Steve Lacroix , CHUL Research Center, Quebec, Canada

Identification of the endogenous signals initiating inflammation and tissue damage in the injured spinal cord

Funded in: 2013, 2014, 2015


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Problem: The Inflammatory response plays a role in the “secondary injury” after SCI

Target: Cells and molecules involved in the initiation of neuroinflammation after SCI, particularly interleukin receptor 1

Goal: To find a neuroprotective therapy for SCI

 

Spinal cord injury leads to the damage of numerous axons and the death of many neurons, which results in severe functional impairment. The acute tissue damage not only affects the neural cells but also extends to all other tissue structures like the blood vessels and sets on a cascade of tissue reactions (neuroinflammation).

This inflammatory response plays a role in the “secondary damage”. A release of molecules called chemokines trigger the recruitment of aggressive blood derived immune cells at sites of injury, causing additional cell death and myelin loss. This secondary damage is responsible for a progressive increase of the tissue damage, lesion size and functional deficits.

While the acute cell death cannot be prevented, strategies aimed at preventing secondary degeneration represent a potentially effective therapy for SCI. It is thus of great relevance to characterize the cellular and molecular events that lead to secondary damage. In previous studies Dr. Lacroix’s team could show that the synthesis and release of chemokines and the infiltration of the aggressive immune cells are modulated by so called interleukins acting through interleukin receptors. These studies demonstrated  that the absence of the interleukin receptor 1 (IL-1R1) or its ligands led to better functional recovery after SCI.

This project aims:

  • To further identify the cells and molecules involved in the initiation of neuroinflammation after SCI and to clarify the exact cellular source of IL-1
  • To further examine the contribution of immune cells to neuronal and myelin damage after SCI and test the efficacy of anti-IL-1 therapies in vivo in a SCI model

The result may result in a neuroprotective therapy after SCI.