Old wounds

Millions of people in the world live with chronic spinal cord injuries, and their number increases annually by 250,000-500,000 new cases, the main causes of which are car accidents and falls from heights. The most severe injuries lead to complete paralysis and more than half of them disrupt a person's ability to breathe. Researchers at Case Western Reserve University, working under the guidance of Professor Jerry Silver, have demonstrated in experiments on animal models of chronic injury that the long-term detrimental effect of spinal cord injury on breathing and limb mobility can be reversible.

The approach developed by the authors stimulates the innate ability of the body to very slowly form new processes – axons – in a subpopulation of nerve cells that persist below the damage zone. The activity of these new processes is completely suppressed by a family of potentially inhibitory molecules – proteoglycans. The strategy proposed by the researchers consists in a single injection of the enzyme chondroitinase, which cleaves proteoglycans. The enzyme was injected not into the injury zone itself, but into a fragment of the spinal cord located below.

The experiments used rats whose spinal cord was half cut at the level of the second cervical vertebra, which led to complete unilateral paralysis of the diaphragm. The introduction of the enzyme immediately after the injury minimally stimulated the growth of neurons with a slight restoration of functions. However, during treatment many months after the injury, the therapeutic effect of the enzyme was much more pronounced. Within a week after the drug was administered to animals in the chronic phase of damage, new processes of neurons began to restore the lost function of the diaphragm. After treatment, 70% of rats recovered the ability to use their forelegs to move and study the environment (compared with 30% of animals in the control group).

According to Professor Silver, unexpectedly for the researchers it turned out that the longer the animal was paralyzed, the better the regenerating effect of the enzyme was manifested. The introduction of the enzyme made it possible to restore the activity of the diaphragm 1.5 years after the damage, which is completely unprecedented. A week after therapy, 60% of these animals improved the functioning of the diaphragm, and after 2 weeks positive changes appeared in all rats, even though they suffered from paralysis for almost their entire life.

It is also interesting that short–term exposure to low oxygen levels - respiratory therapy, known as acute intermittent hypoxia, contributed to the strengthening of growing nerve processes. However, the combination of enzymatic therapy with an excessive amount of respiratory therapy led to the development of chaotic activity of a previously paralyzed diaphragm. The authors suggested that the possible development of high abnormal activity may be the reason why the body releases inhibitory molecules that prevent the functional regeneration of axons in the spinal cord. They are currently working on optimizing combination therapy to ensure maximum recovery, especially mobility of the forelimbs.

Article by Warren et al. Rapid and robust restoration of breathing long after spinal cord injury is published in the journal Nature Communications.

Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on Case Western: Case Western Reserve Researchers Restore Breathing and Partial Forelimb Function in Rats with Chronic Spinal Cord Injuries.