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Spatial-temporal characteristics of Cortical Reorganization after Spinal Cord Injury and the role of interneurons and astrocytes

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Understanding the physiological process of cortical reorganisation following a spinal cord injury

Research into the cortical reorganisation that happens after a spinal cord injury could open the door to new treatments.

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A spinal cord injury (SCI) occurs when a blow or a cut to the spine interrupts the sensory information travelling to the brain. This interruption initiates cortical reorganisation (CoRe), a process where neuronal activity from adjacent, intact cortical regions increases and expands towards the deafferented cortical area. “Although CoRe is crucial for the functional recovery of SCI patients, when exacerbated, it can trigger such pathologies as neuropathic pain, phantom sensation, and spasticity – all of which can result in a decrease in quality of life,” says Juliana Rosa, a researcher from the experimental neurophysiology and neuronal circuits lab at SESCAM (website in Spanish). With the support of the EU-funded CRASCI project, Rosa, along with colleague Juan Aguilar, are leading an effort to better understand the mechanisms behind CoRe. “Knowing the mechanisms by which CoRe occurs is key to generating new therapeutic strategies that promote and/or limit its extension following an SCI or other traumatic brain injury,” adds Aguilar.

New insights into neuronal activity

To start, the project, which received support from the Marie Skłodowska-Curie Actions programme, studied how an SCI changes the neuronal activity happening within the cortical areas that receive information from body regions located below the injury. What they found was the existence of a layering-dependent mechanism, with layer 2/3 of the cerebral cortex underlying the most significant increase in CoRe activity. “This result is important as layer 2/3 undergoes most of the connectivity between distinct brain areas and, as such, could be key to controlling reorganisation,” explains Rosa. Next, researchers looked at whether changes in neuronal activity were mediated by simultaneous alterations of inhibitory neurons. “Using anatomical techniques, we discovered that inhibitory synapses on excitatory L5 neurons increase after an SCI,” remarks Aguilar. “This in turn leads to a decrease in excitability.” The project also genetically manipulated astrocytes. “This work demonstrated that these glial cells modulate neuronal expansion and could therefore be used as a therapeutical target to enhance or limit CoRe,” adds Rosa.

A giant step in the field

Taken together, all these findings shed new light on the physiological process of CoRe that happens after a SCI. “Prior to this work, CoRe had only been observed as a process that takes place within the inaccessible black box of the brain,” notes Aguilar. “Being able to identify the role that the different layers and cellular elements play in CoRe is a giant step in our field – and towards being able to better treat spinal cord injuries.” The project is now working on the selective manipulation of different cellular populations. “This manipulation could help avoid the development of common pathologies, thus improving sensorimotor functions and patient recovery,” concludes Rosa.

Keywords

CRASCI, cortical reorganisation, CoRe, spinal cord injury, SCI, brain, traumatic brain injury, neuronal activity, cerebral cortex, neurons

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