Dexamethasone and betamethasone protect against lipopolysaccharide-induced brain damage in neonatal rats.
BACKGROUND
The aim of this study was to test whether dexamethasone (Dex) and betamethasone (Beta), two of the most commonly used corticosteroids, protect against lipopolysaccharide (LPS)-induced white matter damage and neurobehavioral dysfunction.


METHODS
LPS or sterile saline was injected into the brain white matter of rat pups at postnatal day 5 (P5), and Dex or Beta was given intraperitoneally to the rat pups 1 h before the LPS microinjection. Brain inflammatory response, brain damage, and myelination were examined at P6, P8, and P14. Neurobehavioral tests were performed from P3 through P22.


RESULTS
Our results demonstrate that Dex and Beta markedly diminish the LPS-induced brain inflammatory response, restore myelin basic protein (MBP) expression, and alleviate lateral ventricle dilation. Both corticosteroids demonstrate significant protection against most LPS-induced behavioral deficits, including those in rearing, vibrissa-elicited forelimb-placing, beam walking, learning, and elevated plus-maze test. Of note, only Beta improved the locomotion and stereotype dysfunction. In contrast to their beneficial effects, neither drug prevented LPS-induced delay in body weight gain from P6 through P21.


CONCLUSIONS
Our study suggests that if their adverse effects are minimized, corticosteroids may be the potential candidate drugs to prevent brain damage in premature infants.
Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Yi
Y
Pang
Lir-Wan
LW
Fan
Baoying
B
Zheng
Leigh R
LR
Campbell
Zhengwei
Z
Cai
Philip G
PG
Rhodes
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D001623:Betamethasone / Q000494:pharmacology*; D001930:Brain Injuries / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D003907:Dexamethasone / Q000494:pharmacology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015431:Weight Loss / Q000187:drug effects
D008070:Lipopolysaccharides; D003907:Dexamethasone; D001623:Betamethasone