Spinal cord injury research looks for new ways to cure or treat spinal cord injury to reduce the effects of debilitating injury in the short or long term. There is no cure for SCI, and current treatment is mostly focused on rehabilitation of spinal cord injury and management of secondary effects of the condition. The two main areas of research include nerve shielding, ways to prevent damage to cells caused by biological processes that occur inside the body after humiliation, and neuroregeneration, regrow or replace damaged neural circuits.
Video Spinal cord injury research
Pathophysiology
Secondary injuries occur several minutes to weeks after the initial insult and include a number of further cascade processes that harm the tissues damaged by primary injury. This results in the formation of a glia scar, which inhibits axonal growth.
Maps Spinal cord injury research
Animal model
Animals used as SCI model organisms in the study included mice, rats, cats, dogs, pigs, and non-human primates; the latter close to humans but raises ethical concerns about primate experiments. Special devices exist to deliver a special blow, the strength of which is monitored into the spinal cord of experimental animals.
Saddles epidural coolants, through surgery through acute trauma spinal tissue, have been used to evaluate potentially beneficial effects of local hypothermia, with and without joint glucocorticoids.
Surgery
The current surgery is used to provide stability to the spinal injury or to reduce the pressure of the spinal cord. How quickly after an injury to perform a decompression surgery is a controversial topic, and it is difficult to prove that previous surgery gave better results in human trials. Some argue that early surgery may further relieve spinal cord injuries, but most studies show no difference in outcomes between baseline (within three days) and late surgery (after five days), and some show benefits for prior surgery.
Neuroprotection
Nerve protection aims to prevent damage caused by secondary injury. One example is targeting calpain protein that appears to be involved in apoptosis; inhibiting protein has produced better results in animal testing. Iron from the blood damages the spinal cord through oxidative stress, so one option is to use a chelation agent to bind iron; animals treated in this way have shown better results. Free radical damage by reactive oxygen species (ROS) is another therapeutic target that has shown improvement when targeted in animals. An antibiotic, minocycline, is being investigated in human trials because of its ability to reduce free radical damage, excitotoxicity, impaired mitochondrial function, and apoptosis. Riluzole, anticonvulsants, is also being studied in clinical trials because of its ability to block sodium channels in neurons, which can prevent damage by excitotoxicity. Other potentially neuroprotective agents under investigation in clinical trials include cethrin, erythropoietin, and dalfampridine.
Hypothermia
One experimental treatment, therapeutic hypothermia, is used in medicine but there is no evidence that it improves results. Some experimental treatments, including systemic hypothermia, have been done in isolated cases to draw attention to the need for further clinical and preclinical studies to help clarify the role of hypothermia in acute spinal cord injury. Although funding is limited, a number of experimental treatments such as local spinal cooling and oscillatory field stimulation have reached controlled human trials.
Methylprednisolone
Glial inflammation and scarring are considered important inhibiting factors for neuroregeneration after SCI. However, in addition to methylprednisolone, none of these developments has achieved even limited use in clinical care of human spinal injury in the US. Methylprednisolone may be given immediately after injury but evidence for harmful side effects outweighs its benefits. Research is being conducted into a more efficient delivery mechanism for methylprednisolone that will reduce harmful effects.
Neuroregeneration
Neuroregeneration aims to reconnect damaged circuits in the spinal cord to allow for back function. One is by growing axons, which the peripheral nervous system can do, but myelin in the central nervous system has molecules that inhibit axonal growth; so these factors are the targets for therapy to create an environment conducive to growth. One such molecule is Nogo-A, a protein associated with myelin; in animal models when these proteins are targeted with antibodies to it, the axons grow better and more functional recovery occurs.
Stem cells
Stem cells are cells that can differentiate to become different types of cells. The hope is that stem cells transplanted into the spinal cord injury area will allow neuroregeneration. The types of cells studied for use in SCI include embryonic stem cells, neural stem cells, mesenchymal stem cells, olfactory ensheathing cells, Schwann cells, activated macrophages, and induced pluripotent stem cells. When stem cells are injected in the area of ​​damage in the spinal cord, they secrete neurotrophic factors, and these factors help neurons and blood vessels to grow, thus helping to repair the damage. It is also necessary to create an environment in which stem cells will grow.
The ongoing Phase 2 of 2016 presents data showing that after 90 days of treatment with oligodendrocyte progenitor cells derived from embryonic stem cells, 4 of 4 subjects with complete cervical injury had an increase in motor rates, with 2 of 4 improving two motor levels ( on at least one side, with one patient raising two motor levels on both sides). The original endpoint of the trial was 2/5 patients who improved two levels on one side within 6-12 months. All 8 cervical subjects in this 1-2 phase trial have demonstrated an increase in upper limb motor score (UEMS) relative to baseline with no serious adverse side effects, and phase 1 2010 trials in 5 thoracic patients found no safety problems after 5-6 years of follow-up.
Six-month efficacy data is expected in January 2017; meanwhile, higher doses are being investigated and this study now also recruits patients with incomplete injuries.
Embry stem cells
Embryonic stem cells (ESC) are potentially compounded; They can develop into every type of cell in the fetus.
