Ng. Harris et al., METABOLITE CHANGES IN THE CEREBRAL-CORTEX OF TREATED AND UNTREATED INFANT HYDROCEPHALIC RATS STUDIED USING IN-VITRO P-31-NMR SPECTROSCOPY, Journal of neurochemistry, 67(5), 1996, pp. 2030-2038
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
.