Early escitalopram administration as a preemptive treatment strategy against spasticity after contusive spinal cord injury in rats

Abstract In the majority of spinal cord injury (SCI) patients, spasticity develops in the subacute phase and chronically persists with muscle hypertonia. Among various pathological conditions underlying spasticity, upregulated expression of 5-HT receptors (5-HTR) on the spinal motor neurons due to 5...

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Autores principales:	Youngjae Ryu, Toru Ogata, Motoshi Nagao, Yasuhiro Sawada, Ryohei Nishimura, Naoki Fujita
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f69cb93e96a341c7a8c62d60adc9ad1c
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spelling	oai:doaj.org-article:f69cb93e96a341c7a8c62d60adc9ad1c2021-12-02T14:23:23ZEarly escitalopram administration as a preemptive treatment strategy against spasticity after contusive spinal cord injury in rats10.1038/s41598-021-85961-52045-2322https://doaj.org/article/f69cb93e96a341c7a8c62d60adc9ad1c2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85961-5https://doaj.org/toc/2045-2322Abstract In the majority of spinal cord injury (SCI) patients, spasticity develops in the subacute phase and chronically persists with muscle hypertonia. Among various pathological conditions underlying spasticity, upregulated expression of 5-HT receptors (5-HTR) on the spinal motor neurons due to 5-HT denervation is considered one of crucial factors for hyperexcitability of the spinal circuit. As a 5-HT signal modulator, selective serotonin re-uptake inhibitors (SSRIs) are ordinarily prescribed for diseases associated with 5-HT in the CNS, and are known for their ability to increase 5-HT levels as well as to desensitize 5-HTR. Here, we hypothesized that early SSRI administration as a preemptive treatment strategy would effectively prevent the onset of spasticity. We used a rat model of contusive SCI and administered escitalopram during the first 4 weeks after injury, which is the period required for spasticity development in rodent models. We performed a swimming test to quantify spastic behaviors and conducted the Hoffman reflex test as well as histological analyses for 5-HT2AR and KCC2 expressions. Four weeks of escitalopram administration suppressed spastic behaviors during the swimming test and reduced the population of spasticity-strong rats. Moreover, the treatment resulted in decreased immunoreactivity of 5-HT2AR in the spinal motor neurons. Result of the H-reflex test and membrane expression of KCC2 were not significantly altered. In summary, early escitalopram administration could prevent the onset of spastic behaviors via regulation of 5-HT system after SCI, but could not modulate exaggerated spinal reflex. Our results suggest a novel application of SSRIs for preventative treatment of spasticity.Youngjae RyuToru OgataMotoshi NagaoYasuhiro SawadaRyohei NishimuraNaoki FujitaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Youngjae Ryu Toru Ogata Motoshi Nagao Yasuhiro Sawada Ryohei Nishimura Naoki Fujita Early escitalopram administration as a preemptive treatment strategy against spasticity after contusive spinal cord injury in rats
description	Abstract In the majority of spinal cord injury (SCI) patients, spasticity develops in the subacute phase and chronically persists with muscle hypertonia. Among various pathological conditions underlying spasticity, upregulated expression of 5-HT receptors (5-HTR) on the spinal motor neurons due to 5-HT denervation is considered one of crucial factors for hyperexcitability of the spinal circuit. As a 5-HT signal modulator, selective serotonin re-uptake inhibitors (SSRIs) are ordinarily prescribed for diseases associated with 5-HT in the CNS, and are known for their ability to increase 5-HT levels as well as to desensitize 5-HTR. Here, we hypothesized that early SSRI administration as a preemptive treatment strategy would effectively prevent the onset of spasticity. We used a rat model of contusive SCI and administered escitalopram during the first 4 weeks after injury, which is the period required for spasticity development in rodent models. We performed a swimming test to quantify spastic behaviors and conducted the Hoffman reflex test as well as histological analyses for 5-HT2AR and KCC2 expressions. Four weeks of escitalopram administration suppressed spastic behaviors during the swimming test and reduced the population of spasticity-strong rats. Moreover, the treatment resulted in decreased immunoreactivity of 5-HT2AR in the spinal motor neurons. Result of the H-reflex test and membrane expression of KCC2 were not significantly altered. In summary, early escitalopram administration could prevent the onset of spastic behaviors via regulation of 5-HT system after SCI, but could not modulate exaggerated spinal reflex. Our results suggest a novel application of SSRIs for preventative treatment of spasticity.
format	article
author	Youngjae Ryu Toru Ogata Motoshi Nagao Yasuhiro Sawada Ryohei Nishimura Naoki Fujita
author_facet	Youngjae Ryu Toru Ogata Motoshi Nagao Yasuhiro Sawada Ryohei Nishimura Naoki Fujita
author_sort	Youngjae Ryu
title	Early escitalopram administration as a preemptive treatment strategy against spasticity after contusive spinal cord injury in rats
title_short	Early escitalopram administration as a preemptive treatment strategy against spasticity after contusive spinal cord injury in rats
title_full	Early escitalopram administration as a preemptive treatment strategy against spasticity after contusive spinal cord injury in rats
title_fullStr	Early escitalopram administration as a preemptive treatment strategy against spasticity after contusive spinal cord injury in rats
title_full_unstemmed	Early escitalopram administration as a preemptive treatment strategy against spasticity after contusive spinal cord injury in rats
title_sort	early escitalopram administration as a preemptive treatment strategy against spasticity after contusive spinal cord injury in rats
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f69cb93e96a341c7a8c62d60adc9ad1c
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Early escitalopram administration as a preemptive treatment strategy against spasticity after contusive spinal cord injury in rats

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