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Official websites use. Share sensitive information only on official, secure websites. ICH was modeled by intrastriatal injection of collagenase or autologous whole blood. Mice in the post-treatment group were examined for brain lesion volume and edema on day 3 and for neurologic deficits on days 1, 3, and 28 after ICH. Post-treatment reduced brain lesion volume and edema and improved neurologic function. Intracerebral hemorrhage ICH is a common and often fatal stroke subtype. In the aftermath of ICH, iron, a heme degradation product, contributes significantly to the consequent brain injury Wang, After erythrocyte lysis, iron concentrations in the brain can become high enough to stimulate free radical formation, which, in turn, leads to neuronal death and secondary brain injury Wagner et al.
When tested in preclinical studies, the iron chelator deferoxamine has inconsistently shown protection against hemorrhagic brain injury in rats Okauchi et al. Deferoxamine was administered post-ICH in both studies, but in one it was delivered intramuscularly Okauchi et al. Warkentin et al. In our previous study, we confirmed that iron toxicity contributes to collagenase-induced hemorrhagic brain injury in mice and that reducing iron accumulation by post-treatment with deferoxamine i.
The lipid solubility of DP is evidenced by its ability to freely enter brain cells and chelate intracellular free iron, thereby reducing iron-induced cell death Breuer et al. However, the efficacy of DP has not been tested in ICH models, and its effect on iron deposition, iron-mediated oxidative damage, neuroinflammation, and grey and white matter injury after ICH has not been examined.
The objective of this study was, therefore, to investigate the efficacy of DP treatment on ICH outcomes and its effect on iron deposition, iron-mediated oxidative damage, neuroinflammation, and grey and white matter injury. Because the aged population is at greater risk for ICH than are young adults, we used month-old mice to enhance the clinical relevance of the study. This study was conducted in accordance with the National Institutes of Health guidelines for the use of experimental animals.
As described previously Grossetete and Rosenberg, ; Wang et al. Louis, MO at the following stereotactic coordinates: 0. Blood removed from the tail was infused into the left striatum in two time blocks, with a 7-min pause between infusions, according to our published protocol Wang et al.