Hc. Jones et al., PROGRESSIVE CHANGES IN CORTICAL METABOLITES AT 3 STAGES OF INFANTILE HYDROCEPHALUS STUDIED BY IN-VITRO NMR-SPECTROSCOPY, Journal of neurotrauma, 14(9), 1997, pp. 587-602
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.