title: Manganese-enhanced magnetic resonance imaging of hypoxic-ischemic brain injury in the neonatal rat.
abstract: Hypoxic-ischemic injury (HI) to the neonatal brain results in delayed neuronal death with accompanying inflammation for days after the initial insult. The aim of this study was to depict delayed neuronal death after HI using Manganese-enhanced MRI (MEMRI) and to evaluate the specificity of MEMRI in detection of cells related to injury by comparison with histology and immunohistochemistry. 7-day-old Wistar rat pups were subjected to HI (occlusion of right carotid artery and 8% O(2) for 75 min). 16 HI (HI+Mn) and 6 sham operated (Sham+Mn) pups were injected with MnCl(2) (100 mM, 40 mg/kg) and 10 HI-pups (HI+Vehicle) received NaCl i.p. 6 h after HI. 3D T(1)-weighted images (FLASH) and 2D T(2)-maps (MSME) were acquired at 7 T 1, 3 and 7 days after 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 injured hemisphere on day 1 or 3 when immunohistochemistry showed massive ongoing neuronal death. 7 days after HI, increased ME was seen on T(1)-w images in parts of the injured cortex, hippocampus and thalamus among HI+Mn pups, but not among HI+Vehicle or Sham+Mn pups. Comparison with immunohistochemistry showed delayed neuronal death and inflammation in these areas with late ME. Areas with increased ME corresponded 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 neuronal death rather than depicting neuronal death per se.
authors.affiliation: Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway. marius.wideroe@ntnu.no
authors.forename: Marius
authors.initials: M
authors.lastname: Widerøe
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Olsen
authors.forename: Tina Bugge
authors.initials: TB
authors.lastname: Pedersen
authors.forename: Pål Erik
authors.initials: PE
authors.lastname: Goa
authors.forename: Annemieke
authors.initials: A
authors.lastname: Kavelaars
authors.forename: Cobi
authors.initials: C
authors.lastname: Heijnen
authors.forename: Jon
authors.initials: J
authors.lastname: Skranes
authors.forename: Ann-Mari
authors.initials: AM
authors.lastname: Brubakk
authors.forename: Christian
authors.initials: C
authors.lastname: Brekken
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002712:Chlorides; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology*; D007089:Image Enhancement / Q000379:methods*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D017895:Manganese Compounds; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002712:Chlorides; D017895:Manganese Compounds; C025340:manganese chloride