The following key strategies of research towards regeneration/Neuroprotection after spinal cord injury are described below (source: Christopher Reeve Foundation website):
Neuroprotection. For weeks and possibly months after a spinal cord injury, the cellular casualty count continues to rise. The body's immune responses, the chemicals spewed by dying cells, and other natural processes triggered by an injury damage the cells that survived the initial trauma and cause others to self-destruct. The mayhem amplifies the size of the lesion and the loss of function. If this biological ripple effect could be prevented or contained, the injury might wreak less havoc. Read more about apoptosis, the cellular suicide mechanism that a spinal cord injury activates.
Axon Growth and Remyelination. Spinal cord injuries destroy axons, but the neurons to which they belonged often are spared. Unfortunately, these neurons do not simply send out new axons nor repair the damaged ones. Some investigators are trying to "convince" neurons to do just that. One strategy is to reboot the development program in neurons so that they grow new axons that then could recreate the nerve circuits that an injury disrupts. Other researchers are exploring how the peripheral nervous system in the arms and legs repairs nerve damage, hoping that the process could be mimicked in the spinal cord. Another challenge is posed by spinal axons that survive the injury but then shed their protective wrap of myelin, which had enabled them to transmit signals. Researchers are closing in on a therapy that would remyelinate these stripped axons and also might reverse the demyelinating disease multiple sclerosis. A remyelination strategy also would ensure that if neurons could be coaxed to regrow their axons after an injury, they would have a proper myelin sheath. Read more about axonal growth and demyelination.
Growth Inhibition. Unlike cells in the peripheral nervous system, cells in the central nervous system do not repair themselves after an injury. However, researchers now believe that spinal neurons might put out new axons were it not for the body's natural responses to a trauma, including inflammation. Those reactions transform the area around the lesion into hostile territory for axon regeneration. In addition, the myelin sheath, which normally insulates axons and enables them to transmit nerve impulses, also contains proteins that prevent neurons from regenerating their axons after a spinal cord injury. One day treatments will be developed that will stymie growth-inhibiting molecules or prevent them from congregating at the injury site so that the body can repair lost spinal-cord circuitry. Another strategy involves either protecting new axons from the toxic environment or bolstering them so they can muscle through it. Scientists also are beginning to explore mechanisms inside neurons themselves that interfere with axon regrowth and present new targets for therapy.
Axon Guidance, Synapse Formation, and Neurotransmission. Spinal cord researchers have had increasing success persuading neurons to regenerate their damaged axons following a spinal cord injury. However, in order to rebuild nerve circuitry and restore lost function, those newborn axons must travel distances up to several feet, recognize their target neurons, and forge working connections — or synapses — with them. In addition, the full complement of neurotransmitters, the chemicals that improve neuron-to-neuron communication, and their receptors also must be restored. Toward that end, an increasing number of researchers are focusing on how the brain and spinal cord are assembled in developing organisms. They study how certain guidance molecules keep elongating axons on track and how the growing tip of the axon receives information and nourishment during the journey. If this formative process could be restarted in the adult, then doctors would have a valuable tool for repairing the injured spinal cord. To help people recover function, scientists also are testing ways to exploit and strengthen the connections between the brain and spinal cord that survive most injuries.
Cellular Replacement, Therapeutic Cells and Substrates. One approach to spinal cord repair involves the replacement of neurons and their cadre of support cells that are destroyed or damaged by the injury and its aftermath. Toward that end, some scientists are trying to generate dependable lines of stem cells that, when transplanted, would evolve into the cell types needed to fix the injured cord. [See Stem Cells below.] Other researchers are experimenting with different types of transplanted cells and tiny guidance channels, which would provide the scaffolding, or substrate, to support new axons and keep them on track as they grow across a breach in the spinal cord. Both the cells and the tiny devices can be engineered to deliver substances that would promote the regenerative process and protect surviving cells. Peripheral nerve transplants also have shown promise as a way to patch nerve circuits. Another approach involves restarting the mechanisms that first created the nervous system. Read more about spinal cord cells - neurons, astrocytes, microglia, and oligodendrocytes - and the challenges of central nervous system repair following an injury.
Stem Cell Research. Stem cells hold promise for treating a host of diseases and injuries. The most primitive of these cells, embryonic stem cells, give rise to all the different types of tissues in the body. Higher order stem cells known as neuroprogenitor cells spin off the all the cells that become the brain and spinal cord. If researchers can learn how to control the parent cells and the fate of their offspring, then stem cells might one day repair a damaged spinal cord. All types of stem cells are self-renewing in the body and in the laboratory, so large quantities might be grown for medical purposes. Pools of neuroprogenitors also appear to lie dormant in the recesses of the brain and spinal cord that might be roused and dispatched to the site of an injury. Researchers are working on understanding the basic biological mechanisms of stem cells with the hope that they might one day restore function to people with spinal cord injury.
Read about stem cells, the potential of stem cell research, our position on stem cells, and the latest stem cell research.New Tools and Models for Spinal Cord Research. To find effective treatments for spinal cord injuries, researchers must understand the exact course, over both time and distance, of the biological tempest that the injury spawns. Moreover, they must thoroughly test promising treatments in animal models of different types of injuries. The Reeve Foundation encourages the creation and use of new technologies and devices that will aid spinal cord research as well as the development of sophisticated models of spinal cord injuries.
For more detailed information about these key lines of research visit http://www.christopherreeve.org
Latest update of this section in October 2012 by the ESCIF Regenerative Research Working Group. For any comments or questions, pls contact research@escif.org |