α-Phenyl-n-tert-butyl-nitrone ameliorates hippocampal injury and improves learning and memory in juvenile rats following neonatal exposure to lipopolysaccharide

• Published in: The European journal of neuroscience 2008-03, Vol.27 (6), p.1475-1484
• Main Authors: Fan, Lir-Wan, Tien, Lu-Tai, Mitchell, Helen J., Rhodes, Philip G., Cai, Zhengwei
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; axonal injury; Brain Injuries - chemically induced; Brain Injuries - pathology; Brain Injuries - prevention & control; cognitive deficits; Cyclic N-Oxides - therapeutic use; Female; hippocampus; Hippocampus - drug effects; Hippocampus - pathology; Learning - drug effects; Learning - physiology; Lipopolysaccharides - toxicity; Male; Memory - drug effects; Memory - physiology; Motor Activity - drug effects; Motor Activity - physiology; Neuroprotective Agents - therapeutic use; Pregnancy; Rats; Rats, Sprague-Dawley; substantia nigra; tyrosine hydroxylase
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/j.1460-9568.2008.06121.x

Neonatal exposure to infectious agents may result in long‐term neurological disability, and is particularly associated with the subsequent development of motor and cognitive disturbances. Our previous studies have shown that treatment with α‐phenyl‐n‐tert‐butyl‐nitrone (PBN) following exposure to lipopolysaccharide (LPS) reduces LPS‐induced brain injury in the neonatal rat. To examine whether PBN has long‐lasting protective effects and ameliorates LPS‐induced motor and cognitive dysfunction, PBN (100 mg/kg) was administered intraperitoneally 5 min after an LPS (1 mg/kg) intracerebral injection in postnatal day 5 (P5) Sprague–Dawley rat pups. Neurobehavioral tests were carried out from P3 to P21, and brain injury was examined at 24 h and 16 days after LPS injection. Neonatal LPS exposure resulted in hyperactivity from P13 to P17 in the open field task as compared with the control rat. Neurobehavioral deficits that were still observable at P21 included dysfunction in the beam‐walking and pole tests, learning and memory deficits in the passive avoidance task, and less anxiety‐like response in the elevated plus‐maze task. These behavioral findings were matched by LPS‐induced axonal injury in the CA1 region of the middle dorsal hippocampus (HP), reduction in the size of the HP and the number of neurons in the CA1 region of the middle dorsal HP, and loss of tyrosine hydroxylase immunoreactivity in neurons in the substantia nigra and ventral tegmental areas. Treatment with PBN provided long‐lasting protection against the LPS‐induced axonal injury and neuronal loss, and improved the associated neurological dysfunctions in juvenile rats.