Dexamethasone induces neurodegeneration but also up-regulates vascular endothelial growth factor A in neonatal rat brains.
The use of dexamethasone (Dex) in premature infants to prevent and/or treat bronchopulmonary dysplasia can adversely affect early neurodevelopment and probably result in loss of cerebral volume. Vascular endothelial growth factor A (VEGF), specifically VEGF(164) isoform has neurotrophic, neuroprotective and neurogenesis enhancing effects. Previous studies have demonstrated that Dex usually down-regulates VEGF. In the present study we investigated the effect of Dex on brain growth and VEGF in the neonatal rat brain. The pups in each litter were divided into the vehicle (n=84) or Dex-treated (n=98) groups. Rat pups in the Dex group received one of three different regimens of i.p. Dex which included tapering doses on postnatal days 3-6 (0.5, 0.25, 0.125 and 0.06 mg/kg, respectively), or repeated doses of 0.5 or 1 mg/kg/day on postnatal days 4-6 or single dose of 0.031, 0.06, 0.125, 0.25 or 0.5 mg/kg on postnatal day 6. The total VEGF protein and mRNA expression of the three main VEGF splice variants (VEGF(120), VEGF(164), and VEGF(188)) were measured in the rat pup brain using enzyme-linked immunosorbent assay and real-time reverse transcription polymerase chain reaction, respectively. Treatment with Dex significantly decreased the gain of body and brain weight. The tapering and repeated doses of Dex significantly increased caspase-3 activity, VEGF protein and the expression of mRNA of VEGF(164) and VEGF(188) splice variants but the single dose did not. We conclude that Dex is neurodegenerative in the developing brain but also increases VEGF which may play a neurotrophic and neuroprotective role.
Feng
Y
Y
Division of Newborn Medicine, Department of Pediatrics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA.
Rhodes
P G
PG
Liu
H
H
Bhatt
A J
AJ
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D008297:Male; D055495:Neurogenesis / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D005938:Glucocorticoids; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D003907:Dexamethasone; D053148:Caspase 3