METABOLITE CHANGES IN THE CEREBRAL-CORTEX OF TREATED AND UNTREATED INFANT HYDROCEPHALIC RATS STUDIED USING IN-VITRO P-31-NMR SPECTROSCOPY

The effect of hydrocephalus on cerebral energy metabolites and on inte rmediates of membrane phospholipid metabolism has been studied in H-Tx rats with inherited infantile hydrocephalus. Hydrocephalic rats and r ats with shunts placed at 4-5 days or at 10 days after birth were subj ected to magnetic resonance imaging in vivo before 2-1 days of age to determine the dimensions of the ventricles and cortex. At 21 days, the brains from the three groups of rats, together with age-matched contr ol littermates, were frozen in situ, and chloroform/methanol extracts of cerebral cortex were prepared for high-resolution P-31-NMR spectros copy. Hydrocephalus resulted in modest decreases in most metabolites q uantified. Levels of phosphocreatine, ATP, and diphosphodiesters plus NAD were significantly reduced by 23-32%, and inorganic phosphate cont ent was reduced but not significantly. Levels of the membrane phosphol ipid intermediates phosphorylethanolamine, glycerophosphorylethanolami ne, and glycerophosphorylcholine were also significantly reduced by 30 -33%, indicating changes in membrane metabolism. These general decreas es are consistent with a loss of cell contents, possibly due to change s in dendrite structure in hydrocephalus. Rats shunt-treated at 4-5 da ys were similar to control rats for all energy metabolites, but those treated later at 10 days had reduced phosphocreatine and ATP levels. S hunt-treated rats also had reductions in levels of membrane phospholip ids, some of which occurred in sham-operated rats. It is concluded tha t hydrocephalus leads to reductions in levels of energy metabolites an d in levels of membrane phospholipids and that the changes in energy m etabolites can be reversed by early, but not by later, shunt treatment .