PROGRESSIVE CHANGES IN CORTICAL METABOLITES AT 3 STAGES OF INFANTILE HYDROCEPHALUS STUDIED BY IN-VITRO NMR-SPECTROSCOPY

Infantile hydrocephalus is most often caused by an obstruction in the cerebrospinal fluid flow pathway and results in ventricular dilatation and chronic trauma to the surrounding brain. Surgical treatment allev iates the condition but does not cure or prevent neurological deficits . The H-Tx rat has severe hydrocephalus due to a spontaneous aqueduct obstruction in late gestation. In order to determine how hydrocephalus affects brain metabolism in tissue adjacent to the expanded ventricle s, cortical extracts have been made from groups of hydrocephalic and c ontrol littermates with early, intermediate, and advanced hydrocephalu s at 4, 11, and 21 days after birth. Extracts were analyzed with H-1 a nd P-31 NMR spectroscopy and metabolite peaks were quantified using an external standard. Metabolite concentrations were calculated relative to tissue wet weight and subsequently expressed relative to tissue dr y weight, using values for water content obtained from additional grou ps of rats. In early hydrocephalus there was a significant decrease in the phosphomonoester phosphorylcholine, and there were small, nonsign ificant changes in other compounds. By 11 days, in addition to phospho monoesters, there were significant decreases in ATP, phosphocreatine, and in inorganic phosphate, but with no change in lactate. By 21 days there were also substantial decreases in cholines, inositol, creatine, glutamate, glutamine, aspartate, N-acetylaspartate, alanine, and taur ine. It is concluded that the sequence of pathological events starts w ith changes in membrane lipids. This is followed by reductions in ener gy metabolite which leads to cell swelling with loss of intracellular osmolytes and neurotransmitters. These changes are discussed in relati on to hydrocephalus pathophysiology and to prevention and reversibilit y with shunt treatment.