Time course quantification of spastic hypertonia following spinal hemisection in rats

Hsieh, Tsung Hsun; Tsai, Jing-Jane; Wu, Yi-Ning; Hwang, Ing Shiou; Chen, Taibang; Chen, Jia-Jin Jason

doi:10.1016/j.neuroscience.2010.01.064

Cited by 15 publications

(17 citation statements)

References 64 publications

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“…Previously, we confirmed that this test enables to discriminate spasticity-strong and -weak rats after the injury by quantifying occurrence frequency of spastic behavior during the test. As is observed in the clinical time course, spastic behavior during swimming test increases in the subacute phase, 3-4 weeks after injury in rodent models [5][6][7]29 . At 4 weeks after injury in the present study, 70% vehicle-treated rats, as opposed to only 20% escitalopram-treated rats, manifested the spasticity-strong phenotype.…”

Section: Discussionmentioning

confidence: 57%

“…In human patients, characteristic spastic symptoms emerge around 2 months after SCI 4 . In spinalized rodent models, similar signs are observed, with progressive muscular stiffness and tail spasm starting 3-4 weeks after SCI 5,6 . To alleviate exaggerated muscle hyperactivity, a series of pharmacological drugs, such as gamma-aminobutyric acid (GABA) agonists, have been prescribed clinically; however, the need remains for more effective spasticity management 7 .…”

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confidence: 66%

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

Ryu

Ogata

Nagao

et al. 2021

Sci Rep

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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.

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Section: Discussionmentioning

confidence: 57%

mentioning

confidence: 66%

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

Ryu

Ogata

Nagao

et al. 2021

Sci Rep

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“…The study protocol included two operations. The first operation produced spinal cord injury (SCI) via right hemisection of the thoracic spinal cord , and the second operation applied treatment to the right L5 dorsal root ganglion 28 days later. Treatment was either PRF or a sham operation that used a posterior approach to the lumbar spine.…”

Section: Methodsmentioning

confidence: 99%

Reversible Spasticity Suppression and Locomotion Change After Pulsed Radiofrequency on the Dorsal Root Ganglia of Rats With Spinal Cord Injury

Chang

Lin

et al. 2019

Neuromodulation: Technology at the Neural Interface

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“…Hsieh та співавт. (2010) [113] спостерігали автогенне відновлення рухової функції задньої іпсилатеральної кінцівки до 11 (!) балів за шкалою ВВВ через 55 діб після висічення бічної половини спинного мозку (завдовжки 1-2 мм) у дорослих самців щурів на рівні хребців Т7-Т9 (на рівні сегмента Т8 спинного мозку) на тлі виразного контралатерального рухового дефіциту: наступної доби після травми функцію задньої контралатеральної кінцівки оцінили 3 балами за шкалою ВВВ, на 56-ту добу -15 балами.…”

Section: обговоренняunclassified

“…Схожий алгоритм використовували раніше за замовчуванням у контексті приведення темпорально різнорідних результатів до стандартизованої часової шкали [78][79][80][81][82][83][84][85]93,[98][99][100][101][102][103][104][105][106][107][108][109][110][111][112]. Оцінюючи з позиції наведених уточнень значення V ПФ і V ПС , а також результати порівняльного статистичного аналізу протягом першого місяця спостереження та через 6 і 7 тиж, 3 та 4 міс після травми, слід ураховувати, що, починаючи з 5-го тижня післятравматичного періоду, відрізки істотної тривалої односпрямованої динаміки на моделях ТСМ, які досліджували, зазвичай відсутні [62,64,94,[113][114][115].…”

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Model of spinal cord lateral hemi-excision at the lower thoracic level for the tasks of reconstructive and experimental neurosurgery

