Can a nerve injury trigger ALS?

A growing collection of anecdotal stories raises the possibility that a nerve injury in one arm or leg may trigger the development of amyotrophic lateral sclerosis, or ALS, a progressive neurodegenerative disease also known as Parkinson's disease. Lou Gehrig, named after the famous New York. Yankee who died in 1941.

The relationship between ALS and athletes is deeper than a baseball player; People who engage in intense physical activity, such as professional athletes and the military, are more likely to be affected by ALS. In some cases, the disease appears to manifest itself after an injury – the muscle weakness at the site of the injury slowly spreads to new areas until the weakness of the muscles responsible for breathing causes suffocation.

Researchers from the University of Illinois at Chicago are the first to demonstrate that a peripheral nerve injury can trigger the onset and spread of the disease in an animal model of ALS. Their findings, published in the journal Neurobiology of the disease, show that rats genetically engineered to develop symptoms similar to ALS have an abnormal inflammatory response in the region of the spinal cord badociated with an injured peripheral neuron. When inflammation of the spinal cord and other damaging processes spread, they cause progressive muscle weakness throughout the body.

"We know that in some patients with ALS, weakness starts at the level of a hand or leg and that the disease spreads.For coincidence, the patient will describe a recent or distant injury of the same hand or the same leg corresponding instead of the onset of the disease.We wanted to investigate how environmental contributions, such as focal nerve damage, affect the onset and spread of ALS, "said Dr. Jeffery Loeb, John S. Garvin Chair in Neurology and Rehabilitation, UIC College of Medicine, and Corresponding Author of the Paper.

"Our results show that a single nerve injury, which is small enough to cause only temporary weakness in normal animals, can trigger a cascade of inflammations in the spinal cord that initiate and provoke the spread of the disease in genetically susceptible animals, "said Loeb. "The ability to precipitate illness through injury gives us a new animal model that we can use to identify ALS treatments that are intended to stop the spread of the disease after it appears. has no treatment that significantly slows or halts the progression of the disease and we are currently focusing all our efforts on developing a drug to do so. "

While an increasing number of genes have been badociated with the development of ALS, only about 10% of ALS patients have one or more of these mutations in the gene and none can explain why the disease has localized weakness. or its mode of propagation. Ninety percent of ALS patients develop the disease for unknown reasons.

"This raises an important question about the relative contributions of the environment to genes or to nature versus education," Loeb said.

One of the most studied genetic mutations in ALS is a gene called SOD1. In their study, Loeb and colleagues used rats with mutated forms of the SOD1 gene, which causes animals to reach higher levels of the SOD1 enzyme and develop ALS-like symptoms, including weakness. Progressive muscle, starting at 15 weeks.

The researchers surgically injured a single nerve in the leg of SOD1 rats and wild rats at the age of 10 weeks. While all rats had reduced strength in the injured leg after the operation, wild-type rats recovered almost completely within a few weeks. SOD1 rats never returned to normal and also had weakness in their leg.

They also found that surgery-injured rats had high and prolonged inflammation, as well as a higher number of microglial cells and astrocytes in areas of the spinal cord badociated with the injured neuron, as well as Inflammation and the presence of these other cells propagating in adjacent neurons.

"This spread of inflammation could potentially explain how the disease spreads once it started at the site of the injury," Loeb said. "Microglia has several roles, but one of the roles is to prune or eliminate the synapses that connect one nerve cell to another." These connections are essential for the normal functioning and survival of patients. neurons during development.Where inflammation and microglia were increased in the spinal cord, we witnessed a reduction up to twice the number of synapses. "

Loeb explained that once a nerve loses its connections with its neighbors, neighboring cells tend to die.

"This chain reaction of cell death could be the cause of the progressive spread of muscle weakness that we observe in ALS," said Loeb.

Provided by
University of Illinois at Chicago