Molecular Biological Research related to Developmental Mechanism and New Medical Treatment of Congenital Hydrocephalus

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(1) We have demonstrated in the congenital hydrocehalic HTX-rats that the progression of hydrocephalus impaired the forebrain cholinergic system, whose integrity is essential for learning and memory functions. This result using neurochemical methods has supported our previous findings, that delayd treatment of congenital hydrocephalus was related to the impairment of learning ability in the congenital hydrocephalic HTX rats.Furthermore it was interesting that nerve growth factor (NGF) and some cytokins which play important roles in survival and differentiation of the neuron were increased in the cortex of congenital hydrocephalic HTX rats.The NGF and some cytokins increase in the cortex was supposed to depend on the secretion of reactive astrocytes prominently appearing in the affected cortex and on the accumulation due to impaired retrograde axonal transport of NGF.(2) Intraventricular injection of C-type natriuretic peptide (CNP) in hydroceohalic HTX rats was found to be effective in lowering intracranial pressure and CSF outflow resistance. The results of the present investigation would appear to suggest that CNP could be another candidate for medical treatment of congenital hydrocephalus. The problem regarding the intrinsic regulation of CNP,and the mechanism for lowering intracranial pressure and CSF outflow resistance, remain for further study and investigation.(3) The point mutation of adhesion molecule L1 gene has been demonstrated in human X-linked hydrocephalus, but we could not identify this point mutation in hydrocephalic HTX-rats. Our investigations have shown that there was less gene expression of functional C-type natriuretic peptide receptor in the brain of hydrocephalic HTX-rats than in Wister rats. This result would suggest that the transcription factor, which regulates the C-type natriuretic peptide receptor gene, may be genetically abnormal, but we need further study and investigation.