Zheng W, Perry D F, Nelson D L, Aposhian H V
Department of Pharmacology and Toxicology, University of Arizona, Tucson 86721.
FASEB J. 1991 May;5(8):2188-93. doi: 10.1096/fasebj.5.8.1850706.
Although heavy metal ions are known to be toxic to the central nervous system (CNS), the mechanisms by which the CNS may protect itself from initial challenges of such toxic ions is unknown. The choroid plexus is the principal site of formation of the cerebrospinal fluid (CSF) which bathes the brain. We have determined in rats and rabbits that after intraperitoneal administration of lead, cadmium, mercury, and arsenic compounds, these toxic metal ions accumulated in the lateral choroid plexus at concentrations of Pb, Hg, and As that were 70-, 95-, and 40-fold higher, respectively, than those found in the CSF. Cd was not detected in the CSF. In addition, concentrations of these heavy metal ions were found to be many fold greater in the choroid plexus than in the brain or blood. The accumulation of Pb in the choroid plexus was dose-dependent and time-related. When the choroid plexus was preincubated, in vitro, with ouabain (1.5 mM), the uptake of Cd from the CSF side of the choroid plexus was inhibited 57%. Cadmium metallothionein was not found in the choroid plexus. Whereas the concentration of reduced glutathione in the choroid plexus was less than that in the brain cortex, the concentration of cystine was fourfold greater. The lateral choroid plexus sequesters Pb, Cd, As, and Hg. It appears to be one of the important mechanisms that protects the CSF and the brain from the fluxes of toxic heavy metals in the blood.
尽管已知重金属离子对中枢神经系统(CNS)有毒,但CNS保护自身免受此类有毒离子初始挑战的机制尚不清楚。脉络丛是形成脑脊液(CSF)的主要部位,脑脊液会对大脑进行冲洗。我们已经在大鼠和兔子身上确定,腹腔注射铅、镉、汞和砷化合物后,这些有毒金属离子会在外侧脉络丛中蓄积,其中铅、汞和砷的浓度分别比脑脊液中的浓度高70倍、95倍和40倍。脑脊液中未检测到镉。此外,发现这些重金属离子在脉络丛中的浓度比在大脑或血液中高许多倍。铅在脉络丛中的蓄积呈剂量依赖性且与时间相关。当脉络丛在体外与哇巴因(1.5 mM)预孵育时,脉络丛脑脊液侧对镉的摄取被抑制了57%。脉络丛中未发现镉金属硫蛋白。虽然脉络丛中还原型谷胱甘肽的浓度低于大脑皮层,但胱氨酸的浓度高四倍。外侧脉络丛会隔离铅、镉、砷和汞。这似乎是保护脑脊液和大脑免受血液中有毒重金属通量影响的重要机制之一。