l-Dopa effect on frequency-dependent depression of the H-reflex in adult rats with complete spinal cord transection

Líu, Hao; Skinner, R.D.; Arfaj, A.; Yates, Charlotte; Reese, N.B.; Williams, Keith D.; García‐Rill, Edgar

doi:10.1016/j.brainresbull.2010.07.005

Cited by 15 publications

(5 citation statements)

References 44 publications

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“…It was previously reported that a BWSTT for up 8 weeks induced a restoration of the RDD in animal with a thoracic contusion injury . Similar results were obtained with 1 month (2 × 30 min bouts of cycling with a 10 min rest, 5 days/week), 1.5 months (1 h/day, 5 days/week), 3 months (1 h/day, 5 days/week), or 4 months (15 min/day, 5 days/week) of passive motorized bicycle exercise training started immediately or with a delay of 30 days after a spinal cord transection in which the onset of hyperreflexia is after the seventh day postinjury. ,,,− It was observed that the effect of the exercise persisted after the end of the training protocol, and it was concluded that the RDD recovery was correlated with an increase in neurotrophic factor proteins (BDNF, NT-3, and NT-4) ,− and an increase of BDNF upregulating KCC2 expression and restoring RDD after SCI . However, it was noted that only step-training generated by spinal networks triggered by afferent feedback increased GDNF levels .…”

Section: Discussionsupporting

confidence: 82%

Delayed Injection of a Physically Cross-Linked PNIPAAm-g-PEG Hydrogel in Rat Contused Spinal Cord Improves Functional Recovery

et al. 2020

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Spinal cord injury is a main health issue, leading to multiple functional deficits with major consequences such as motor and sensitive impairment below the lesion. To date, all repair strategies remain ineffective. In line with the experiments showing that implanted hydrogels, immunologically inert biomaterials, from natural or synthetic origins, are promising tools and in order to reduce functional deficits, to increase locomotor recovery, and to reduce spasticity, we injected into the lesion area, 1 week after a severe T10 spinal cord contusion, a thermoresponsive physically cross-linked poly(N-isopropylacrylamide)-poly(ethylene glycol) copolymer hydrogel. The effect of postinjury intensive rehabilitation training was also studied. A group of male Sprague–Dawley rats receiving the hydrogel was enrolled in an 8 week program of physical activity (15 min/day, 5 days/week) in order to verify if the combination of a treadmill step-training and hydrogel could lead to better outcomes. The data obtained were compared to those obtained in animals with a spinal lesion alone receiving a saline injection with or without performing the same program of physical activity. Furthermore, in order to verify the biocompatibility of our designed biomaterial, an inflammatory reaction (interleukin-1β, interleukin-6, and tumor necrosis factor-α) was examined 15 days post-hydrogel injection. Functional recovery (postural and locomotor activities and sensorimotor coordination) was assessed from the day of injection, once a week, for 9 weeks. Finally, 9 weeks postinjection, the spinal reflexivity (rate-dependent depression of the H-reflex) was measured. The results indicate that the hydrogel did not induce an additional inflammation. Furthermore, we observed the same significant locomotor improvements in hydrogel-injected animals as in trained saline-injected animals. However, the combination of hydrogel with exercise did not show higher recovery compared to that evaluated by the two strategies independently. Finally, the H-reflex depression recovery was found to be induced by the hydrogel and, albeit to a lesser degree, exercise. However, no recovery was observed when the two strategies were combined. Our results highlight the effectiveness of our copolymer and its high therapeutic potential to preserve/repair the spinal cord after lesion.

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Section: Discussionsupporting

confidence: 82%

Delayed Injection of a Physically Cross-Linked PNIPAAm-g-PEG Hydrogel in Rat Contused Spinal Cord Improves Functional Recovery

et al. 2020

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“…In a study that combined bipedal and quadrupedal TMT with anti-Nogo-A treatment, no synergistic effects were observed [ 66 ]. The combinations of dopaminergic treatment and passive motorized bicycles, fluoxetine and TMT, and cyproheptadine and TMT did not show any collaborative effect on spasticity, as assessed by behavior and electrophysiological evaluation [ 38 , 40 ]. In addition, although every single treatment with DD-AVP medication and TMT showed a beneficial effect on urination, their combinatorial treatment did not have any additive effect [ 76 ].…”

