Prophylactic maternal N-acetylcysteine in rats prevents maternal inflammation-induced offspring cerebral injury shown on magnetic resonance imaging

OBJECTIVE: Maternal infection or inflammation may induce fetal inflammatory responses associated with fetal injury and cerebral palsy. We sought to assess the inflammation-associated neuroprotective potential of prophylactic N-acetyl-cysteine (NAC). We examined the effect of NAC on prevention of maternal lipopolysaccharide (LPS)-induced neonatal brain injury using magnetic resonance imaging. STUDY DESIGN: Pregnant Sprague Dawley dams (n = 5-8) at embryonic day 18 received intraperitoneal injection of LPS or saline at time 0. Animals were randomized to receive 2 intravenous injections of NAC or saline (time -30 and 120 minutes). Pups were delivered spontaneously and allowed to mature until postnatal day 25. Female offspring were examined by magnetic resonance brain imaging and analyzed using voxel-based analysis after spatial normalization. T2 relaxation time was used to assess white matter injury and diffusion tensor imaging for apparent diffusion coefficient (ADC) to assess white and gray matter injury. RESULTS: Offspring of LPS-treated dams exhibited significantly increased T2 levels and increased ADC levels in white and gray matter (eg, hypothalamus, motor cortex, corpus callosum, thalamus, hippocampus), consistent with diffuse cerebral injury. In contrast, offspring of NAC-treated LPS dams demonstrated similar T2 and ADC levels as control in both white and gray matter. CONCLUSION: Maternal NAC treatment significantly reduced evidence of neonatal brain injury associated with maternal LPS. These studies suggest that maternal NAC therapy may be effective in human deliveries associated with maternal/fetal inflammation.