Brain
iron overload is involved in
brain injury after
intracerebral hemorrhage (ICH). There is evidence that systemic administration of
minocycline reduces brain
iron level and improves neurological outcome in experimental models of hemorrhagic and
ischemic stroke. However, there is evidence in
cerebral ischemia that
minocycline is not protective in aged female animals. Since most ICH research has used male models, this study was designed to provide an overall view of ICH-induced
iron deposits at different time points (1 to 28 days) in aged (18-month old) female Fischer 344 rat ICH model and to investigate the
neuroprotective effects of
minocycline in those rats. According to our previous studies, we used the following dosing regimen (20 mg/kg, i.p. at 2 and 12 h after ICH onset followed by 10 mg/kg, i.p., twice a day up to 7 days). T2-, T2⁎-weighted and T2⁎ array MRI was performed at 1, 3, 7 and 28 days to measure brain
iron content, ventricle volume, lesion volume and
brain swelling. Immunohistochemistry was used to examine changes in
iron handling
proteins, neuronal loss and microglial activation. Behavioral testing was used to assess neurological deficits. In aged female rats, ICH induced long-term perihematomal
iron overload with upregulated
iron handling
proteins,
neuroinflammation, brain
atrophy, neuronal loss and neurological deficits.
Minocycline significantly reduced ICH-induced perihematomal
iron overload and
iron handling
proteins. It further reduced
brain swelling,
neuroinflammation, neuronal loss, delayed brain
atrophy and neurological deficits. These effects may be linked to the role of
minocycline as an
iron chelator as well as an inhibitor of
neuroinflammation.