Ischemic-reperfusion (I/R) injury to cerebral white matter during the perinatal period leads to long-term cognitive and motor disabilities in children. Immature white matter oligodendrocytes are especially vulnerable to metabolic insults such as those caused by hypoxic, ischemic, and
reperfusion injury. Consequences include an impaired capacity of oligodendrocytes to generate and maintain mature
lipid-rich myelin needed for efficient neuronal conductivity. Further research is needed to increase an understanding of the early, possibly reversible myelin-associated pathologies that accompany I/R white matter injury. This experiment characterized I/R time-dependent alterations in cerebral white matter
lipid profiles in an established fetal sheep model. Fetal sheep (127 days gestation) were subjected to 30 min of bilateral carotid artery occlusion followed by 4 h (n = 5), 24 h (n = 7), 48 h (n = 3), or 72 h (n = 5) of reperfusion, or
sham treatment (n = 5). Supraventricular cerebral white matter
lipids were analyzed using the positive ionization mode matrix-assisted
laser desorption/ionization mass spectrometry. Striking I/R-associated shifts in
phospholipid (PL) and
sphingolipid expression with a prominent upregulation of
cardiolipin,
phosphatidylcholine,
phosphatidylinositol monomannoside,
sphingomyelin,
sulfatide, and ambiguous or unidentified
lipids were observed to occur mainly at I/R-48 and normalized or suppressed responses at I/R-72. In fetal sheep, cerebral I/R caused major shifts in white matter myelin
lipid composition favoring the upregulated expression of diverse PLs and
sphingolipids which are needed to support neuronal membrane, synaptic, metabolic, and cell signaling functions.