Dexamethasone induces neurodegeneration but also up-regulates vascular endothelial growth factor A in neonatal rat brains

• Published in: Neuroscience Vol. 158; no. 2; pp. 823 - 832
• Main Authors: Feng, Y, Rhodes, P.G, Liu, H, Bhatt, A.J
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 23-01-2009; Elsevier
• Subjects: Age Factors; Animals; Animals, Newborn; Biological and medical sciences; Body Weight - drug effects; Brain - drug effects; Caspase 3 - metabolism; corticosterone; Dexamethasone - pharmacology; Dose-Response Relationship, Drug; Female; Fundamental and applied biological sciences. Psychology; glucocorticoids; Glucocorticoids - pharmacology; Male; Neurogenesis - drug effects; Neurology; neurotoxicity; neurotrophins; newborn rat; Organ Size - drug effects; Pregnancy; premature infant; Rats; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Up-Regulation - drug effects; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Vertebrates: nervous system and sense organs; HLF; DexRD; basic fibroblast growth factor; SGZ; dexamethasone single dose; DexTD; neurotoxicity; newborn rat; nerve growth factor; RT- PCR; GCs; C t; postnatal day; glucocorticoids; glyceraldehyde-3-phosphate dehydrogenase; neurotrophins; dexamethasone repeated doses; phosphatidylinositol 3-kinase; dexamethasone; dexamethasone tapering doses; DexSD; VEGF; cycle threshold; PI 3; subgranular zone; HIF-1 like factor; NGF; bFGF; premature infant; PD; Dex; enzyme-linked immunosorbent assay; reverse transcription polymerase chain reaction; corticosterone; GAPDH; vascular endothelial growth factor A; ELISA; Ct; Neurotrophin; Dexamethasone; Rat; Corticosterone; Rodentia; Central nervous system; Glucocorticoid; Encephalon; Vertebrata; Neurotoxicity; Mammalia; Vascular endothelium growth factor; Animal; Adrenal hormone; Degeneration
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2008.10.024

Abstract 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 VEGF164 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 (VEGF120 , VEGF164 , and VEGF188 ) 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 VEGF164 and VEGF188 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.