whereas other neuronal and glial cell types were markedly more resistant. F(2)-isoprostanes, an arachidinate metabolite/lipid peroxidation marker of oxidative damage, were significantly increased in early PWMI lesions but not in cerebral cortex. That deleterious lipid peroxidation accompanied early PWMI was supported by similar increases in F(2)-isoprostanes levels in the cerebral cortex from term infants with hypoxic-ischemic cortical injury. Detection of F(4)-neuroprostanes, a neuronal-specific oxidative damage marker, confirmed that neuroaxonal elements were resistant to injury in cerebral cortex and white matter. Significant protein nitration was not detected in PWMI lesions by 3-nitrotyrosine staining. Significant cellular degeneration was confirmed in early PWMI lesions by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling and a marked depletion of oligodendrocyte progenitors of 71 +/- 8%. Hence, the predilection of preterm infants for PWMI is related to selective lipid peroxidation-mediated injury of cerebral white matter and targeted death of oligodendrocyte progenitors.Annals of Neurology 08/2005; 58(1):108-20. · 11.09 Impact Factor