Functional recovery in spinal cord injured rats using polypyrrole/iodine implants and treadmill training

Abstract

Currently, there is no universally accepted treatment for traumatic spinal cord injury (TSCI), a pathology that can cause paraplegia or quadriplegia. Due to the complexity of TSCI, more than one therapeutic strategy may be necessary to regain lost functions. Therefore, the present study proposes the use of implants of mesoparticles (MPs) of polypyrrole/iodine (PPy/I) synthesized by plasma for neuroprotection promotion and functional recovery in combination with treadmill training (TT) for neuroplasticity promotion and maintenance of muscle tone. PPy/I films were synthesized by plasma and pulverized to obtain MPs. Rats with a TSCI produced by the NYU impactor were divided into four groups: Vehicle (saline solution); MPs (PPy/I implant); Vehicle-TT (saline solution + TT); and MPs-TT (PPy/I implant + TT). The vehicle or MPs (30 μL) were injected into the lesion site 48 h after a TSCI. Four days later, TT was carried out 5 days a week for 2 months. Functional recovery was evaluated weekly using the BBB motor scale for 9 weeks and tissue protection using histological and morphometric analysis thereafter. Although the MPs of PPy/I increased nerve tissue preservation (P = 0.03) and promoted functional recovery (P = 0.015), combination with TT did not produce better neuroprotection, but significantly improved functional results (P = 0.000) when comparing with the vehicle group. So, use these therapeutic strategies by separately could stimulate specific mechanisms of neuroprotection and neuroregeneration, but when using together they could mainly potentiate different mechanisms of neuronal plasticity in the preserved spinal cord tissue after a TSCI and produce a significant functional recovery. The implant of mesoparticles of polypyrrole/iodine into the injured spinal cord displayed good integration into the nervous tissue without a response of rejection, as well as an increased in the amount of preserved tissue and a better functional recovery than the group without transplant after a traumatic spinal cord injury by contusion in rats. The relevance of the present results is that polypyrrole/iodine implants were synthesized by plasma instead by conventional chemical or electrochemical methods. Synthesis by plasma modifies physicochemical properties of polypyrrole/iodine implants, which can be responsible of the histological response and functional results. Furthermore, no additional molecules or trophic factors or cells were added to the implant for obtain such results. Even more, when the implant was used together with physical rehabilitation, better functional recovery was obtained than that observed when these strategies were used by separately.

Exercise Training Promotes Functional Recovery after Spinal Cord Injury

“…The implantation of polypyrrole/iodine (PPy/I) can protect nerve tissue and promote functional recovery [75]. If combined with treadmill exercise training, this effect is more significant [2]. Alluin et al showed that combination therapy of chondroitinase ABC, neurotrophic factors, and exercise training not only enhanced active motor function recovery by enhancing neuroanatomical plasticity of the descending tracts (corticospinal tract and 5-HT pathway) but also significantly reduced the astrocyte proliferation and inflammation around lesions [76].…”

“…In USA, about 250,000 people suffer from varying degrees of SCI each year, with an annual rate of up to 28–50/million. Currently, there is a lack of effective clinical therapy to restore nerve function after SCI [2, 3]. Instead, exercise has become the most important quantifiable means for functional recovery [4, 5], and its mechanism has been studied by both clinical doctors and basic researchers.…”

Chemical States of Plasma Polypyrrole Coatings on Stainless Steel Stents

“…Nitinol and stainless steel (SS) are metal alloys usually used to construct stents, however, they have different chemical reactivity and retain differently the coatings on. Materials as metal, paper or fabric have been covered with Polypyrrole (PPy) to be used in biomedical applications, sensing devices, conducting fabrics and papers, among others . Plasma polypyrroles doped with iodine have shown affinity to solutions of salt concentration similar to human tissues with high possibilities to interact with cell tissues .…”

“…PPy has proven good biocompatibility with several human tissues, spinal cord tissues among them . In this work, stainless steel stents were covered with PPy synthesized by plasma, and the chemical states of the coating were studied at different distance from the surface to know the chemical composition to face a possible fluid erosion.…”

Polymeric implant of methylprednisolone for spinal injury: preparation and characterization

“…Many potent nonsteroidal antiinflammatory drugs (NSAIDs) and steroids (in high dosage) are administered for the same. But to provide the prolonged and target specific drug delivery various NSAIDs and steroids have been investigated for intrathecal administration so as to provide improved therapeutic effect [8,9]. Various biodegradable polymers have been investigated for preparing scaffolds or polymeric network/platform/implant of developing for neuroprotective and neuroregenerative drug delivery systems in spinal cord injuries [10,11].…”