Sex may influence motor phenotype in a novel rodent model of cerebral palsy
Cerebral palsy (CP) is the most common cause of childhood motor disability, manifesting most often as spasticity and/or dystonia. Spasticity and dystonia are often co-morbid clinically following severe injury at term gestation. Currently available animal CP models have not demonstrated or differenti...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-02-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996119303869 |
| _version_ | 1818827623533379584 |
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| author | Bhooma R. Aravamuthan Sushma Gandham Anne B. Young Seward B. Rutkove |
| author_facet | Bhooma R. Aravamuthan Sushma Gandham Anne B. Young Seward B. Rutkove |
| author_sort | Bhooma R. Aravamuthan |
| collection | DOAJ |
| description | Cerebral palsy (CP) is the most common cause of childhood motor disability, manifesting most often as spasticity and/or dystonia. Spasticity and dystonia are often co-morbid clinically following severe injury at term gestation. Currently available animal CP models have not demonstrated or differentiated between these two motor phenotypes, limiting their clinical relevance. We sought to develop an animal CP model displaying objectively identifiable spasticity and dystonia. We exposed rat pups at post-natal day 7–8 (equivalent to human 37 post-conceptional weeks) to global hypoxia. Since spasticity and dystonia can be difficult to differentiate from each other in CP, objective electrophysiologic markers of motor phenotypes were assessed. Spasticity was inferred using an electrophysiologic measure of hyperreflexia: soleus Hoffman reflex suppression with 2 Hz tibial nerve stimulation. Dystonia was assessed during voluntary isometric hindlimb withdrawal at different levels of arousal by calculating tibialis anterior and triceps surae electromyographic co-activation as a surrogate of overflow muscle activity. Hypoxia affected spasticity and dystonia measures in a sex-dependent manner. Males had attenuated Hoffman reflex suppression suggestive of spasticity but no change in antagonist muscle co-activation. In contrast, females demonstrated increased co-activation suggestive of dystonia but no change in Hoffman reflex suppression. Therefore, there was an unexpected segregation of electrophysiologically-defined motor phenotypes based on sex with males predominantly demonstrating spasticity and females predominantly demonstrating dystonia. These results require human clinical confirmation but suggest that sex could play a critical role in the motor manifestations of neonatal brain injury. |
| first_indexed | 2024-12-19T00:46:30Z |
| format | Article |
| id | doaj.art-a575b38ab77649a481cd12479b57da33 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-19T00:46:30Z |
| publishDate | 2020-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-a575b38ab77649a481cd12479b57da332022-12-21T20:44:15ZengElsevierNeurobiology of Disease1095-953X2020-02-01134Sex may influence motor phenotype in a novel rodent model of cerebral palsyBhooma R. Aravamuthan0Sushma Gandham1Anne B. Young2Seward B. Rutkove3Washington University in St. Louis School of Medicine, St. Louis, MO, USA; Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Corresponding author at: Department of Neurology, Division of Pediatric Neurology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8111, St. Louis, MO 63110-1093, USA.Washington University in St. Louis School of Medicine, St. Louis, MO, USAHarvard Medical School, Boston, MA, USA; Massachusetts General Hospital, Boston, MA, USAHarvard Medical School, Boston, MA, USA; Beth Israel Deaconess Medical Center, Boston, MA, USACerebral palsy (CP) is the most common cause of childhood motor disability, manifesting most often as spasticity and/or dystonia. Spasticity and dystonia are often co-morbid clinically following severe injury at term gestation. Currently available animal CP models have not demonstrated or differentiated between these two motor phenotypes, limiting their clinical relevance. We sought to develop an animal CP model displaying objectively identifiable spasticity and dystonia. We exposed rat pups at post-natal day 7–8 (equivalent to human 37 post-conceptional weeks) to global hypoxia. Since spasticity and dystonia can be difficult to differentiate from each other in CP, objective electrophysiologic markers of motor phenotypes were assessed. Spasticity was inferred using an electrophysiologic measure of hyperreflexia: soleus Hoffman reflex suppression with 2 Hz tibial nerve stimulation. Dystonia was assessed during voluntary isometric hindlimb withdrawal at different levels of arousal by calculating tibialis anterior and triceps surae electromyographic co-activation as a surrogate of overflow muscle activity. Hypoxia affected spasticity and dystonia measures in a sex-dependent manner. Males had attenuated Hoffman reflex suppression suggestive of spasticity but no change in antagonist muscle co-activation. In contrast, females demonstrated increased co-activation suggestive of dystonia but no change in Hoffman reflex suppression. Therefore, there was an unexpected segregation of electrophysiologically-defined motor phenotypes based on sex with males predominantly demonstrating spasticity and females predominantly demonstrating dystonia. These results require human clinical confirmation but suggest that sex could play a critical role in the motor manifestations of neonatal brain injury.http://www.sciencedirect.com/science/article/pii/S0969996119303869Cerebral palsyNeonatal brain injuryDystoniaSpasticityAnimal models of disease |
| spellingShingle | Bhooma R. Aravamuthan Sushma Gandham Anne B. Young Seward B. Rutkove Sex may influence motor phenotype in a novel rodent model of cerebral palsy Neurobiology of Disease Cerebral palsy Neonatal brain injury Dystonia Spasticity Animal models of disease |
| title | Sex may influence motor phenotype in a novel rodent model of cerebral palsy |
| title_full | Sex may influence motor phenotype in a novel rodent model of cerebral palsy |
| title_fullStr | Sex may influence motor phenotype in a novel rodent model of cerebral palsy |
| title_full_unstemmed | Sex may influence motor phenotype in a novel rodent model of cerebral palsy |
| title_short | Sex may influence motor phenotype in a novel rodent model of cerebral palsy |
| title_sort | sex may influence motor phenotype in a novel rodent model of cerebral palsy |
| topic | Cerebral palsy Neonatal brain injury Dystonia Spasticity Animal models of disease |
| url | http://www.sciencedirect.com/science/article/pii/S0969996119303869 |
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