Medvediev¹,

Abdallah²,

Draguntsova³

et al. 2021

Ukr Neurosurg J

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Purpose. To test the model of spinal cord lateral hemiexcision in young rats. Materials and methods. Animals ‒ male rats (age about 1 month, body weight about 50 g, inbred derivatives of the Wistar line); the number of experimental groups is: 1) lateral spinal cord hemisection at the level of segments about T12–T13 (Sect; n=11); 2) lateral spinal cord hemiexcision about 1 mm long at the similar level (Exc; n=8). Assessment of motor Function Index (FI) and the Spasticity Index (SI) of the paretic hindlimb was carried out using the Basso–Beattie–Bresnahan (BBB) scale and Ashworth scale, respectively, in our technical modifications. The non-inclusion criteria: the BBB score above 9 points of FI for the ipsilateral hindlimb in a week after injury ‒and / or BBB score less than or equal to 14 points of FI of the contralateral hindlimb during a long follow-up period (in general, 2 animals in the Sect group, 3 animals ‒ in the Exc group). Asymptotic differences in the timing of testing between subgroups and groups were revealed during the first three weeks of follow-up. Interpolation reproduction of individual values of FI and SI was used in exceptional cases. The total follow-up period was 5 months. Statistical analysis was performed using the Mann-Whitney U Test, Wilcoxon Matched Pairs Test, Spearman’s Rank Order Correlation. For pathomorphological study, the method of silver impregnation of the spinal cord longitudinal sections of the Exc group animals obtained in 5 months after the simulation of injury was used. Results. One week after injury, the FI in the Sect group was 5.9±1.1 according to BBB points, a statistically significant increase in the FI lasted for the first 3 weeks (p<0.05; Wilcoxon Matched Pairs Test), the FI maximum in the group was 10.1±1.1 BBB points, and the FI value at the end of the study was 9.5±1.0 BBB points. In the Exc group, 1 week after injury, the FI was 0.9±0.5 BBB points, during the next week it reached the actual maximum (1.9±0.7 BBB points), by the end of the 5th month it significantly decreased to 0.8±0.3 BBB points (p<0.05; Wilcoxon Matched Pairs Test). One week after injury, the SI value in the Sect group was 0.3±0.1 points according to Ashworth scale, in the Exc group ‒ 0.7±0.1 Ashworth points, a significant increase (p<0.05; Wilcoxon Matched Pairs Test) in SI in the Sect group was noted during the 2nd week and the 2nd month, in the Exc group ‒ during the 2nd and 6th week, as well as the 3rd and 5th month after injury. The SI final and maximal score for the Sect group was 0.8±0.2 Ashworth points, and for the Exc group ‒ 3.6±0.3 Ashworth points. For both groups, there was no correlation between the mean FI value and a significant positive correlation of the mean SI value with the value of the follow-up period (p<0.05; Spearman’s Rank Order Correlation), as well as the absence of correlation between the mean FI and SI values during the total follow-up period. A significant negative correlation (p<0.05; Spearman’s Rank Order Correlation) between individual FI and SI values was found after 1 and 4 weeks, 3 and 5 months after the injury for the Sect group, as well as after 5, 7, 8 weeks and after 3 and 4 months for the Exc group. At all periods of follow-up, the difference in both FI and SI mean values of both groups was significant (p<0.05; the Mann-Whitney U Test). Conclusions. The studied model of spinal cord injury in young rats is the means of choice for testing solid neural transplantation means for the spinal cord injury restorative treatment. The interpretation of data obtained using the BBB scale on models of lateral half spinal cord injury should be carried out with caution, and the methodology for verifying spasticity requires significant improvement. We recommend that the optimal timing for the FI and SI monitoring after lateral half spinal cord injury is 7 days, 14 days and in 1, 2, 3, 4, 5, 6, and 7 months.

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Time course quantification of spastic hypertonia following spinal hemisection in rats

Cited by 15 publications

References 64 publications

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

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

Reversible Spasticity Suppression and Locomotion Change After Pulsed Radiofrequency on the Dorsal Root Ganglia of Rats With Spinal Cord Injury

Model of spinal cord lateral hemi-excision at the lower thoracic level for the tasks of reconstructive and experimental neurosurgery

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