Magnetic Resonance Imaging of Hypoxic-Ischemic Brain Injury Development in the Newborn Rat

Article history:Received 24 June 2008Revised 2 December 2008Accepted 3 December 2008Available online 24 December 2008Hypoxic–ischemic injury (HI) to the neonatal brain results in delayed neuronal death with accompanyinginflammation for days after the initial insult. The aim of this study was to depict delayed neuronal death afterHI using Manganese-enhanced MRI (MEMRI) and to evaluate the specificity of MEMRI in detection of cellsrelated to injury by comparison with histology and immunohistochemistry. 7-day-old Wistar rat pups weresubjected to HI (occlusion of right carotid artery and 8% O2 for 75 min). 16 HI (HI+Mn) and 6 sham operated(Sham+Mn) pups were injected with MnCl2 (100 mM, 40 mg/kg) and 10 HI-pups (HI+Vehicle) received NaCli.p. 6 h after HI. 3D T1-weighted images (FLASH) and 2D T2-maps (MSME) were acquired at 7 T 1, 3 and 7 daysafter HI. Pups were sacrificed after MR-scanning and brain slices were cut and stained for CD68, GFAP, MAP-2,Caspase-3 and Fluorojade B. No increased manganese-enhancement (ME) was detectable in the injuredhemisphere on day 1 or 3 when immunohistochemistry showed massive ongoing neuronal death. 7 daysafter HI, increased ME was seen on T1-w images in parts of the injured cortex, hippocampus and thalamusamong HI+Mn pups, but not among HI+Vehicle or Sham+Mn pups. Comparison with immunohistochem-istry showed delayed neuronal death and inflammation in these areas with late ME. Areas with increased MEcorresponded best with areas with high concentrations of activated microglia. Thus, late manganese-enhancement seems to be related to accumulation of manganese in activated microglia in areas of neuronaldeath rather than depicting neuronal death per se.© 2008 Elsevier Inc. All rights reserved.