Spinal cord injuries (SCIs) are very painful and have a high risk for causing paralysis. One of the most severe side effects is the inability to breathe without assistance. Using laboratory models, however, neuroscientists have discovered that two sets of neural signals control diaphragm movement. Through rodent testing, they may have found a drug that can restore diaphragm movement so that humans with SCIs can breathe without ventilation.

The Dangers of Mechanical Ventilation

Falls and vehicle accidents are the most common causes of SCIs, which paralyze about 17,000 people every year. Many of them have to rely on mechanical ventilation to breathe. However, only being able to breathe with a ventilator greatly increases patients' risk for fatal infection.

The reason is because bacteria can build up in the breathing tubes, which have direct contact with the lungs. The bacteria can cause pneumonia or septicemia, which are the main causes of death among SCI patients. In addition, patients on ventilation can experience muscle atrophy in their diaphragms because they aren't using the muscle. This robs them of the chance to breathe on their own again.

To reduce mechanical ventilation reliance, Case Western Reserve University School of Medicine Neurosciences Professor Jerry Silver, PhD, and graduate student Jared Cregg may have developed a way to restore diaphragm function. They started by learning how the body controls breathing.

The Connection Between Spinal Cord Injury and Breathing

Central pattern generators (CPGs) are neural networks in the brain that control rhythms in the central nervous system. The CPG that controls breathing is located in the medulla region, which is in the brain stem at the base of the skull. The signals to breath start in the brain and are transmitted to spinal cord motor neurons. When an SCI severs the connection between the brain and nerves, it cuts off the ability to breathe.

However, the brain isn't the source of all signals in the body that control muscle movement. The signals that make our limbs move, for example, come from the spinal cord. They're sent to motor neurons that are independent of the brain. CPGs send signals that inhibit movement, which make our movements more precise. Professor Silver and his team explains that they wanted to find out if similar signals came from the spinal cord to control diaphragm movement and if they could restore breathing by blocking the signals from the CPG.

Helping Adult Paralyzed Mice Breathe on Their Own

After experimenting on ex vivo spinal cords, the researchers used a grafting technique on adult mice with complete cervical SCI. The technique bridges nerves from the brain to neurons below the injury. The neuroscientists examined how electrical signals could be sent using this network to spur diaphragm movement.

With a combination of drugs, they induced bursts of electricity to show that they originated in the spinal cord rather than the brain. The drugs blocked the inhibitory signals that the CPG produced. The researchers found that the mice could breathe completely independent of the brain when they did that. Their breathing was even consistent with normal patterns.

The Possibility of Restoring Breathing in Humans

The scientists suggest that the neural network may be used to bypass missing signals from the brain to restore motor function below the site of an SCI in humans. However, this biotechnology is far from ready for human use, says Cregg. It needs further development and testing before it can be implemented as a resolution for human injuries.