Can a nerve injury induce amyotrophic lateral sclerosis?

What is amyotrophic lateral sclerosis?Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. Motor neurons reach the spinal cord from the brain and from the spinal cord to the muscles of the entire body. Progressive degradation of motor neurons in ALS ultimately leads to their death. When a motor neuron dies, the brain's ability to initiate and control muscle movement is lost.

ALS usually begins with muscle twitching and weak limbs or slurred speech. Finally, ALS influences the control of the muscles needed to move, talk, eat and breathe. There is no cure for ALS, and the disease is eventually fatal.

In 1993, scientists discovered that copper/zinc superoxide dismutase, also called SOD1, produced by mutations in the SOD1 gene is associated with approximately 20% of familial ALS. The enzyme SOD1 is a powerful antioxidant that protects the body from free radical damage from mitochondria. Free radicals are highly active molecules produced by cells during normal metabolism. Free radicals can accumulate and cause damage to DNA and proteins in cells. If the oxidative stress defense fails, the cells will go to apoptosis, then leading to progressive paralysis in muscle.

People who engage in intense physical activity, such as professional athletes and military personnel, are more likely to be affected by ALS. In some cases, the disease appears to start after the injury, with muscle weakness in the injured area slowly spreading to new areas until the muscle weakness responsible for breathing causes suffocation.

A growing number of anecdotal accidents have shown that nerve damage in the arms or legs can be an inducement for the development of ALS.

Now, researchers at the University of Illinois at Chicago have first demonstrated that peripheral nerve injury can trigger occurrence and transmission in rats of ALS. Their study reported in the Neurobiology of Disease showed that rats genetically engineered to develop ALS-like symptoms have an abnormal inflammatory response in the spinal cord region associated with damaged peripheral neurons. As inflammation of the spinal cord and other destructive processes spread, they can lead to progressive muscle weakness throughout the body.

In some patients with ALS, the disease spreads when weakness begins in the hands or legs. Coincidentally, the site of the attack was the same hand or leg that the patient had been injured recently or before. This inspired researchers to study how environmental factors such as localized nerve injury affect the initiation and spread of ALS.

The researchers used rats with the SOD1 gene mutation, which had higher levels of the SOD1 enzyme and had ALS-like symptoms, including progressive muscle weakness, starting at 15 weeks of age.

At 10 weeks of age, the researchers surgically injured individual nerves in the legs of SOD1 and wild-type rats. Although all the rats had reduced leg strength after surgery, the wild-type rats recovered almost completely within a few weeks. The SOD1 rats never recovered and developed weakness in the other leg.

They also found that in surgically injured rats, inflammation increased and lasted longer. And the number of microglia and astrocytes in the spinal cord region associated with damaged neurons also rose, the presence and spread of inflammation in these other cells to neighboring neurons at the same time.

This dispersion of inflammation may help explain why the disease first spreads from the site of injury. Microglia have many functions, but one of them is to prune or eliminate the synapses that connect one nerve cell to another. These connections are critical for normal function and neuron survival during development. Where there is inflammation of the spinal cord and an increase in microglia, you can see a tripling of the number of synapses. And once the nerve loses contact with its neighbor, neighboring cells often die.

This cascade of cell death may be responsible for the progressive spread of muscle weakness in ALS.

After understanding the relationship between peripheral nerve injury and the occurrence and spread of ALS through a new animal model, the researchers believe that the key to treating ALS is to stop the spread of the disease after the first time the disease begins. There are no treatments that significantly slow or prevent disease progression, and they are working hard to develop new drugs.
Cite this article

CUSABIO team. Can a nerve injury induce amyotrophic lateral sclerosis?.


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