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White matter may aid recovery from spinal cord injuries

Injuries, infections, and inflammatory diseases that damage the spinal cord can lead to intractable pain and disability. Some recovery is possible. The question is how best to encourage growth and healing of damaged nerves.

At the Vanderbilt University Institute for Imaging Sciences (VUIIS), scientists are focusing on a part of the brain and spinal cord that has so far been little studied: white matter. Their discoveries could lead to treatments that restore nerve activity through targeted delivery of electromagnetic stimuli or drugs.

Like the brain, the spinal cord is made up of nerve cell bodies (gray matter), which process sensation and control voluntary movement, and axons (white matter), fibers that connect nerve cells and project to the rest of the body.

In a recent article published in the journal proceedings of the National Academy of SciencesAnirban Sengupta, PhD, John Gore, PhD, and colleagues report detection of white matter signals in the spinal cord in response to a stimulus that are as robust as gray matter signals.

“In the spinal cord, the white matter signal is quite large and detectable, unlike in the brain, where it has less amplitude than the gray matter (signal),” said Sengupta, a research instructor in Radiology and Radiologic Sciences at Vanderbilt University Medical Center.

“This may be due to the larger volume of white matter in the spinal cord compared to the brain,” he added. Alternatively, the signal could represent “an intrinsic demand” on metabolism within white matter, reflecting its critical role in maintaining grey matter.

For several years, Gore, who directs VUIIS, and his colleagues have used functional magnetic resonance imaging (fMRI) to detect blood oxygenation level-dependent (BOLD) signals, a key marker of nervous system activity, in white matter.

Last year they reported that when people having their brains scanned using fMRI perform a task, such as moving their fingers, BOLD signals increase in white matter throughout the brain.

The current study monitored changes in BOLD signals in the spinal cord white matter at rest and in response to a vibrotactile stimulus applied to the fingers in an animal model. In response to stimulation, white matter activity was greatest in the ascending fiber “tracts” that carry the signal from the spinal cord to the brain.

This result is consistent with the known neurobiological function of white matter, the researchers said. White matter contains non-neuronal glial cells that do not produce electrical impulses but regulate blood flow and neurotransmitters, the signaling molecules that transmit signals between nerve cells.

There is still much to learn about the function of white matter in the spinal cord, but the findings from this research may help to better understand diseases that affect white matter in the spinal cord, including multiple sclerosis, Sengupta said.

“We’ll be able to see how white matter activity changes at different stages of the disease,” he said. Researchers will also be able to monitor the effectiveness of therapeutic interventions, including neuromodulation, in promoting recovery after spinal cord injury.

Sengupta, the paper’s corresponding author, earned his PhD from the Indian Institute of Technology in New Delhi in 2018 and joined the Vanderbilt faculty in 2024 after completing a postdoctoral fellowship at VUIIS.

Gore is a Distinguished Professor at the University of Radiology and Radiological Sciences, Biomedical Engineering, Molecular Physiology and Biophysics, and Physics and Astronomy. Other VUIIS co-authors were Arabinda Mishra, Feng Wang, PhD, and Li Min Chen, MD, PhD.

The study was funded by National Institutes of Health grants R01NS092961 and R01NS113832.