Altered Motoneuron Properties Contribute to Motor Deficits in a Rabbit Hypoxia-Ischemia Model of Cerebral Palsy

Altered Motoneuron Properties Contribute to Motor Deficits in a Rabbit Hypoxia-Ischemia Model of Cerebral Palsy

Cerebral palsy (CP) is caused by a variety of factors attributed to early brain damage, resulting in permanently impaired motor control, marked by weakness and muscle stiffness. To find out if altered physiology of spinal motoneurons (MNs) could contribute to movement deficits, we performed whole-ce...

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Published in:Frontiers in cellular neuroscience Vol. 14; p. 69
Main Authors: Steele, Preston R, Cavarsan, Clarissa Fantin, Dowaliby, Lisa, Westefeld, Megan, Katenka, N, Drobyshevsky, Alexander, Gorassini, Monica A, Quinlan, Katharina A
Format: Journal Article
Language:English
Published: Switzerland Frontiers Research Foundation 25-03-2020
Frontiers Media S.A
Subjects:
Brain injury
Catheters
Cellular Neuroscience
Cerebral palsy
Electrodes
Excitability
Firing pattern
frequency-current
Genotype & phenotype
Gestation
Hypoxia
hypoxia-ischemia
Ischemia
Laboratory animals
Membrane potential
Motor neurons
Motor task performance
Neonates
Neurons
Paralysis
persistent inward current
Phenotypes
rabbit
Rabbits
Software
Spasticity
Spinal cord
Spinal cord injuries
Variance analysis
cerebral palsy
hypoxia-ischemia
persistent inward current
rabbit
frequency-current
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Summary:Cerebral palsy (CP) is caused by a variety of factors attributed to early brain damage, resulting in permanently impaired motor control, marked by weakness and muscle stiffness. To find out if altered physiology of spinal motoneurons (MNs) could contribute to movement deficits, we performed whole-cell patch-clamp in neonatal rabbit spinal cord slices after developmental injury at 79% gestation. After preterm hypoxia-ischemia (HI), rabbits are born with motor deficits consistent with a spastic phenotype including hypertonia and hyperreflexia. There is a range in severity, thus kits are classified as severely affected, mildly affected, or unaffected based on modified Ashworth scores and other behavioral tests. At postnatal day (P)0-5, we recorded electrophysiological parameters of 40 MNs in transverse spinal cord slices using whole-cell patch-clamp. We found significant differences between groups (severe, mild, unaffected and sham control MNs). Severe HI MNs showed more sustained firing patterns, depolarized resting membrane potential, and fired action potentials at a higher frequency. These properties could contribute to muscle stiffness, a hallmark of spastic CP. Interestingly altered persistent inward currents (PICs) and morphology in severe HI MNs would dampen excitability (depolarized PIC onset and increased dendritic length). In summary, changes we observed in spinal MN physiology likely contribute to the severity of the phenotype, and therapeutic strategies for CP could target the excitability of spinal MNs.
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Reviewed by: Randall Keith Powers, University of Washington, United States; Nina L. Suresh, Rehabilitation Institute of Chicago, United States
Edited by: Rustem Khazipov, Institut National de la Santé et de la Recherche Médicale (INSERM), France
ISSN:1662-5102
1662-5102
DOI:10.3389/fncel.2020.00069