Kustova Y, Grinberg A, Basile A S
Laboratory of Bio-Organic Chemistry, Building 8, Room 1A15, NIDDK, NICHD, National Institutes of Health, Bethesda, MD 20892-0008, USA.
Brain Res. 1999 Aug 21;839(1):153-63. doi: 10.1016/s0006-8993(99)01734-5.
Serum protein levels in LP-BM5 infected mouse brains were investigated to gain insight into the contribution of blood-brain barrier (BBB) patency to the pathogenesis of retroviral encephalopathy. Evans blue uptake by the forebrain and cerebellum was significantly increased between 8-12 weeks post inoculation. Immunohistochemistry revealed foci of albumin, transferrin, alpha(2)-macroglobulin and IgG transudation around blood vessels particularly in the cerebral cortex and cerebellar vermis. These leaks were often associated with astrocytosis and apoptotic cells. Unlike the other serum proteins, IgG immunoreactivity extended from the circumventricular organs and disseminated throughout the brain parenchyma, accumulating on the plasma membranes of hippocampal and cortical neurons. Consistent with the chronic elevation of free glutamate levels in LP-BM5 infected mice, the increase in Evans blue uptake into the forebrain was completely reversed following dizocilpine administration. Thus, the chronic increase in free glutamate levels in LP-BM5 infected mouse brain contributes to BBB disruption. Furthermore, the CNS accumulation of serum proteins, particularly IgG, observed in these mice may increase osmotic load, impair neuronal function, and cause white matter pallor. Administration of NMDA receptor antagonists may prove useful in managing BBB permeability in those neuropathologies, such as HIV-associated dementia/cognitive/motor complex, having a glutamatergic component.
研究了感染LP - BM5的小鼠大脑中的血清蛋白水平，以深入了解血脑屏障（BBB）通透性在逆转录病毒脑病发病机制中的作用。接种后8 - 12周，前脑和小脑对伊文思蓝的摄取显著增加。免疫组织化学显示，血管周围存在白蛋白、转铁蛋白、α(2)-巨球蛋白和IgG渗出灶，尤其是在大脑皮层和小脑蚓部。这些渗漏常与星形细胞增生和凋亡细胞有关。与其他血清蛋白不同，IgG免疫反应性从室周器官延伸并扩散到整个脑实质，积聚在海马和皮层神经元的质膜上。与LP - BM5感染小鼠中游离谷氨酸水平的慢性升高一致，给予地佐环平后，前脑对伊文思蓝摄取的增加完全逆转。因此，LP - BM5感染小鼠大脑中游离谷氨酸水平的慢性升高导致血脑屏障破坏。此外，在这些小鼠中观察到的血清蛋白，尤其是IgG在中枢神经系统的积聚，可能会增加渗透压负荷，损害神经元功能，并导致白质苍白。在那些具有谷氨酸能成分的神经病理学疾病，如HIV相关痴呆/认知/运动复合体中，给予NMDA受体拮抗剂可能对控制血脑屏障通透性有用。
