Critical Shifts in Cerebral White Matter Lipid Profiles After Ischemic-Reperfusion Brain Injury in Fetal Sheep as Demonstrated by the Positive Ion Mode MALDI-Mass Spectrometry.
Critical Shifts in Cerebral White Matter Lipid Profiles After Ischemic-Reperfusion Brain Injury in Fetal Sheep as Demonstrated by the Positive Ion Mode MALDI-Mass Spectrometry.
复制标题
DOI：
10.1177/2155179019897002
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Stonestreet BS
中科院分区：
文献类型：
--
作者：
de la Monte SM;Gallucci GM;Lin A;Tong M;Chen X;Stonestreet BS
围产期脑白色物质的缺血再灌注（I/R）损伤导致儿童长期的认知和运动障碍。未成熟的白色少突胶质细胞特别容易受到代谢损伤，例如由缺氧、缺血和再灌注损伤引起的损伤。其后果包括少突胶质细胞产生和维持有效神经元传导所需的成熟富脂髓鞘的能力受损。需要进一步的研究来增加对伴随I/R白色物质损伤的早期、可能可逆的髓鞘相关病理的理解。本实验在已建立的胎羊模型中表征了脑白色物质脂质谱的I/R时间依赖性改变。对胎羊（妊娠127天）进行30分钟的双侧颈动脉闭塞，然后进行4小时（n = 5）、24小时（n = 7）、48小时（n = 3）或72小时（n = 5）的再灌注或假处理（n = 5）。采用正离子模式基质辅助激光解吸/电离质谱分析室上性脑白色脂质。观察到磷脂（PL）和鞘脂表达的显著I/R相关变化，以及心磷脂、磷脂酰胆碱、磷脂酰肌醇单甘露糖苷、鞘磷脂、硫苷脂和模糊或未识别脂质的显著上调主要发生在I/R-48，并在I/R-72恢复正常或抑制反应。在胎羊中，脑I/R引起白色物质髓鞘脂质组成的重大变化，有利于支持神经元膜、突触、代谢和细胞信号传导功能所需的各种PL和鞘脂的表达上调。
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.