Tashiro Y, Drake J M, Chakrabortty S, Hattori T
Division of Neurosurgery, Hospital for Sick Children, Faculty of Medicine, University of Toronto, Ontario, Canada.
Brain Res. 1997 Oct 3;770(1-2):45-52. doi: 10.1016/s0006-8993(97)00742-7.
Structural and/or functional injury of the basal ganglia can lead to motor functional disabilities, abnormal gait and posture, and intellectual/emotional impairment, disorders also frequently seen in hydrocephalus. Previous reports have documented changes in dopamine levels in the neostriatum in experimental hydrocephalus. The present study was designed to investigate possible functional injury of cholinergic, GABAergic and dopaminergic systems in the basal ganglia immunohistochemically in a model of kaolin-induced hydrocephalus. Hydrocephalus was induced in 12 Wistar rats by intracisternal injection of 0.05 ml volume of 25% kaolin solution under microscopic guidance. Four controls received an equal volume of sterile saline. The animals were killed at 2, 4 and 8 weeks after injection. The numbers of choline acetyltransferase (ChAT)- and glutamic acid decarboxylase (GAD)-immunoreactive (IR) neostriatal neurons and tyrosine hydroxylase (TH)-IR nigral neurons, were counted in 60-micron thick representative sections and the IR cellular densities (counted cell number/neostriatal area) were calculated in the neostriatum. The number of total neostriatal neurons was also counted in 15-micron thick sections stained by cresyl violet (Nissl staining) to calculate the cellular density. The number and cellular density of neostriatal ChAT-IR neurons were significantly reduced at 2, 4, and 8 weeks after injection (P < 0.05), while those of GAD-IR neurons decreased at 4 and 8 weeks (P < 0.05). There was a linear correlation between degree of ventricular enlargement, and reduction in number of ChAT- and GAD-IR neurons (P < 0.001) as well as in the cellular density (P < 0.001). However, Nissl staining revealed no reduction in the cellular density of total neostriatal neurons (P < 0.001). TH immunoreactivity was reduced in neostriatal axons and in nigral compacta neurons, particularly in the medial portion of the dopaminergic nigrostriatal pathway. These findings suggest that progressive hydrocephalus results in functional injuries of cholinergic and GABAergic neurons in the neostriatum and dopaminergic neurons in the substantia nigra compacta by mechanical distortion. The disturbance in balance of these neurotransmitter systems in the basal ganglia may explain some of motor functional disabilities in hydrocephalus.
基底神经节的结构和/或功能损伤可导致运动功能障碍、异常步态和姿势以及智力/情感障碍，这些病症在脑积水患者中也很常见。先前的报道记录了实验性脑积水新纹状体中多巴胺水平的变化。本研究旨在通过高岭土诱导脑积水模型，免疫组织化学研究基底神经节中胆碱能、GABA能和多巴胺能系统可能存在的功能损伤。在显微镜引导下，向12只Wistar大鼠脑池内注射0.05 ml体积的25%高岭土溶液诱导脑积水。4只对照大鼠注射等量的无菌生理盐水。在注射后2、4和8周处死动物。在60微米厚的代表性切片中计数胆碱乙酰转移酶（ChAT）和谷氨酸脱羧酶（GAD）免疫反应性（IR）新纹状体神经元以及酪氨酸羟化酶（TH）-IR黑质神经元的数量，并计算新纹状体中的IR细胞密度（计数细胞数/新纹状体面积）。还用甲酚紫（尼氏染色）对15微米厚的切片进行染色，计数新纹状体神经元总数以计算细胞密度。注射后2、4和8周，新纹状体ChAT-IR神经元的数量和细胞密度显著降低（P<0.05），而GAD-IR神经元的数量在4周和8周时减少（P<0.05）。脑室扩大程度与ChAT-和GAD-IR神经元数量减少（P<0.001）以及细胞密度降低（P<0.001）之间存在线性相关性。然而，尼氏染色显示新纹状体神经元总数的细胞密度并未降低（P<0.001）。新纹状体轴突和黑质致密部神经元中的TH免疫反应性降低，尤其是在多巴胺能黑质纹状体通路的内侧部分。这些发现表明，进行性脑积水通过机械性扭曲导致新纹状体中胆碱能和GABA能神经元以及黑质致密部多巴胺能神经元的功能损伤。基底神经节中这些神经递质系统平衡的紊乱可能解释了脑积水患者的一些运动功能障碍。
