Longitudinal manganese-enhanced magnetic resonance imaging of delayed brain damage after hypoxic-ischemic injury in the neonatal rat.

BACKGROUND: Hypoxia-ischemia (HI) in the neonatal brain results in a prolonged injury process. Longitudinal studies using noninvasive methods can help elucidate the mechanisms behind this process. We have recently demonstrated that manganese-enhanced magnetic resonance imaging (MRI) can depict areas with activated microglia and astrogliosis 7 days after hypoxic-ischemic brain injury.

OBJECTIVE: The current study aimed to follow brain injury after HI in rats longitudinally and compare manganese enhancement of brain areas to the development of injury and presence of reactive astrocytes and microglia.

METHODS: The Vannucci model for hypoxic-ischemic injury in the neonatal rat was used. Pups were injected with either MnCl(2) or saline after 6 h and again on day 41 after HI. Longitudinal MRI (T(1) weighted) was performed 1, 3, 7 and 42 days after HI. The brains were prepared for immunohistochemistry after the final MRI.

RESULTS: There was severe loss of cerebral tissue from day 7 to day 42 after HI. Most manganese-enhanced areas in the hippocampus, thalamus and basal ganglia at day 7 were liquefied after 42 days. Manganese-enhancement on day 42 corresponded to areas of activated microglia and reactive astrocytes in the remaining cortex, hippocampus and amygdala. However, the main area of enhancement was in the remaining thalamus in a calcified area surrounded by activated microglia and reactive astrocytes.

CONCLUSION: Manganese-enhanced MRI can be a useful tool for in vivo identification of cerebral tissue undergoing delayed cell death and liquefaction after HI. Manganese enhancement at a late stage seems to be related to the accumulation of manganese in calcifications and gliotic tissue.