Effects of environmental stresses on the permeability of blood brain barrier

2，3，7，8-四氯二苯并对二恶英(TCDD)被认为是最有效的环境内分泌干扰物之一。TCDD已被证明是一种强大的致癌物质，并具有免疫毒性作用。然而，二恶英是否对中枢神经系统也有毒性，目前还不确定。本研究旨在探讨亚慢性染毒对雄性Wistar大鼠中枢神经系统的毒性作用。从8周龄到28周龄，灌胃给予TCDD(1μg/kg/周)，测定大鼠的运动能力、摄食量和饮水量。与赋形剂对照组相比，服用TCDD的大鼠从给药后4周开始体重增加显著减少。在12小时光照/黑暗条件下，TCDD治疗组大鼠在所有实验时段都表现出较高的运动活动，且在治疗后16-20周有统计学意义，且不改变昼夜节律。食物和水的摄入量在两组之间没有差异。这些结果表明，TCDD可能影响中枢神经系统发生多动，即使在成年。我们进一步研究了应激对血脑屏障(BBB)通透性的影响。将大鼠分为3组，即心理应激组、生理应激组和对照组。通过测定脑组织中伊文思蓝的浓度来检测血脑屏障的通透性。应激负荷增加了大脑皮层伊文思蓝的浓度。这种影响在心理压力组中更为明显。在海马区，两种压力都会增加伊文思蓝的浓度。这些结果表明，在应激条件下，TCDD诱导的大鼠多动可能更加明显。

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is considered to be one of the most potent environmental endocrine disruptors. TCDD has been demonstrated to be a potent carcinogen and have immunotoxic effects. It is still uncertain, however, whether dioxins have also toxic properties in the central nervous system. The present study was designed to investigate the toxicity of the subchronic treatment of TCDD in the central nervous system of male Wistar rats. Rats were received oral administrations of TCDD (1μg/kg/week) from 8 weeks-old to 28 weeks-old, and the locomotor activities, food consumption and water intakes were measured. The TCDD-treated rats were significantly reduced in the gains of body weight from 4 weeks after the administration, compared to vehicle-controls. Under 12 hour-light/dark condition, the TCDD-treated rats exhibited higher locomotor activities in all experimental periods, and that was statistically significant at 16-20 weeks after the treatment, without altering circadian rhythm. Food and water intakes were not different between the groups. These results suggest that TCDD may affect in a central nervous system to occur hyperactivity in rats even in adulthood.We examined, furthermore, the effects of stress on the permeability of blood brain barrier (BBB) using a communication box method. Rats were divided into three groups, namely, psychological stress, physical stress and control group. Permeability of BBB was examined by measuring the concentration of evans blue administered I.V., in the brain tissues. A load of stress increased the concentration of evans blue in cerebral cortex. This effect was more potent in a psychological stress group. In the hippocampus, both stresses also intend to increase the concentration of evans blue. These results suggest that TCDD induced hyperactivity in rat may more evident in case of stressful conditions.