Antje Kroner-Milsch, Medical College Wisconsin, Milwaukee, USA

The functional role and therapeutic potential of heme binding proteins

Funded in: 2020, 2021, 2022


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Problem: Blood in the tissue can lead to tissue destruction due to its toxicity
Target: Role and efficacy of capture proteins α1-antitrypsin and α1-microglobulin
Goal: Reducing secondary tissue damage after cervical spinal cord injury

Cervical spinal cord injury (SCI) accounts for approximately 60% of SCIs and can impair motor and sensory function of upper and lower limbs, respiration as well as the function of the autonomic nervous system. SCI associated tissue damage occurs in two major phases: the primary damage is caused by mechanical trauma, followed by secondary damage, which is mediated by a range of factors including inflammation and hemorrhage. Targeting secondary damage in the acute and subacute phase can potentially improve outcomes and reduce functional deficits after SCI.  
Blood in the tissue can lead to tissue destruction due to the toxicity of the blood breakdown products, which also cause additional inflammation. In blood vessels, these breakdown products are neutralized by heme binding proteins. Some of these capture proteins are also present in the central nervous system, where they can help protect the tissue, but their concentration is low and insufficient in the context of SCI.
In this proposal, the role of the capture proteins α1-antitrypsin and α1-microglobulin after SCI will be investigated and their efficacy in reducing secondary tissue damage after cervical spinal cord injury and improve functional recovery.
A mouse model of cervical SCI will be used and behavioral testing and tissue analysis to answer these questions will be applied.
Completion of this project will lead to a better understanding of the hemorrhage induced tissue damage and inflammation after SCI and might lead to a treatment approach to reduce secondary damage and improve functional outcomes after SCI.