Gina M Gallucci1, Ming Tong1,2, Xiaodi Chen2,3, Barbara S Stonestreet2,3, Amy Lin4, Suzanne M de la Monte1,2,4,5. 1. 1 Department of Medicine, Rhode Island Hospital, Providence, Rhode Island. 2. 2 Alpert Medical School, Brown University, Providence, Rhode Island. 3. 3 Department of Pediatrics, Women & Infants Hospital of Rhode Island, Providence, Rhode Island. 4. 4 Departments of Pathology (Neuropathology), Neurology, and Neurosurgery, Rhode Island Hospital, Providence, Rhode Island. 5. 5 Department of Pathology (Perinatal), Women & Infants Hospital of Rhode Island, Providence, Rhode Island.
Abstract
BACKGROUND: Perinatal ischemia-reperfusion (I/R) injury of cerebral white matter causes long-term cognitive and motor disabilities in children. I/R damages or kills highly metabolic immature oligodendroglia via oxidative stress, excitotoxicity, inflammation, and mitochondrial dysfunction, impairing their capacity to generate and maintain mature myelin. However, the consequences of I/R on myelin lipid composition have not been characterized. OBJECTIVE: This study utilized matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) to assess alterations in cerebral supraventricular white matter myelin lipid profiles in a fetal sheep model of perinatal I/R. METHODS: Fetal sheep (127 days gestation) were studied after 30 minutes of bilateral carotid artery occlusion followed by 4 (n = 5), 24 (n = 7), 48 (n = 3), or 72 (n = 5) hours of reperfusion, or sham treatment (n = 5). White matter lipids were analyzed by negative ion mode MALDI-MS. RESULTS: Striking I/R-associated shifts in phospholipid and sphingolipid expression occurred over the 72-hour time course with most responses detected within 4 hours of reperfusion and progressing at the 48- and 72-hour points. I/R decreased expression of phosphatidic acid and phosphatidylethanol amine and increased phosphatidylinositol, sulfatide, and lactosylceramide. CONCLUSIONS: Cerebral I/R in mid-gestation fetal sheep causes rapid shifts in white matter myelin lipid composition that may reflect injury, proliferation, or recovery of immature oligodendroglia.
BACKGROUND: Perinatal ischemia-reperfusion (I/R) injury of cerebral white matter causes long-term cognitive and motor disabilities in children. I/R damages or kills highly metabolic immature oligodendroglia via oxidative stress, excitotoxicity, inflammation, andmitochondrial dysfunction, impairing their capacity to generate and maintain mature myelin. However, the consequences of I/R on myelin lipid composition have not been characterized. OBJECTIVE: This study utilized matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) to assess alterations in cerebral supraventricular white matter myelinlipid profiles in a fetal sheep model of perinatal I/R. METHODS:Fetal sheep (127 days gestation) were studied after 30 minutes of bilateral carotid artery occlusion followed by 4 (n = 5), 24 (n = 7), 48 (n = 3), or 72 (n = 5) hours of reperfusion, or sham treatment (n = 5). White matter lipids were analyzed by negative ion mode MALDI-MS. RESULTS: Striking I/R-associated shifts in phospholipid andsphingolipid expression occurred over the 72-hour time course with most responses detected within 4 hours of reperfusion and progressing at the 48- and 72-hour points. I/R decreased expression of phosphatidic acid andphosphatidylethanol amine and increased phosphatidylinositol, sulfatide, andlactosylceramide. CONCLUSIONS:Cerebral I/R in mid-gestation fetal sheep causes rapid shifts in white matter myelin lipid composition that may reflect injury, proliferation, or recovery of immature oligodendroglia.
Entities:
Keywords:
fetal brain; ischemia reperfusion; lipidomics; mass spectrometry; sheep; white matter
Authors: Catherine Stace; Maria Manifava; Christine Delon; John Coadwell; Shamshad Cockcroft; Nicholas T Ktistakis Journal: Adv Enzyme Regul Date: 2007-11-26
Authors: Art Riddle; Ning Ling Luo; Mario Manese; Douglas J Beardsley; Lisa Green; Dawn A Rorvik; Katherine A Kelly; Clyde H Barlow; Jeffrey J Kelly; A Roger Hohimer; Stephen A Back Journal: J Neurosci Date: 2006-03-15 Impact factor: 6.167