Unique properties associated with the brain penetrant iron chelator HBED reveal remarkable beneficial effects after brain trauma

Abstract Iron is postulated to contribute to secondary injury after brain trauma through various pathways including oxidative stress and inflammation. Therefore, one goal is to limit iron toxicity by either directly limiting iron activity, or limiting the secondary cascade mediated by iron, therefore rescuing the brain from damage after trauma. The N,N'-Di(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid monohydrochloride (HBED) is a unique iron chelator that has the ability to cross the intact blood–brain barrier; it has a higher affinity to iron, and it has a longer half-life than most commonly used chelators. A controlled-cortical impact model of traumatic brain injury (TBI) was induced in mice. Mice were subcutaneously injected with HBED immediately after TBI, then at 12 h after, followed by a twice-a-day regimen until an end-point of 3 days. Neurobehavioral tests were performed daily. Cortical injury volume, hemispheric enlargement, and hippocampal swelling were quantified. Perls' iron immunostaini...