Fundamental Studies to Elucidate Cerebral Developmental Impairment Mechanisms in Congenital Hydrocephalus and Development of Intrauterine Treatment.

我们对先天性脑积水的HTX大鼠进行了实验治疗，在出生后的不同时间植入了脑室-腹膜分流术(V-P分流术)，通过神经病理学和神经化学研究了这种手术的时机如何改变了神经细胞和突触发生的损害，并评估了实验动物的学习能力。1987年的实验结果表明，与非脑积水的HTX大鼠相比，推迟到出生后4周才放置V-P分流术并不能纠正皮质锥体神经元突触发生的损害和学习障碍。根据这些观察，在1988年和的实验中，更早地在出生后7天左右放置了V-P分流。通过不同的方法评价早期放置的意义，即(1)侧脑室大小和…厚度的时序性变化(2)用14C-脱氧葡萄糖放射自显影(LCGU)测量局部大脑葡萄糖利用(LCGU)；(3)神经病理学技术，包括快速高尔基染色；(4)用抗突触小泡蛋白的单抗(SVP-38,1986)免疫组织化学评价突触发生；(5)用Y臂-Maze测试观察学习能力。结果表明，早期放置V-P分流术在纠正皮质外套膜宽度减少和脑室扩大方面是明显有效的减轻脑脊液白质水肿，使室壁内室管膜细胞的形态和排列正常化，防止LCGU受损，恢复大脑锥体神经元的脊椎密度，并减少学习障碍。目前的研究似乎已经建立了一个理论基础，支持在患有先天性脑积水的动物身上早期放置V-P分流术的必要性。此外，这一结果可能会促使人们重新考虑大多数神经外科医生已经放弃的人类先天性脑积水的宫内治疗。较少

We have experimentally treated the hydrocephalus of congenitally hydrocephalic HTX-rats by inserting a ventriculoperitoneal shunt (V-P shunt), at different times after birth, investigated through neuropathology and neurochemistry clarification of how timing of such surgery modifies impairment in development of neurocytes and synaptogenesis, and assessed the learning ability of the experimental animals.Experimental results obtained in 1987 suggested that placement of the V-P shunt delayed until around 4 weeks after birth of the hydrocephalic animals did not correct impairment of synaptogenesis of cortical pyramidal neurons and learning disability in comparison with non-hydrocephalic HTX-rats. In light of such observations, earlier placement of the V-P shunt at around 7 days after birth was carried out in experiments conducted in 1988 and 1989. The significance of the early placement was evaluated by various means, i.e., (1) chronological changes in lateral ventricle size and thickness o … More f the cortical mantle of the brain by means of Isovist ventriculography and magnetic resonance imaging(MRI), (2) measurement by 14C-deoxyglucose autoradiography of local cerebral glucose utilization (LCGU), (3) neuropathological techniques including rapid Golgi staining, (4) immunohistochemical assessment of synaptogenesis using monoclonal antibodies against a synaptic vesicle protein (SVP-38 of Obata et al., 1986), and (5) observation of learning ability by means of the Y-Arm-Maze Test.The results revealed that early placement of the V-P shunt was obviously effective in correcting reduced width of the cortical mantle and dilated ventricular size, mitigating cerebrospinal fluid white matter edema, normalizing the shape and arrangement of the ependymal cells lining the ventricular walls, preventing impairment of LCGU, restoring spine density of cerebral pyramidal neurons, and in decreasing learning disability. The present investigation would appear to have established a theoretical base supporting the necessity for early placement of a V-P shunt in animals with congenital hydrocephalus.Furthermore, the results may urge reconsideration of intrauterine treatment of congenital hydrocephalus in humans which a majority of neurosurgeons already have abandoned. Less