Tashiro Y, Chakrabortty S, Drake J M, Hattori T
Division of Neurosurgery, Hospital for Sick Children, Toronto, Ontario, Canada.
J Neurosurg. 1997 Feb;86(2):263-71. doi: 10.3171/jns.1997.86.2.0263.
The authors investigated functional neuronal changes in experimental hydrocephalus using immunohistochemical techniques for glutamic acid decarboxylase (GAD) and two neuronal calcium-binding proteins: parvalbumin (PV) and calbindin D28K (CaBP). Hydrocephalus was induced in 16 adult Wistar rats by intracisternal injection of a kaolin solution, which was confirmed microscopically via atlantooccipital dural puncture. Four control rats received the same volume of sterile saline. Immunohistochemical staining for GAD, PV, and CaBP, and Nissl staining were performed at 1, 2, 3, and 4 weeks after the injection. Hydrocephalus occurred in 90% of kaolin-injected animals with various degrees of ventricular dilation. In the cerebral cortex, GAD-, PV-, and CaBP-immunoreactive (IR) interneurons initially lost their stained processes together with a concomitant loss of homogeneous neuropil staining, followed by the reduction of their total number. With progressive ventricular dilation, GAD- and PV-IR axon terminals on the cortical pyramidal cells disappeared, whereas the number of CaBP-IR pyramidal cells decreased, and ultimately in the most severe cases of hydrocephalus, GAD, PV, and CaBP immunoreactivity were almost entirely diminished. In the hippocampus, GAD-, PV-, and CaBP-IR interneurons demonstrated a reduction of their processes and terminals surrounding the pyramidal cells, with secondary reduction of CaBP-IR pyramidal and granular cells. On the other hand, Nissl staining revealed almost no morphological changes induced by ischemia or neuronal degeneration even in the most severe cases of hydrocephalus. Hydrocephalus results in the progressive functional impairment of GAD-, PV-, and CaBP-IR neuronal systems in the cerebral cortex and hippocampus, often before there is evidence of morphological injury. The initial injury of cortical and hippocampal interneurons suggests that the functional deafferentation from intrinsic projection fibers may be the initial neuronal event in hydrocephalic brain injury. Although the mechanism of this impairment is still speculative, these findings emphasize the importance of investigating the neuronal pathophysiology in hydrocephalus.
作者使用谷氨酸脱羧酶（GAD）以及两种神经元钙结合蛋白：小白蛋白（PV）和钙结合蛋白D28K（CaBP）的免疫组织化学技术，研究了实验性脑积水时神经元的功能变化。通过脑池内注射高岭土溶液在16只成年Wistar大鼠中诱导脑积水，通过寰枕硬膜穿刺在显微镜下证实。4只对照大鼠接受相同体积的无菌生理盐水。在注射后1、2、3和4周进行GAD、PV和CaBP的免疫组织化学染色以及尼氏染色。90%注射高岭土的动物发生脑积水，伴有不同程度的脑室扩张。在大脑皮层，GAD、PV和CaBP免疫反应性（IR）中间神经元最初失去其染色的突起，同时均匀的神经毡染色也随之丧失，随后其总数减少。随着脑室扩张的进展，皮质锥体细胞上的GAD和PV-IR轴突终末消失，而CaBP-IR锥体细胞数量减少，最终在最严重的脑积水病例中，GAD、PV和CaBP免疫反应性几乎完全消失。在海马体中，GAD、PV和CaBP-IR中间神经元围绕锥体细胞的突起和终末减少，CaBP-IR锥体细胞和颗粒细胞继发性减少。另一方面，即使在最严重的脑积水病例中，尼氏染色显示几乎没有因缺血或神经元变性引起的形态学变化。脑积水导致大脑皮层和海马体中GAD、PV和CaBP-IR神经元系统的渐进性功能损害，通常在有形态学损伤证据之前就已出现。皮质和海马体中间神经元的初始损伤表明，来自内在投射纤维的功能性传入缺失可能是脑积水脑损伤中的初始神经元事件。尽管这种损害的机制仍属推测，但这些发现强调了研究脑积水神经元病理生理学的重要性。
