Molecular Biological Research related to Developmental Mechanism and New Medical Treatment of Congenital Hydrocephalus

(1)我们已经在先天性脑积水htx大鼠中证明，脑积水的进展损害了前脑胆碱能系统，其完整性对学习和记忆功能至关重要。神经化学方法的结果支持了我们之前的研究结果，即先天性脑积水延迟治疗与先天性脑积水HTX大鼠的学习能力受损有关。此外，在先天性脑积水大鼠皮层中，神经生长因子（NGF）和一些在神经元存活和分化中起重要作用的细胞因子增加。神经生长因子及部分细胞因子在皮层的增加，主要依赖于在病变皮层显著出现的反应性星形胶质细胞的分泌，以及神经生长因子逆行轴突运输受损引起的积聚。(2)脑室内注射c型利钠肽（CNP）可有效降低脑脊液流出阻力和颅内压。目前的研究结果似乎表明CNP可能是治疗先天性脑积水的另一种候选药物。关于CNP的内在调控，以及其降低颅内压和脑脊液流出阻力的机制，有待进一步研究和探讨。(3)黏附分子L1基因的点突变在人类x连锁脑积水中已被证实，但在脑积水htx大鼠中未发现该点突变。我们的研究表明，脑积水htx大鼠脑内功能性c型利钠肽受体的基因表达少于Wister大鼠。这一结果提示，调节c型利钠肽受体基因的转录因子可能存在遗传异常，有待进一步研究和调查。

(1) We have demonstrated in the congenital hydrocehalic HTX-rats that the progression of hydrocephalus impaired the forebrain cholinergic system, whose integrity is essential for learning and memory functions. This result using neurochemical methods has supported our previous findings, that delayd treatment of congenital hydrocephalus was related to the impairment of learning ability in the congenital hydrocephalic HTX rats.Furthermore it was interesting that nerve growth factor (NGF) and some cytokins which play important roles in survival and differentiation of the neuron were increased in the cortex of congenital hydrocephalic HTX rats.The NGF and some cytokins increase in the cortex was supposed to depend on the secretion of reactive astrocytes prominently appearing in the affected cortex and on the accumulation due to impaired retrograde axonal transport of NGF.(2) Intraventricular injection of C-type natriuretic peptide (CNP) in hydroceohalic HTX rats was found to be effective in lowering intracranial pressure and CSF outflow resistance. The results of the present investigation would appear to suggest that CNP could be another candidate for medical treatment of congenital hydrocephalus. The problem regarding the intrinsic regulation of CNP,and the mechanism for lowering intracranial pressure and CSF outflow resistance, remain for further study and investigation.(3) The point mutation of adhesion molecule L1 gene has been demonstrated in human X-linked hydrocephalus, but we could not identify this point mutation in hydrocephalic HTX-rats. Our investigations have shown that there was less gene expression of functional C-type natriuretic peptide receptor in the brain of hydrocephalic HTX-rats than in Wister rats. This result would suggest that the transcription factor, which regulates the C-type natriuretic peptide receptor gene, may be genetically abnormal, but we need further study and investigation.