GENE REGULATION UNDER THE HIGH INTRACRANIAL PRESSURE

本研究旨在探讨颅内压（ICP）调节的分子生物学。研究者提出了高ICP下应激基因反应、胶质细胞功能改变和神经胶质调控基因表达等研究项目，取得了以下成果。(1)谷氨酸转运体（GLAST）基因表达与实验性脑积水：GLAST在渗透压和细胞外谷氨酸浓度的调节中起重要作用。实验性脑积水急性期，脑室周围反应性星形胶质细胞表达GLAST mRNA，高ICP和脑室扩张导致脑室周围水肿和神经元损伤。GLAST基因可能被诱导以调节局部渗透压或去除从受损轴突释放的过量谷氨酸（Masago et al.1996）。(2)ICP变化和应激基因反应使用ICP可控模型：我们在小动物（大鼠）中设计了ICP可控模型。 ...更多信息 颅内压水平由枕大池连接的滴注系统任意调节。高ICP时，大脑皮质、海马结构和下丘脑核团hsp 70 mRNA和即刻早期基因（immediate early gene，IEGs）表达上调。颅内压升高可能是对许多高级脑功能的生理应激。其中一些可能起到控制ICP变化的作用（松本等人，1995）。(3)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法建立大鼠蛛网膜下腔出血模型。SAH后，在大脑皮质、丘脑和边缘系统均有hsp 70 mRNA和IEG的表达。观察到海马CA1区神经元延迟性丢失。不仅颅内压升高，而且直接刺激蛛网膜下腔血也可引起神经元应激。(4)正在进行的项目：利用脑挫伤模型研究创伤性脑肿胀后的应激基因或凋亡基因调控。少

The present study was designed to investigate molecular biology of intracranial pressure (ICP) regulation. The investigators proposed research projects such as stress gene response, modification of glial function and osmoregulatory gene expression under the high ICP.The following results were obtained. (1) GLUTAMATE TRANSPORTER (GLAST) GENE EXPRESSION AND EXPERIMENTAL HYDROCEPHALUS : 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). (2) ICP CHANGES AND STRESS GENE RESPONSE USING ICP CONTROLLABLE MODEL : We devised ICP controllable model in small animals (rats). … More The ICP levels were arbitarily regulated by the drip infusion system connected with cisterna magna. Under the high ICP level, the upregulation of hsp 70 mRNA and immediate early genes (IEGs) was demonstrated in the cerebral cortex, hippocampal formation and hypothalamic nucleus. Increased ICP could be physiological stress to many higher brain functions. Some of them might be acting to control ICP changes (Matsumoto et al.1995). (3) SUBARACHNOID HEMORRHAGE (SAH) MODEL AND NEURONAL STRESS : We developed orginal SAH model in rats by endovascular perforation with nylon thread. This model represents closely aneurysmal SAH.After SAH,hsp 70 mRNA and IEGs were induced in the cerebral cortex, thalamus and limbic system. Delayd neuronal loss in the hippocampal CA1 was observed. Not only ICP elevation but direct stimulation of subarachnoid blood might cause neuronal stress. (4) ONGOING PROJECT : Stress gene or apoptotic gene regulation after traumatic brain swelling using contusional model is under investigation. Less