A team of scientists has discovered that oxidizing species regulate the regeneration of damaged neurons after spinal cord injury. These advances can inspire the creation of new drugs that activate spinal regeneration after an injury regulating the oxidation process that comes with it. The study also suggests reviewing the indiscriminate use of antioxidant therapies after a nerve injury, since the treatment can block the body’s own regenerative response.
Anti-inflammatories and antioxidants are currently the treatment received by people affected by a nerve or spinal cord injury to mitigate the damage. After an injury to a nerve, inflammation occurs and the immune system is activated, which sends the macrophages to clean the damaged area. In addition, high levels of oxidation also occur, causing damage to the membrane and DNA of some neurons and even the death of some cells.
Although at first everything would lead to think that inhibiting the inflammatory and oxidative response after an injury would avoid the secondary damage of that process, researchers from the Institute of Bioengineering of Catalonia (IBEC), in collaboration with Imperial College London have discovered that the oxidative process can contribute to promote the regeneration of axons after a nerve injury.
In a study with mice, IBEC researchers Arnau Hervera, the first author of the study, and José Antonio del Río investigated the mechanism that mediated regeneration after spinal cord injuries. To do this, they first submitted the animals to conditioning nerve lesions, known since the 70s for contributing to regeneration in later lesions, but which mechanisms are not yet clear.
“When there is a first slight injury to the nervous system, recovery after an acute injury is more effective. We could think of a mechanism similar to the one caused by vaccines, that is, as a cellular memory,” says Hervera.
Regeneration after spinal cord injuries
The research group focused on understanding the mechanism behind that first conditional nerve injury. During this process, high levels of oxidation or reactive oxidant species (ROS) are produced.
“We realized that reactive oxidant species always accompanied regeneration after conditional lesions. For that reason, we decided to simulate the lesion by simply releasing these ROSs near the damaged area,” explained the researcher.
To simulate the regenerative effect of the conditional lesion, they administered a type of ROS (oxygenated water) in the sciatic nerve of a group of mice. After a posterior spinal cord injury, and after four weeks, the mice undergoing treatment with ROS showed functional improvements.
“A conditional lesion would never be of therapeutic use, but if we understand the mechanisms behind it and how this oxidation works, we can control and improve regeneration after spinal cord injuries,” says Del Río, principal investigator at IBEC and the Institute of Neurosciences at the University of Barcelona (UB), as well as a member of CIBERNED and a professor at the UB.
In their search for the mechanism responsible for this oxidation via EOR, the scientists identified macrophages (immune cells typically associated with inflammatory processes) as responsible for the necessary signaling by ROS in damaged neurons to promote the regeneration of injured axons.
This discovery, published in the journal Nature Cell Biology, could inspire the creation of new regenerative therapies that promote recovery after nerve or spinal cord injury by regulating ROS signaling.
“The solution would be to modulate the oxidant and inflammatory response of the body instead of blocking it, as it is currently done,” said Arnau Hervera. “Our findings question the efficacy of the indiscriminate use we make today of antioxidant and anti-inflammatory therapies against nerve injuries, as we have many evidences of the need to have an immune response that participates in the regeneration process“, concludes Simone Di Giovanni of the Imperial College and responsible for the investigation.