Molecular research for developmental mechanism and gene therapy for hydrocephalus

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The natriuretic peptides are hormones that stimulate natriuretic, diuretic and vasorelaxant activity. C-type natriuretic peptide (CNP), a newly identified member of the natriuretic peptide family, is thought to function mainly as a neuropeptide. With this mind, we conducted a test to determine whether CNP could control the electrolytes homeostasis and water content in the central nerve system. Four experimental investigations were carried out. (1) intracellular cGMP concentration using immunoenzyme assay in primary astrocytes and glioma U373 cells in response to CNP.(2) Cell size in glioma U373 cells with and without Guanylate Cyclase-B receptor (GC-B) cDNA in response to CNP.(3) Changes in intracranial pressure in congenital hydrocephalic HTX-rats (HTX) after bolus intraventricular CNP injection were measured. (4) CNP concentration in HTX CSF were measured by radioimmunoassay for CNP.The following results were obtained. (1) cGMP production in cultured astrocytes was found to be dependent on the concentrations of CNP added to the culture media. (2) CNP treatment results in gradual decrease of the cell size in U373 with GC-B receptor that starts 5 mm. after treatment and reaches the maximum after 30 mm.(3)Intraventricular injection of CINIP in HTX was found to be effective in lowering intracranial pressure. (4) CNP concentration of CSF collected from HTX with no disturbance of CSF circulation were 4.82 * 2.68 pg/ml and, while CNP concentration of hydrocephalic HTX were 17.34 * 4.04 pg/ml. These results suggest that CNP regulates ion and water transport via CC-B receptor in astrocytes. Since astrocytes are involved in the volume and ion control in the central nervous system, CNP may function as a key hormone regulating water content and electrolytes homeostasis in the central nervous system. Furthermore, CNP could be one candidate for medical treatment of high intracranial pressure.