Defining the influence of lesion level on inflammation and wound healing
Funded in: 2022, 2023, 2024
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Problem: Wound healing response differs based on lesion level
Target: Mapping cells in the injured spinal cord
Goal: New strategies to optimally facilitate spinal cord repair
In Australia, 56% of spinal cord injuries (SCIs) are high-level lesions at or above thoracic level T2. Similar numbers are seen globally, meaning that at least half of all patients are affected by the most severe SCI symptoms. Higher-level SCIs can disrupt nervous signalling to lymphoid organs such as the bone marrow and spleen, impairing normal immune function (known as SCI-induced immune depression syndrome, or SCI-IDS). While links between SCI-IDS and infections have been studied, less is known about how any such impaired immunity affects inflammation and wound healing in the injured spinal cord itself.
The scientists have recently discovered that higher-level lesions show increased scarring - a process linked to dysregulated inflammation. How the spinal cord wound healing response differs based on lesion level is currently not well understood. The researchers will investigate this question as part of this project, in order to advance our understanding of why the injured spinal cord fails to regenerate, and also how new therapeutics may act or apply to patients with different levels of injury.
To achieve this, they will build the first molecular “Google Maps” of experimental SCI, mapping cells in the injured spinal cord across time, space (location within the injured spinal cord) and different lesion levels. Immune and other native spinal cord cell types will be counted, profiled, and their behaviour and interactions predicted across time and space. High- and low-level lesions will be compared to reveal the cellular and molecular determinants of level-dependent changes in the wound healing response. By linking the influence of lesion level to lesion site development and outcomes, it is envisaged that this project will lead to the discovery and design of new strategies that are tailored the needs of individual patients to optimally facilitate spinal cord repair.