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Brain : a Journal of Neurology May 2020Rehabilitative exercise in humans with spinal cord injury aims to engage residual neural networks to improve functional recovery. We hypothesized that exercise combined... (Randomized Controlled Trial)
Randomized Controlled Trial
Rehabilitative exercise in humans with spinal cord injury aims to engage residual neural networks to improve functional recovery. We hypothesized that exercise combined with non-invasive stimulation targeting spinal synapses further promotes functional recovery. Twenty-five individuals with chronic incomplete cervical, thoracic, and lumbar spinal cord injury were randomly assigned to 10 sessions of exercise combined with paired corticospinal-motor neuronal stimulation (PCMS) or sham-PCMS. In an additional experiment, we tested the effect of PCMS without exercise in 13 individuals with spinal cord injury with similar characteristics. During PCMS, 180 pairs of stimuli were timed to have corticospinal volleys evoked by transcranial magnetic stimulation over the primary motor cortex arrive at corticospinal-motor neuronal synapses of upper- or lower-limb muscles (depending on the injury level), 1-2 ms before antidromic potentials were elicited in motor neurons by electrical stimulation of a peripheral nerve. Participants exercised for 45 min after all protocols. We found that the time to complete subcomponents of the Graded and Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) and the 10-m walk test decreased on average by 20% after all protocols. However, the amplitude of corticospinal responses elicited by transcranial magnetic stimulation and the magnitude of maximal voluntary contractions in targeted muscles increased on overage by 40-50% after PCMS combined or not with exercise but not after sham-PCMS combined with exercise. Notably, behavioural and physiological effects were preserved 6 months after the intervention in the group receiving exercise with PCMS but not in the group receiving exercise combined with sham-PCMS, suggesting that the stimulation contributed to preserve exercise gains. Our findings indicate that targeted non-invasive stimulation of spinal synapses might represent an effective strategy to facilitate exercise-mediated recovery in humans with different degrees of paralysis and levels of spinal cord injury.
Topics: Adult; Aged; Electric Stimulation Therapy; Evoked Potentials, Motor; Exercise Therapy; Female; Humans; Male; Middle Aged; Motor Cortex; Motor Neurons; Neuronal Plasticity; Pyramidal Tracts; Recovery of Function; Spinal Cord Injuries; Transcranial Magnetic Stimulation; Young Adult
PubMed: 32355959
DOI: 10.1093/brain/awaa052 -
Cell Metabolism Mar 2020Axonal regeneration in the central nervous system (CNS) is a highly energy-demanding process. Extrinsic insults and intrinsic restrictions lead to an energy crisis in...
Axonal regeneration in the central nervous system (CNS) is a highly energy-demanding process. Extrinsic insults and intrinsic restrictions lead to an energy crisis in injured axons, raising the question of whether recovering energy deficits facilitates regeneration. Here, we reveal that enhancing axonal mitochondrial transport by deleting syntaphilin (Snph) recovers injury-induced mitochondrial depolarization. Using three CNS injury mouse models, we demonstrate that Snph mice display enhanced corticospinal tract (CST) regeneration passing through a spinal cord lesion, accelerated regrowth of monoaminergic axons across a transection gap, and increased compensatory sprouting of uninjured CST. Notably, regenerated CST axons form functional synapses and promote motor functional recovery. Administration of the bioenergetic compound creatine boosts CST regenerative capacity in Snph mice. Our study provides mechanistic insights into intrinsic regeneration failure in CNS and suggests that enhancing mitochondrial transport and cellular energetics are promising strategies to promote regeneration and functional restoration after CNS injuries.
Topics: Animals; Axonal Transport; Axons; Biogenic Monoamines; Cervical Vertebrae; Creatine; Energy Metabolism; Membrane Proteins; Mice, Inbred C57BL; Mitochondria; Motor Neurons; Nerve Regeneration; Nerve Tissue Proteins; Pyramidal Tracts; Recovery of Function; Spinal Cord Injuries
PubMed: 32130884
DOI: 10.1016/j.cmet.2020.02.002 -
Current Opinion in Neurobiology Dec 2023Corticostriatal pathways are essential for a multitude of motor, sensory, cognitive, and affective functions. They are mediated by cortical pyramidal neurons, roughly... (Review)
Review
Corticostriatal pathways are essential for a multitude of motor, sensory, cognitive, and affective functions. They are mediated by cortical pyramidal neurons, roughly divided into two projection classes: the pyramidal tract (PT) and the intratelencephalic tract (IT). These pathways have been the focus of numerous studies in recent years, revealing their distinct structural and functional properties. Notably, their synaptic connectivity within ipsi- and contralateral cortical and striatal microcircuits is characterized by a high degree of target selectivity, providing a means to regulate the local neuromodulatory landscape in the striatum. Here, we discuss recent findings regarding the functional organization of the PT and IT corticostriatal pathways and its implications for bilateral sensorimotor functions.
Topics: Neurons; Corpus Striatum; Pyramidal Cells; Pyramidal Tracts; Neural Pathways; Cerebral Cortex
PubMed: 37696188
DOI: 10.1016/j.conb.2023.102781 -
International Journal of Molecular... Jan 2022To date, there is no overarching proposition for the ontogenetic-neurobiological basis of self-regulation. This paper suggests that the balanced self-regulatory reaction... (Review)
Review
To date, there is no overarching proposition for the ontogenetic-neurobiological basis of self-regulation. This paper suggests that the balanced self-regulatory reaction of the fetus, newborn and infant is based on a complex mechanism starting from early brainstem development and continuing to progressive control of the cortex over the brainstem. It is suggested that this balance occurs through the synchronous reactivity between the sympathetic and parasympathetic systems, both which originate from the brainstem. The paper presents an evidence-based approach in which molecular excitation-inhibition balance, interchanges between excitatory and inhibitory roles of neurotransmitters as well as cardiovascular and white matter development across gestational ages, are shown to create sympathetic-parasympathetic synchrony, including the postnatal development of electroencephalogram waves and vagal tone. These occur in developmental milestones detectable in the same time windows (sensitive periods of development) within a convergent systematic progress. This ontogenetic stepwise process is termed "the self-regulation clock" and suggest that this clock is located in the largest connection between the brainstem and the cortex, the corticospinal tract. This novel evidence-based new theory paves the way towards more accurate hypotheses and complex studies of self-regulation and its biological basis, as well as pointing to time windows for interventions in preterm infants. The paper also describes the developing indirect signaling between the suprachiasmatic nucleus and the corticospinal tract. Finally, the paper proposes novel hypotheses for molecular, structural and functional investigation of the "clock" circuitry, including its associations with other biological clocks. This complex circuitry is suggested to be responsible for the developing self-regulatory functions and their neurobehavioral correlates.
Topics: Biological Clocks; Cardiovascular System; Electroencephalography; Female; Gestational Age; Humans; Infant; Infant, Newborn; Pregnancy; Pyramidal Tracts; Suprachiasmatic Nucleus
PubMed: 35055184
DOI: 10.3390/ijms23020993