Microhemorrhage in a Rat Model of Neonatal Shaking Brain Injury: Correlation between MRI and Iron Histochemistry

Previous studies have shown that neonatal shaking brain injury (SBI) causes transient microhemorrhages (MHs) in the gray matter of the cerebral cortex and hippocampus. Iron deposits and iron-uptake cells are observed surrounding MHs in this SBI model, suggesting local hypoxic-ischemic conditions. However, whether the shaken pups suffered systemic hypoxic-ischemic conditions has remained uncertain. Further, histopathological correlations of MHs on magnetic resonance imaging (MRI) are still unclear. The present study examined MHs after neonatal SBI using a combination of histochemical and susceptibility-weighted imaging (SWI) analyses. Systemic oxygen saturation analyses indicated no significant difference between shaken and non-shaken pups. MHs on postnatal day 4 (P4) pups showed decreased signal intensity on SWI. Iron histochemistry revealed that these hypointense areas almost completely comprised red blood cells (RBCs). MHs that appeared on P4 gradually disappeared by P7–12 on SWI. These resolved areas contained small numbers of RBCs, numerous iron-positive cells, and punctate regions with iron reaction products. Perivascular iron products were evident after P12. These changes progressed faster in the hippocampus than in cortical areas. These changes in MHs following neonatal SBI may provide new insights into microvascular pathologies and impacts on brain functions as adults.