Aono Mitsuo, Lee Yoonki, Grant Elfrida R, Zivin Robert A, Pearlstein Robert D, Warner David S, Bennett Ellen R, Laskowitz Daniel T
Multidisciplinary Neuroprotection Laboratory, Duke University Medical Center, Durham, North Carolina 27710, USA.
Neurobiol Dis. 2002 Oct;11(1):214-20. doi: 10.1006/nbdi.2002.0541.
Preclinical and clinical evidence implicates a role for endogenous apolipoprotein E in modifying the response of the brain to focal and global ischemia. To investigate whether apoE modulates the neuronal response to glutamate excitotoxicity, we exposed primary neuronal glial cultures and a neuronal cell line to biologically relevant concentrations of apolipoprotein E prior to NMDA exposure. In both of these paradigms, apolipoprotein E exerted partial protective effects. At neuroprotective concentrations, however, apolipoprotein E failed to block NMDA-induced calcium influx to the same magnitude as the NMDA receptor antagonist MK-801. These results suggest that one mechanism by which apolipoprotein E modifies the central nervous system response to ischemia may be by reducing glutamate-induced excitotoxicity.
临床前和临床证据表明内源性载脂蛋白E在改变大脑对局灶性和全身性缺血的反应中发挥作用。为了研究载脂蛋白E是否调节神经元对谷氨酸兴奋性毒性的反应，我们在暴露于N-甲基-D-天冬氨酸（NMDA）之前，将原代神经胶质细胞培养物和一种神经元细胞系暴露于具有生物学相关性浓度的载脂蛋白E中。在这两种实验模式中，载脂蛋白E均发挥了部分保护作用。然而，在神经保护浓度下，载脂蛋白E未能像NMDA受体拮抗剂MK-801那样同等程度地阻断NMDA诱导的钙内流。这些结果表明，载脂蛋白E改变中枢神经系统对缺血反应的一种机制可能是通过减轻谷氨酸诱导的兴奋性毒性。
