Spinal cord injury research

Spinal cord injury research seeks new ways to cure or treat spinal cord injury in order to lessen the debilitating effects of the injury in the short or long term. There is no cure for SCI, and current treatments are mostly focused on spinal cord injury rehabilitation and management of the secondary effects of the condition. Two major areas of research include neuroprotection, ways to prevent damage to cells caused by biological processes that take place in the body after the insult, and neuroregeneration, regrowing or replacing damaged neural circuits. Spinal cord injury research seeks new ways to cure or treat spinal cord injury in order to lessen the debilitating effects of the injury in the short or long term. There is no cure for SCI, and current treatments are mostly focused on spinal cord injury rehabilitation and management of the secondary effects of the condition. Two major areas of research include neuroprotection, ways to prevent damage to cells caused by biological processes that take place in the body after the insult, and neuroregeneration, regrowing or replacing damaged neural circuits. Secondary injury takes place minutes to weeks after the initial insult and includes a number of cascading processes that further harm tissues already damaged by the primary injury. It results in formation of a glial scar, which impedes axonal growth. Animals used as SCI model organisms in research include mice, rats, cats, dogs, pigs, and non-human primates; the latter are close to humans but raise ethical concerns about primate experimentation. Special devices exist to deliver blows of specific, monitored force to the spinal cord of an experimental animal. Epidural cooling saddles, surgically placed over acutely traumatized spinal cord tissue, have been used to evaluate potentially beneficial effects of localized hypothermia, with and without concomitant glucocorticoids. Surgery is currently used to provide stability to the injured spinal column or to relieve pressure from the spinal cord. How soon after injury to perform decompressive surgery is a controversial topic, and it has been difficult to prove that earlier surgery provides better outcomes in human trials. Some argue that early surgery might further deprive an already injured spinal cord of oxygen, but most studies show no difference in outcomes between early (within three days) and late surgery (after five days), and some show a benefit to earlier surgery. Neuroprotection aims to prevent the harm that occurs from secondary injury. One example is to target the protein calpain which appears to be involved in apoptosis; inhibiting the protein has produced improved outcomes in animal trials. Iron from blood damages the spinal cord through oxidative stress, so one option is to use a chelation agent to bind the iron; animals treated this way have shown improved outcomes. Free radical damage by reactive oxygen species (ROS) is another therapeutic target that has shown improvement when targeted in animals. One antibiotic, minocycline, is under investigation in human trials for its ability to reduce free radical damage, excitotoxicity, disruption of mitochondrial function, and apoptosis. Riluzole, an anticonvulsant, is also being investigated in clinical trials for its ability to block sodium channels in neurons, which could prevent damage by excitotoxicity. Other potentially neuroprotective agents under investigation in clinical trials include cethrin, erythropoietin, and dalfampridine. One experimental treatment, therapeutic hypothermia, is used in treatment but there is no evidence that it improves outcomes. Some experimental treatments, including systemic hypothermia, have been performed in isolated cases in order to draw attention to the need for further preclinical and clinical studies to help clarify the role of hypothermia in acute spinal cord injury. Despite limited funding, a number of experimental treatments such as local spine cooling and oscillating field stimulation have reached controlled human trials. Inflammation and glial scar are considered important inhibitory factors to neuroregeneration after SCI. However, aside from methylprednisolone, none of these developments have reached even limited use in the clinical care of human spinal cord injury in the US. Methylprednisolone can be given shortly after the injury but evidence for harmful side effects outweighs that for a benefit. Research is being done into more efficient delivery mechanisms for methylprednisolone that would reduce its harmful effects. Neuroregeneration aims to reconnect the broken circuits in the spinal cord to allow function to return. One way is to regrow axons, which occurs spontaneously in the peripheral nervous system. However, myelin in the central nervous system contains molecules that impede axonal growth; thus, these factors are a target for therapies to create an environment conducive to growth. One such molecule is Nogo-A, a protein associated with myelin. When this protein is targeted with inhibitory antibodies in animal models, axons grow better and functional recovery is improved.