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Role of lysophosphatidic acid in the pathophysiology of spinal cord injury (ROLPASCI)
Date du début: 15 sept. 2010, Date de fin: 14 sept. 2014 PROJET  TERMINÉ 

"Traumatic spinal cord injury (SCI) causes permanent functional deficits due to damage to neurons and supporting cells. The primary mechanical injury triggers inflammatory changes that develops within hours and continues for several days after the injury, which then results in further exacerbation of tissue loss and functional impairments. Reducing the inflammatory response after SCI can therefore be expected to reduce secondary tissue damage and limit functional deficits. A number of mechanisms underlie the recruitment of leukocytes from the peripheral circulation, and the activation of these cells and endogenous microglia and astrocytes within the injured spinal cord. However, the molecules that trigger these responses are not completely known. Lysophosphatidic acid (LPA) is a potent, biologically active lipid mediator that has many physiological functions such as cellular Ca2+ homeostasis and regulation of cytoskeleton, proliferation and survival, adhesion and migration. Recent observations suggest that LPA might be also involved in inflammation. We have preliminary data suggesting that LPA causes a rapid and potent activation of the inflammatory response in the spinal cord, which leads to demyelination and functional impairment. LPA may mediate its effects by signaling via 4 G-protein coupled receptors (LPA1-4). Selectively blocking the receptors involved in detrimental pro-inflammatory responses without affecting those that either are not involved in the pathophysiology of the SCI or might be exerting tissue protection may lead to new interventions to promote repair after SCI, for which there is currently no effective therapy."

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