Section: Discussionmentioning

confidence: 99%

“…In a similar intervention, Liu et al applied carbidopa, a decarboxylase inhibitor, and L-DOPA, i.e., a noradrenergic/dopaminergic precursor, together with passive bike exercise. They showed that exercise, medication, and combinatorial treatment each had comparable effects in suppressing spasticity in an electrophysiological evaluation [40]. (2) Addition of TMT effectively induced downregulation of 5-HT 2A receptor in combination groups as well as control.…”

Section: Commercially Available Serotonin Agonistsmentioning

confidence: 99%

Do Pharmacological Treatments Act in Collaboration with Rehabilitation in Spinal Cord Injury Treatment? A Review of Preclinical Studies

Tashiro,

Shibata,

Nagoshi

et al. 2024

Cells

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There is no choice other than rehabilitation as a practical medical treatment to restore impairments or improve activities after acute treatment in people with spinal cord injury (SCI); however, the effect is unremarkable. Therefore, researchers have been seeking effective pharmacological treatments. These will, hopefully, exert a greater effect when combined with rehabilitation. However, no review has specifically summarized the combinatorial effects of rehabilitation with various medical agents. In the current review, which included 43 articles, we summarized the combinatorial effects according to the properties of the medical agents, namely neuromodulation, neurotrophic factors, counteraction to inhibitory factors, and others. The recovery processes promoted by rehabilitation include the regeneration of tracts, neuroprotection, scar tissue reorganization, plasticity of spinal circuits, microenvironmental change in the spinal cord, and enforcement of the musculoskeletal system, which are additive, complementary, or even synergistic with medication in many cases. However, there are some cases that lack interaction or even demonstrate competition between medication and rehabilitation. A large fraction of the combinatorial mechanisms remains to be elucidated, and very few studies have investigated complex combinations of these agents or targeted chronically injured spinal cords.

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“…Exercise is also involved in the nervous system gene regulation, associated to apoptosis and cellular growth signaling pathways (PTEN, PDCD4, RAS mRNA and Bcl-2/Bax). This can produce axonal growth and reconnection improving injured SC morphology [57,58].…”

Section: Combination Of Exercise and Therapeutic Strategiesmentioning

confidence: 99%

The Role of Supraspinal Structures for Recovery after SCI: From Motor Dysfunction to Mental Health

Torre-Valdovinos¹,

Osuna-Carrasco²,

Ramos³

2021

Paraplegia

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Neural circuitry controlling limbed locomotion is located in the spinal cord, known as Central Pattern Generators (CPGs). After a traumatic Spinal Cord Injury (SCI), ascending and descending tracts are damaged, interrupting the communication between CPGs and supraspinal structures that are fundamental to initiate, control and adapt movement to the environment. Although low vertebrates and some mammals regain some physiological functions after a spinal insult, the capacity to recover in hominids is rather limited. The consequences after SCI include physiological (sensory, autonomic and motor) and mental dysfunctions, which causes a profound impact in social and economic aspects of patients and their relatives Despite the recent progress in the development of therapeutic strategies for SCI, there is no satisfactory agreement for choosing the best treatment that restores the affected functions of people suffering the devastating consequences after SCI. Studies have described that patients with chronic SCI can achieve some degree of neurorestoration with strategies that include physical rehabilitation, neuroprosthesis, electrical stimulation or cell therapies. Particularly in the human, the contribution of supraspinal structures to the clinical manifestations of gait deficits in people with SCI and its potential role as therapeutic targets is not well known. Additionally, mental health is considered fundamental as it represents the first step to overcome daily adversities and to face progression of this unfortunate condition. This chapter focuses on the consequences of spinal cord disconnection from supraspinal structures, from motor dysfunction to mental health. Recent advancements on the study of supraspinal structures and combination of different approaches to promote recovery after SCI are discussed. Promising strategies are used alone or in combination and include drugs, physical exercise, robotic devices, and electrical stimulation.

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l-Dopa effect on frequency-dependent depression of the H-reflex in adult rats with complete spinal cord transection

Cited by 15 publications

References 44 publications

Delayed Injection of a Physically Cross-Linked PNIPAAm-g-PEG Hydrogel in Rat Contused Spinal Cord Improves Functional Recovery

Delayed Injection of a Physically Cross-Linked PNIPAAm-g-PEG Hydrogel in Rat Contused Spinal Cord Improves Functional Recovery

Do Pharmacological Treatments Act in Collaboration with Rehabilitation in Spinal Cord Injury Treatment? A Review of Preclinical Studies

The Role of Supraspinal Structures for Recovery after SCI: From Motor Dysfunction to Mental Health

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