REGULATION OF CEREBROSPINAL FLUID CIRCULATION AND INTRACRANIAL PRESSURE BY WATER CHANNEL

本研究旨在探讨高颅内压下脑脊液循环的分子调控。研究人员提出了水通道、渗透转运蛋白和利钠肽表达的研究方向。得到了以下结果：(1)水通道基因的表达：水通道通过细胞膜将水分子输送进出细胞。水通道被认为是调节脑组织中的水分含量。采用原位杂交组织化学方法，在室管膜细胞和脑白质中表达水通道（MIWC） mRNA。然而，在高颅内压环境和高岭土诱导的脑积水大鼠中，MIWC mRNA的表达没有变化。在病理条件下，水通道还包括其他可能控制水分含量的同源超家族。(2) c型利钠肽（C-TYPE NATRIURETIC PEPTIDE， CNP）： CNP广泛存在于中枢神经系统，在激素调节全身血液循环中起重要作用。脑积水发生后，cnpmrna的表达无明显变化。CNP基因可能在短时间内波动，不能令人满意地评估。(3)谷氨酸/天冬氨酸转运蛋白（GLAST）： GLAST在调节渗透压和细胞外谷氨酸浓度中起重要作用。在实验性脑积水急性期，脑室周围反应性星形胶质细胞显著表达GLAST mRNA。急性脑积水的高颅内压和脑室扩张可引起脑室周围水肿和神经元损伤。诱导GLAST基因可能是为了调节局部渗透压或清除受损轴突释放的过量谷氨酸（Masago et al.1996）。(4)蛛网膜下腔出血（SAH）模型与神经元应激：采用尼龙线血管内穿孔建立大鼠原始SAH模型。该模型与动脉瘤性SAH密切相关。我们正在使用这种SAH模型研究渗透调节。少

The present study was designed to investigate molecular regulation of cerebrospinal fluid circulation under the high intracranial pressure. The investigators proposed research projects focused on the expression of water channel, osmolyte transporters and natriuretic peptide. The following results were obtained. (1)EXPRESSION OF WATER CHANNEL GENE : Water channel transports water molecules across the cell membrane into or out of the cells. Water channel is supposed to regulate water content in the brain tissue. Using in situ hybridization histochemistry, water channel (MIWC) mRNA was expressed in the ependymal cells and cerebral white matter. However, MIWC mRNA expression did not change in the high intracranial environment and kaoline-induced hydrocephalus in rats. Water channel includes other homologous superfamilies which might control water content in the pathological conditions. (2)C-TYPE NATRIURETIC PEPTIDE (CNP) : CNP is widely present over the central nervous system and plays a r … More ole in the hormonal regulation of systemic blood circulation. The expression of CNP mRNA was changeless after the development of hydrocephalus. The CNP gene might fluctuate within a short period and could not be evaluated satisfactorily. (3)GLUTAMATE/ASPARTATE TRANSPORTER (GLAST) : GLAST plays an important role in regulation of osmotic pressure and extracellular glutamate concentration. In the acute stage of experimental hydrocephalus, periventricular reactive astrocytes markedly expressed GLAST mRNA.High ICP and ventricular dilatation in the acute hydrocephalus cause periventricular edema and neuronal damage. GLAST gene might be induced in order to regulate local osmotic pressure or remove excess glutamate released from injured axons (Masago et al.1996). (4)SUBARACHNOID HEMORRHAGE (SAH) MODEL AND NEURONAL STRESS : We developed original SAH model in rats by endovascular perforation with nylon thread. This model represents closely aneurysmal SAH.We are investigating osmoregulation using this SAH model. Less