Abstract WP258: Unique Properties Associated With the Iron Chelator HBED Reveal Remarkable Beneficial Effect After Brain Trauma

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Abstract

Introduction: Iron is postulated to contribute to secondary injury after brain trauma through many pathways. Iron participates in the oxidative stress and inflammation processes. The N,N’-Bis(2-hydroxybenzyl)ethylenediamine-N,N’-diacetic acid (HBED) is a unique iron chelator as it has ability to cross the blood brain barrier, higher affinity to iron, and longer half-life than most commonly used chelators.

Hypothesis: Our study is investigating the efficacy of HBED in protecting brain tissue and improving behavioral outcomes after brain trauma. We are also exploring the histological and biochemical mechanisms behind its beneficial effect.

Methods: WT C57BL/6 mice were injected with HBED SQ after TBI and then twice a day till an end point of 3 days. Controlled-cortical impact trauma model was used to inflict injury. Neurobehavioral tests were performed to assess the degree of neurological deficit and short-term recovery over 3 days. We determined cortical Injury volume, hemispheric volume, hippocampal swelling, and corpus callusom volume/thickness. Perls’ and immunohistochemical staining analysis is being performed to assess iron deposits and to inspect microgliosis, oxidative stress injury, and determine the astrocyte roles in regulating brain edema.

Results: Thus far, data revealed that HBED treatment significantly decreases motor deficits and improves short term recovery. It also reduces each of cortical injury volume by 36.5±23.5% (p<0.001), hippocampal swelling by 23.3±13.2% (p<0.05), and total hemispheric volume by 13.2±9.5% (p<0.05). Recent data on upcoming results will also be reported.

Conclusion: This iron chelator HBED protects against acute traumatic motor deficits and promotes short-term recovery. It reduces cortical injury, hippocampal swelling, and total hemispheric volume after traumatic brain injury. These findings indicate that using HBED in humans may have similar robust effect and ultimately facilitates functional recovery.

[This work was supported in part by grants from the McKnight Brain Research Foundation, Brain and Spinal Cord Injury Research Trust Fund, and AHA 33450010, and NIH R21NS095166.]

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