Nerve root cells
Neural stem cells (NSCs) are multipotent; they can differentiate into different types of nerve cells, either neurons or glia, ie oligodendrocytes and astrocytes. The hope is that these cells when injected into the spinal cord are injured will replace dead neurons and oligodendrocytes and the secreting factors that support growth. However they may fail to differentiate into neurons when transplanted, whether they remain undifferentiated or become glia. Phase I/II clinical trials that inculcate NSC to humans with SCI begin in 2011 and end in June 2015.
Mesenchymal stem
Mesenchymal stem cells do not need to come from the fetus, so avoid the difficulty surrounding ethics; they come from tissue including bone marrow, adipose tissue, umbilical cord. They are considered to be plural potential. Unlike other stem cell types, mesenchymal cells do not present the threat of tumor formation or trigger an immune system response. Animal studies with bone marrow stem cell injections have shown improvement in motor function; But not so in the post-injury year-end human experiment. More experiments are underway. Adipose and stem cell umbilical tissue require further research before human trials can be performed, but two Korean studies began investigating adipose cells in SCI patients.
olfactory insertion cells
A tissue transplant such as olfactoryus olfactory ensheathing cell of olfactory bulbs has been shown to produce beneficial effects on injured spinal cord in mice. Experiments have also begun to show success when olfactory enzyme cells are transplanted into humans with a broken spinal cord. People have restored the sensation, use of previously paralyzed muscles, and bladder and intestinal function after surgery, such as Darek Fidyka.
Induced pluripotent stem cells
Japanese researchers in 2006 found that adding certain transcription factors to the cells caused them to differentiate again. In this way the patient's own tissue can be used, reducing the possibility of rejection of transplantation.
The engineering approach
The latest approach has used a variety of engineering techniques to improve the repair of spinal cord injury. The use of biomaterials is an engineering approach to SCI treatment that can be combined with stem cell transplantation. They can help deliver cells to the wounded area and create an environment that encourages their growth. The general hypothesis behind engineered biomaterials is that bridging lesion sites using growth permissive scaffolds can help axons grow and thus improve function. The biomaterials used should be strong enough to provide sufficient but soft enough support for not suppressing the spinal cord. They must degrade over time to make the body to regenerate tissues. Engineered treatments do not induce an immune response because biological treatments are possible, and they can easily be melodic and reproducible. In-vivo hydrogel administration or self-assembling nanofibers have been shown to promote the growth of axonal and partial functional shoots. In addition, the administration of carbon nanotubes has been shown to increase the motor axon extension and reduce the volume of lesions, without inducing neuropathic pain. In addition, the administration of poly-lactic acid microfiber has shown that guidance of topographic course alone may encourage axonal regeneration to the site of injury. However, all of these approaches lead to simple behavioral or functional recovery that indicates that further investigation is required.
Hydrogels
Hydrogels are structures made of polymers designed to resemble the natural extracellular matrix around the cell. They can be used to help deliver more efficient drugs to the spinal cord and to support cells, and they can be injected into the wound area to fill the lesion. They can be implanted into a lesion site with drugs or growth factors in it to provide the best access chemicals to the damaged area and allow for continued release.
Exoskeletons
The technology to create a powerful exoskeleton, a wearable engine to help the movement walk, is currently making significant progress. There are products available, such as Ekso, which allows individuals with complete C7 (or incomplete) spinal cord injuries to stand upright and make technologically assisted steps. The initial goal for this technology is for functional based rehabilitation, but as technology develops, so does its use.
Functional electrical stimulation (FES) uses a coordinated electrical shock to the muscles to cause them to contract with the walking pattern. While it can strengthen muscles, a significant disadvantage for FES users is that their muscles get tired after a short time and distance. One of the research directions combines FES with an exoskeleton to minimize the disadvantages of both technologies, supporting one's joint and using muscles to reduce the required power of the engine, and thus its weight.
Brain-computer interface
Recent research has shown that combining brain-computer interfaces and functional electrical stimulation can restore the voluntary control of the paralyzed muscles. A study with monkeys suggests that it is possible to directly use commands from the brain, bypassing the spinal cord and allowing limited control and hand function.
Bone marrow implant
Spine implant implants, such as e-dura implants, designed for implantation on the surface of the spinal cord, are being studied for paralysis after spinal cord injury. Human studies have not been done yet.
The E-dura implant is designed using a soft neurotechnology method, in which electrode and microfluid delivery systems are distributed along the spinal implant. Chemical stimulation of the spinal cord is given through the microfluidic channels of the e-dura. The e-dura implants, unlike previous surface implants, are very similar to the physical properties of live tissue and can provide electrical impulses and pharmacological substances simultaneously. Artificial dura mater is built through the utilization of PDMS and hydrogel gelatin. Hydrogels simulate spinal tissue and silicone membranes simulate dura mater. These properties enable e-dura implants to maintain long-term applications to the spinal cord and brain without causing inflammation, scarring, tissue buildup, and rejection usually caused by surface implants that rub against nerve tissue.
References
Bibliography
- Bigelow, S.; Medzon, R. (June 16, 2011). "Spinal Injuries: Nerves". In Legome, E.; Shockley, L.W. Trauma: A Comprehensive Emergency Treatment Approach . Cambridge University Press. ISBN: 978-1-139-50072-2. CS1 maint: Using parameter editor (link)
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