alpha-Phenyl-n-tert-butyl-nitrone attenuates lipopolysaccharide-induced brain injury and improves neurological reflexes and early sensorimotor behavioral performance in juvenile rats.

Abstract

Our previous study showed that treatment with alpha-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 long-lasting 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.

• Authors: Lir-Wan Fan, Ruei-Feng Chen, Helen J Mitchell, Rick C S Lin, Kimberly L Simpson, Philip G Rhodes, Zhengwei Cai
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 86 Issue 16 Pg. 3536-47 (Dec 2008) ISSN: 1097-4547 [Electronic] United States
• PMID: 18683243 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: (c) 2008 Wiley-Liss, Inc.

Chemical References

• Cyclic N-Oxides
• Lipopolysaccharides
• Myelin Basic Protein
• Neuroprotective Agents
• phenyl-N-tert-butylnitrone

Topics

• Animals
• Animals, Newborn
• Brain (drug effects, pathology, physiopathology)
• Brain Damage, Chronic (chemically induced, drug therapy, microbiology)
• Central Nervous System Bacterial Infections (microbiology, physiopathology, transmission)
• Cyclic N-Oxides (therapeutic use)
• Disease Models, Animal
• Female
• Gait Disorders, Neurologic (chemically induced, drug therapy, microbiology)
• Humans
• Infant, Newborn
• Infectious Disease Transmission, Vertical
• Leukomalacia, Periventricular (drug therapy, microbiology)
• Lipopolysaccharides (toxicity)
• Male
• Movement Disorders (drug therapy, microbiology, physiopathology)
• Myelin Basic Protein (drug effects, metabolism)
• Nerve Fibers, Myelinated (drug effects, metabolism, pathology)
• Neuroprotective Agents (therapeutic use)
• Oligodendroglia (drug effects, metabolism, pathology)
• Pregnancy
• Rats
• Rats, Sprague-Dawley
• Recovery of Function (drug effects, physiology)
• Reflex (drug effects, physiology)