Nadine Kabbani & Robert Lipski, George Mason University, Inova Health System, Annandale, USA

Role of Alpha 7 nicotinic acetylcholine receptor in recovery after spinal cord injury

Funded in: 2013, 2014, 2015


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Problem: After SCI the inflammatory response contributes to the secondary tissue damage

Target: Alpha 7 nicotinic acetylcholine receptor,  which plays a central role in inflammatory response regulation

Goal: Development of an anti-inflammatory  treatment based on genetic predictors to promote functional protection

 

Spinal cord injury results in a severe damage of spinal tissue followed by the loss of functions. The injury affects the neural cells, axons and all other tissue structures. This sets on the activation of immune cells and a cascade of tissue reactions, a process referred to as "secondary damage”.  During this process the size of the lesion and tissue damage increases progressively. Inflammation is considered to be an important contributor to secondary damage after spinal cord injury (SCI).

A complex system of activated immune cells and cytokines contributes to the inflammatory response.  Specific receptors are the targets of the cytokines in the cells. The alpha 7 nicotinic acetylcholine receptor, α7nAChR, plays a central role in regulating the inflammatory response. Previous studies showed that pharmacological inhibitors of α7nAChR have a pro-inflammatory effect while activators of the α7nAChR maintain anti-inflammatory properties.

Beside the role in inflammation there is evidence that neuronal nicotinic acetylcholine receptors (nAChRs) may modulate other neuronal activities within the central nervous system (CNS) and may have a distinct role in regulating neuronal growth and differentiation in developing CNS.

Based on this existing evidence this project will

  • Study if α7nAChRs contribute to recovery from SCI via their anti-inflammatory and neuronal regenerative properties and whether activation of α7nAChRs can serve to promote recovery from SCI.

The expression of this receptor in humans is regulated by a genetic polymorphism, thus the project will

  • Examine in a parallel clinical study the genetic variation in humans regarding the responsible genes. Additionally it will determine how this genetic variation can influence clinical outcome in SCI patients.

 
The results of this project will enable development of anti-inflammatory approaches for treating SCI based on genetic predictors.