GENE REGULATION UNDER THE HIGH INTRACRANIAL PRESSURE

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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