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Project

Role of haptoglobin and hemopexin in secondary damage after SCI

Funder: Craig H Neilsen Foundation

Funding period
USD 300 K
Funding amount
Abstract
The main objective of this study is to investigate and modulate the hemorrhage induced secondary tissue damage after spinal cord injury (SCI), in order to minimize tissue damage and to promote an environment that is permissive for healing and repair. SCI is a life altering condition, and any strategies that facilitate improvement in these conditions can have far-reaching effects on quality of life for affected individuals. We propose to assess the role of haptoglobin and hemopexin after SCI and the effects of treatment with these proteins in reducing secondary damage and promoting functional recovery. The primary tissue damage after SCI occurs from the trauma itself, and secondary damage is caused by subsequent events, including hemorrhage and inflammation. Secondary damage contributes significantly to the pathology and thereby to the severity of the functional deficits. Red blood cells (RBCs) are present at the site of SCI due to trauma-induced hemorrhage and macrophages that phagocytose RBCs acquire a proinflammatory phenotype. In addition, blood breakdown products like free hemoglobin and heme are toxic, reactive and pro-inflammatory. In the vasculature, high concentrations of sequestering proteins like haptoglobin and hemopexin are present to bind these blood breakdown products. In the CNS tissue, only low concentrations of these sequestering proteins are present. However, they play an important role in hemorrhage related conditions of the CNS, where overexpression can lead to a better outcome and reduction or absence of these proteins to a deterioration. Haptoglobin and hemopexin have not been investigated in the context of SCI. We therefore propose to characterize the expression of haptoglobin, hemopexin and their receptors after SCI and identify expressing cell types. We also propose to assess the functional role of haptoglobin and hemopexin after SCI. We will study the functional outcome in hemopexin knockout mice after SCI and the treatment effect of haptoglobin and hemopexin using the contusion injury model (IH Impactor device) with a moderate contusion injury (50 kDyne) in mice. Treatment effects will be assessed functionally (BMS locomotor score), histologically and by using early and late MRI measurement to quantify hemorrhage and tissue damage in correlation with behavioral outcomes. This study will provide insights into the role of haptoglobin and hemopexin after SCI. These experiments could lead to the development of a potential treatment to reduce secondary tissue damage and promote functional recovery after SCI. (CHN: SCIRTS chn:wdg)
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System

Categories
  • FOR (ANZSRC)

    1103 Clinical Sciences

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC

    Neurosciences

  • RCDC

    Spinal Cord Injury

  • RCDC

    Neurodegenerative

  • HRCS HC

    Neurological

  • HRCS RAC

    2.1 Biological and endogenous factors

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science