• Posted April 29, 2024

Spinal Cord Injury Damages Metabolism, and Scientists Now Know Why

Patients with a spinal cord injury frequently develop diabetes and heart health problems, and researchers now think they know why.

It appears that neuron activity following the injury causes belly fat to break down into compounds that leak and pool in the liver and other organs, a new animal study has discovered.

“These are quite rapid changes. As soon as we disrupt sensory processing as a result of spinal cord injury, we see changes in the fat,” said senior study author Andrea Tedeschi, an assistant professor of neuroscience in Ohio State University's College of Medicine.

This causes a “chain of reactions -- triglycerides start breaking down into glycerol and free fatty acids that are released in circulation and taken up by the liver, the heart, the muscles, and accumulating, setting up conditions for insulin resistance,” Tedeschi added in a university news release.

The team also has identified a potential treatment to ward off illnesses caused by this phenomenon: The seizure medication gabapentin prevented these damaging metabolic effects from spinal cord injuries in lab mice.

Gabapentin inhibits a neurotransmitter that becomes overactive and causes communication problems within the body following damage to the nervous system, researchers explained.

“Through administration of gabapentin, we were able to normalize metabolic function,” Tedeschi said.

Heart disease and type 2 diabetes are among the leading causes of death in people with a spinal cord injury, researchers explained in background notes. 

Researchers suspected these disorders might be related to dysfunction in the regulation of belly fat, which has a complex metabolic role.

Such fat -- also called adipose tissue -- stores energy and releases fatty acids as needed for fuel, helping keep blood sugar levels on an even keel, researchers said.

Sensory nerves regularly send messages to fat tissue under healthy conditions, so researchers suspected they might play a role in these health problems.

Lab mice were given a spinal cord injury that affected only the sensory nerves but did not interrupt the sympathetic “fight-or-flight” nervous system.

Experiments revealed a cascade of abnormal activity within seven days after the injury, with the sensory nerves firing off signals to fat tissue. Tedeschi calls it “a maladaptive reorganization of the sensory system.”

In response to these signals, the fat starts breaking down, flooding the blood and organs with fatty acids and glycerol in a process that quickly spins out of control.

“A vicious cycle is established -- it’s almost like you’re pressing the gas pedal so your car can run out of gas but someone else continues to refill the tank, so it never runs out,” Tedeschi explained.

Gabapentin previously has been shown to restore limb function in animals after a spinal cord injury, and it has also boosted stroke recovery, researchers said.

Giving lab mice a high dose of gabapentin and then tapering off prevented the spillover of fatty acids into the liver, causing their metabolism to revert to normal, researchers found.

Within four weeks, mice had normal metabolism without the drug, results show.

“This way, we were able to normalize metabolism to a condition much more similar to control mice,” said lead study author Debasish Roy, a postdoctoral researcher in Tedeschi’s lab. “This suggests that as we discontinue administration of the drug, we retain beneficial action and prevent spillover of lipids in the liver. That was really exciting.”

The findings suggest that prescribing gabapentin soon after a spinal cord injury might protect against the health problems that often occur, Tedeschi said.

Of course, caution is needed in interpreting these results, since findings in animals do not always pan out in humans.

The new study was published April 24 in the journal Cell Reports Medicine.

More information

The National Institutes of Health have more about spinal cord injury.

SOURCE: Ohio State University, news release