REGULATION OF CEREBROSPINAL FLUID CIRCULATION AND INTRACRANIAL PRESSURE BY WATER CHANNEL

本研究旨在探讨高颅压条件下脑脊液循环的分子调控。研究人员提出的研究项目集中在水通道、渗透压转运体和利钠肽的表达上。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到细胞内或细胞外。水通道被认为是调节脑组织中的水分含量。应用原位杂交组织化学方法，水通道(MIWC)基因在室管膜细胞和大脑白质中均有表达。但在高颅压环境和高岭土诱导的大鼠脑积水中，MIWC基因的表达无明显变化。水通道包括其他可能在病理条件下控制水含量的同源超家族。(2)C型利钠肽：C型利钠肽广泛存在于中枢神经系统，起…作用。荷尔蒙对全身血液循环的调节作用更强。脑积水后CNP基因表达无明显变化。CNP基因可能会在短时间内波动，不能得到满意的评估。(3)谷氨酸/天冬氨酸转运体(GLAST)：GLAST在渗透压和胞外谷氨酸浓度的调节中起重要作用。在实验性脑积水急性期，脑室周围反应性星形胶质细胞明显表达GLAST mRNA，急性脑积水时高颅内压和脑室扩张导致脑室周围水肿和神经元损伤。GLAST基因的诱导可能是为了调节局部渗透压或清除损伤轴突释放的过量谷氨酸(Masago等人，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的方法建立大鼠蛛网膜下腔出血模型。该模型与动脉瘤性蛛网膜下腔出血密切相关，我们正在使用该模型研究渗透调节。较少

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