N-Acetylcysteine rapidly replenishes central nervous system glutathione measured via magnetic resonance spectroscopy in human neonates with hypoxic-ischemic encephalopathy.

Persistent oxidative stress depletes reduced glutathione (GSH), an intracellular antioxidant and an important determinant of CNS injury after hypoxia ischemia. We used standard, short echo time Stimulated Echo Acquisition Mode (STEAM) to detect GSH by magnetic resonance spectroscopy (MRS) in 24 term neonates with hypoxic-ischemic encephalopathy (HIE), on day of life 5-6, after rewarming from therapeutic hypothermia. MRS demonstrated reliable, consistent GSH of 1·64 ± 0·20 mM in the basal ganglia immediately before intravenous infusion of N-acetylcysteine. N-acetylcysteine resulted in a rapid and significant GSH increase to 1·93 ± 0.23 mM within 12-30 min after completion of infusion ( n = 21, p < 0.0001, paired t-test), compared with those who did not receive N-acetylcysteine ( n = 3, GSH = 1.66 ± 0.06 mM and 1.64 ± 0.09 mM). In one perinatal stroke patient, GSH in the diffusion-restricted stroke area was 1.0 mM, indicating significant compromise of intracellular redox potential, which also improved after N-acetylcysteine. For comparison, GSH in healthy term neonates has been reported at 2.5 ± 0.9 mM in the thalamus. This is the first report to show persistent oxidative stress reflected in GSH during the subacute phase in neonates with HIE and rapid response to N-acetylcysteine, using a short echo MRS sequence that is available on all clinical scanners without spectral editing.