�\-Phenyl-n-tert-butyl-nitrone attenuates lipopolysaccharide-induced brain injury and improves neurological reflexes and early sensorimotor behavioral performance in juvenile rats
Resource
Journal of Neuroscience Research 86 (16): 3536-3547
Journal
Journal of Neuroscience Research
Journal Volume
86
Journal Issue
16
Pages
3536-3547
Date Issued
2008
Date
2008
Author(s)
Fan, Lir-Wan
Mitchell, Helen J.
Lin, Rick C. S.
Simpson, Kimberly L.
Rhodes, Philip G.
Cai, Zhengwei
Abstract
Our previous study showed that treatment with α-phenyl-n-tert-butyl-nitrone (PBN) after exposure to lipopolysaccharide (LPS) reduced LPS-induced white matter injury in the neonatal rat brain. The object of the current study was to further examine whether PBN has longlasting protective effects and ameliorates LPS-induced neurological dysfunction. Intracerebral (i.c.) injection of LPS (1 mg/kg) was performed in postnatal day (P) 5 Sprague Dawley rat pups and PBN (100 mg/kg) or saline was administered intraperitoneally 5 min after LPS injection. The control rats were injected (i.c.) with sterile saline. Neurobehavioral tests were carried out from P3 to P21, and brain injury was examined after these tests. LPS exposure resulted in severe brain damage, including enlargement of ventricles bilaterally, loss of mature oligodendrocytes, impaired myelination as indicated by the decrease in myelin basic protein immunostaining, and alterations in dendritic processes in the cortical gray matter of the parietal cortex. Electron microscopic examination showed that LPS exposure caused impaired myelination as indicated by the disintegrated myelin sheaths in the juvenile rat brain. LPS administration also significantly affected neurobehavioral functions such as performance in righting reflex, wire hanging maneuver, cliff avoidance, negative geotaxis, vibrissa-elicited forelimb-placing test, beam walking, and gait test. Treatment with PBN, a free radical scavenger and antioxidant, provided protection against LPS-induced brain injury and associated neurological dysfunction in juvenile rats, suggesting that antioxidation might be an effective approach for therapeutic treatment of neonatal brain injury induced by infection/inflammation. ? 2008 Wiley-Liss, Inc.
Subjects
Antioxidant; Impaired myelination; Lipopolysaccharide; Neurobehavioral performance; White matter injury
SDGs
Other Subjects
lipopolysaccharide; myelin basic protein; n tert butyl alpha phenylnitrone; animal experiment; animal model; animal tissue; antioxidant activity; article; brain damage; brain injury; brain ventricle dilatation; controlled study; demyelination; electron microscopy; gait; gray matter; immunohistochemistry; injury severity; juvenile animal; myelin sheath; neuroprotection; newborn; newborn infection; nonhuman; oligodendroglia; parietal lobe; priority journal; psychomotor performance; rat; reflex; righting reflex; sensorimotor function; Sprague Dawley rat; Animals; Animals, Newborn; Brain; Brain Damage, Chronic; Central Nervous System Bacterial Infections; Cyclic N-Oxides; Disease Models, Animal; Female; Gait Disorders, Neurologic; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Leukomalacia, Periventricular; Lipopolysaccharides; Male; Movement Disorders; Myelin Basic Proteins; Nerve Fibers, Myelinated; Neuroprotective Agents; Oligodendroglia; Pregnancy; Rats; Rats, Sprague-Dawley; Recovery of Function; Reflex
Type
journal article