May 04, 2023, Kitchener, Ontario
Posted by: Robert Deutschmann, Personal Injury Lawyer
Spinal cord injury (SCI) can result in serious disability including the loss of use of legs arms or both. Contrary to common thought, most spinal cord injuries don’t completely sever the spine. This means that some nerve impulses are able to travel back and forth. What happens though is that the connection becomes dormant.
Research is now being done to determine if deep brain stimulation or electrical stimulation can help activate the connection. The problem being worked on is which part of the brain needs to be targeted.
Dr. Frederic Bretzner at Universite Laval is working to solve this problem. You can read his work in Cell Reports Medicine. The value of the research is immense. Reactivating the nerve transmissions will improve the lives of those with SCI, other trauma, and neurodegenerative disease like Parkinson’s, ALS and stroke.
You can read the full article here in Cell Reports Medicine
This is the Summary and Introduction:
Functional contribution of mesencephalic locomotor region nuclei to locomotor recovery after spinal cord injury
Marie Roussel,1 David Lafrance-Zoubga,1 Nicolas Josset,1 Maxime Lemieux,1 and Frederic Bretzner1,2,3,* 1Centre de Recherche du CHU de Que´bec, CHUL-Neurosciences, 2705 Boul. Laurier, Que´bec, QC G1V 4G2, Canada 2Faculty of Medicine, Department of Psychiatry and Neurosciences, Universite´ Laval, Que´bec, QC G1V 4G2, Canada 3Lead contact *Correspondence: email@example.com https://doi.org/10.1016/j.xcrm.2023.100946
SUMMARY Spinal cord injury (SCI) results in a disruption of information between the brain and the spinal circuit. Electrical stimulation of the mesencephalic locomotor region (MLR) can promote locomotor recovery in acute and chronic SCI rodent models. Although clinical trials are currently under way, there is still debate about the organization of this supraspinal center and which anatomic correlate of the MLR should be targeted to promote recovery. Combining kinematics, electromyographic recordings, anatomic analysis, and mouse genetics, our study reveals that glutamatergic neurons of the cuneiform nucleus contribute to locomotor recovery by enhancing motor efficacy in hindlimb muscles, and by increasing locomotor rhythm and speed on a treadmill, over ground, and during swimming in chronic SCI mice. In contrast, glutamatergic neurons of the pedunculopontine nucleus slow down locomotion. Therefore, our study identifies the cuneiform nucleus and its glutamatergic neurons as a therapeutical target to improve locomotor recovery in patients living with SCI.
INTRODUCTION Although the spinal cord contains all the circuitry necessary for locomotion, people with spinal cord injury (SCI) are unable to walk due to the absence of commands from the brain. Motor recovery can be partially achieved by rehabilitative training and neuromodulatory therapies intended to promote the descending motor command from the brain to the spinal cord after SCI.1–7 Recently, deep brain stimulation of the mesencephalic locomotor region (MLR), a supraspinal locomotor center, has been shown to improve locomotor functions in rats with chronic but incomplete SCI with even a few spared axonal fibers.6–8 Interestingly, these functional changes come with an extensive reorganization in the brainstem region after SCI,9 thus supporting the important contribution of the MLR to locomotor recovery after incomplete SCI. The anatomic correlate of this functional region has been initially identified as the cuneiform nucleus (CnF), a cluster of glutamatergic neurons, and the pedunculopontine nucleus (PPN), a cluster of glutamatergic and cholinergic neurons. Despite a growing body of evidence from mouse genetics studies,10–18 there is still debate about the exact anatomic correlate of this supraspinal locomotor center. Previously, using a headrestrained mouse on an air-lifted ball,19,20 it was shown that optogenetic stimulation of glutamatergic neurons of the MLR (including the CnF and PPN) can generate locomotion in contrast to cholinergic or GABAergic MLR neurons. More recently, using smaller volumes of adeno-associated virus to circumscribe photostimulation to a nucleus of interest, it was shown that glutamatergic CnF neurons can initiate locomotion in freely behaving mice,10,11,15 whereas glutamatergic PPN neurons exhibit higher variability in generating locomotion.10,11,14–16 Furthermore, glutamatergic CnF neurons accelerate locomotor rhythm and speed during ongoing locomotion, whereas glutamatergic PPN neurons only prolong the stance phase, contributing to postural adjustments and slowing locomotor rhythm in normal conditions.10,15 Although cholinergic PPN neurons were initially reported to increase speed during head-restrained locomotion,20 more recent studies suggest that they do not actually modulate locomotor speed in freely behaving mice.10,11 Although deep brain stimulation (DBS) in the PPN7 or the CnF8 can improve locomotor recovery in animal models of SCI, there are still questions about which neuronal population is the most efficient. With ongoing clinical trials aiming to assess DBS in the vicinity of the MLR of patients with incomplete SCI,21 it is now urgent to gain a better understanding of how these distinct neuronal populations of the midbrain can contribute to and promote functional locomotor recovery after SCI.