Tag: axon

Categories : NeurologyTags :

White Matter may Aid Recovery from Spinal Cord Injuries

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View of the spinal cord. Credit: Scientific Animations CC4.0

Injuries, infection and inflammatory diseases that damage the spinal cord can lead to intractable pain and disability but some degree of recovery may be possible. The question is, how best to stimulate the regrowth and healing of damaged nerves.

At the Vanderbilt University Institute of Imaging Science (VUIIS), scientists are focusing on a previously understudied part of the brain and spinal cord – white matter, which is made up of axons that relay signals. Their discoveries could lead to treatments that restore nerve activity through the targeted delivery of electromagnetic stimuli or drugs.

In a recent paper published in the Proceedings of the National Academy of Sciences, Anirban Sengupta, PhD, John Gore, PhD, and their colleagues report the detection of signals from white matter in the spinal cord in response to a stimulus that are as robust as grey 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 grey matter (signal),” said Sengupta, research instructor in Radiology and Radiological 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” in metabolism within the white matter, reflecting its critical role in supporting grey matter.

For several years, Gore, who directs the 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 participants undergoing fMRI perform a task, like wiggling their fingers, BOLD signals increase in white matter throughout the brain.

The current study monitored changes in BOLD signals in the white matter of the spinal cord 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 higher in “tracts” of ascending fibres that carry the signal from the spine to the brain.

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

Much remains to be learned about the function of white matter in the spinal cord. But the findings from this research may help in improved understanding of diseases that affect white matter in the spinal cord, including multiple sclerosis, Sengupta said.

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

Source: Vanderbilt University Medical Center

Categories : NeurologyTags :

Scientists Record Powerful Signals in the Brain’s White Matter

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Scientists have concentrated on the grey matter of the cortex, composed of nerve cell bodies , while ignoring white matter, composed of axons, even though it makes up half the brain. Now, in the Proceedings of the National Academy of Sciences, Vanderbilt University researchers report strong signs of brain activity when performing certain tasks.

For several years, John Gore, PhD, director of the Vanderbilt University Institute of Imaging Science, and his colleagues have used functional magnetic resonance imaging (fMRI) to detect blood oxygenation-level dependent (BOLD) signals, a key marker of brain activity, in white matter.

In this latest paper, the researchers report that when people who are having their brains scanned by fMRI perform a task, like wiggling their fingers, BOLD signals increase in white matter throughout the brain.

“We don’t know what this means,” said the paper’s first author, Kurt Schilling, PhD, research assistant professor of Radiology and Radiological Sciences at VUMC. “We just know that something is happening. There truly is a powerful signal in the white matter.”

It is important to pursue this because disorders as diverse as epilepsy and multiple sclerosis disrupt the “connectivity” of the brain, Schilling said. This suggests that something is going on in white matter.

To find out, the researchers will continue to study changes in white matter signals they’ve previously detected in schizophrenia, Alzheimer’s disease and other brain disorders. Through animal studies and tissue analysis, they also hope to determine the biological basis for these changes.

In grey matter, BOLD signals reflect a rise in blood flow (and oxygen) in response to increased nerve cell activity.

Perhaps the axons, or the glial cells that maintain the protective myelin sheath around them, also use more oxygen when the brain is ‘working’. Or perhaps these signals are somehow related to what’s going on in the grey matter.

But even if nothing biological is going on in white matter, “there’s still something happening here,” Schilling said. “The signal is changing. It’s changing differently in different white matter pathways and it’s in all white matter pathways, which is a unique finding.”

One reason that white matter signals have been understudied is that they have lower energy than grey matter signals, and thus are more difficult to distinguish from the brain’s background “noise.”

The VUMC researchers boosted the signal-to-noise ratio by having the person whose brain was being scanned repeat a visual, verbal or motor task many times to establish a trend and by averaging the signal over many different white matter fibre pathways.

“For 25 or 30 years, we’ve neglected the other half of the brain,” Schilling said. Some researchers not only have ignored white matter signals but have removed them from their reports of brain function.

The Vanderbilt findings suggest that many fMRI studies thus “may not only underestimate the true extent of brain activation, but also … may miss crucial information from the MRI signal,” the researchers concluded.

Source: Vanderbilt University

Categories : Neurology Regenerative MedicineTags :

Neuroscientists Regenerate Neurons in Mice with Spinal Cord Injury

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Source: CC0

In a new study using mice, neuroscientists have uncovered a crucial component for restoring functional activity after spinal cord injury. In the study, published in Science, the researchers showed that re-growing specific neurons back to their natural target regions led to recovery, while random regrowth was not effective.

In a 2018 study in Nature, the team identified a treatment approach that triggers axons to regrow after spinal cord injury in rodents. But even as that approach successfully led to the regeneration of axons across severe spinal cord lesions, achieving functional recovery remained a significant challenge.

For the new study, the team of researchers from UCLA, the Swiss Federal Institute of Technology, and Harvard University aimed to determine whether directing the regeneration of axons from specific neuronal subpopulations to their natural target regions could lead to meaningful functional restoration after spinal cord injury in mice. They first used advanced genetic analysis to identify nerve cell groups that enable walking improvement after a partial spinal cord injury.

The researchers then found that merely regenerating axons from these nerve cells across the spinal cord lesion without specific guidance had no impact on functional recovery. However, when the strategy was refined to include using chemical signals to attract and guide the regeneration of these axons to their natural target region in the lumbar spinal cord, significant improvements in walking ability were observed in a mouse model of complete spinal cord injury.

“Our study provides crucial insights into the intricacies of axon regeneration and requirements for functional recovery after spinal cord injuries,” said Michael Sofroniew, MD, PhD, professor of neurobiology at the David Geffen School of Medicine at UCLA and a senior author of the new study. “It highlights the necessity of not only regenerating axons across lesions but also of actively guiding them to reach their natural target regions to achieve meaningful neurological restoration.”

The authors say understanding that re-establishing the projections of specific neuronal subpopulations to their natural target regions holds significant promise for the development of therapies aimed at restoring neurological functions in larger animals and humans. However, the researchers also acknowledge the complexity of promoting regeneration over longer distances in non-rodents, necessitating strategies with intricate spatial and temporal features. Still, they conclude that applying the principles laid out in their work “will unlock the framework to achieve meaningful repair of the injured spinal cord and may expedite repair after other forms of central nervous system injury and disease.”

Source: University of California – Los Angeles Health Sciences