scholarly journals Newly regenerated axons via scaffolds promote sub-lesional reorganization and motor recovery with epidural electrical stimulation

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Ahad M. Siddiqui ◽  
Riazul Islam ◽  
Carlos A. Cuellar ◽  
Jodi L. Silvernail ◽  
Bruce Knudsen ◽  
...  

AbstractHere, we report the effect of newly regenerated axons via scaffolds on reorganization of spinal circuitry and restoration of motor functions with epidural electrical stimulation (EES). Motor recovery was evaluated for 7 weeks after spinal transection and following implantation with scaffolds seeded with neurotrophin producing Schwann cell and with rapamycin microspheres. Combined treatment with scaffolds and EES-enabled stepping led to functional improvement compared to groups with scaffold or EES, although, the number of axons across scaffolds was not different between groups. Re-transection through the scaffold at week 6 reduced EES-enabled stepping, still demonstrating better performance compared to the other groups. Greater synaptic reorganization in the presence of regenerated axons was found in group with combined therapy. These findings suggest that newly regenerated axons through cell-containing scaffolds with EES-enabled motor training reorganize the sub-lesional circuitry improving motor recovery, demonstrating that neuroregenerative and neuromodulatory therapies cumulatively enhancing motor function after complete SCI.

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Li-Ling Hope Pan ◽  
Wen-Wen Yang ◽  
Chung-Lan Kao ◽  
Mei-Wun Tsai ◽  
Shun-Hwa Wei ◽  
...  

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Cheryl Carrico ◽  
KC Chelette ◽  
Laurie Nichols ◽  
Lumy Sawaki

Research has shown that peripheral nerve stimulation (PNS) can enhance motor learning following cortical lesions. Studies have also shown that intensive upper extremity motor training can significantly enhance post-stroke motor performance. Constraint-induced therapy (CIT) is a form of intensive training that restricts use of the non-paretic upper extremity during repetitive, task-oriented motor training of the paretic extremity. Extensive evidence has validated the effectiveness of CIT for enhancing post-stroke upper extremity motor recovery. No studies have evaluated how PNS may modulate the effects of CIT. Therefore, we conducted a pilot study of PNS paired with CIT and hypothesized that in subjects with stroke, pairing CIT with active PNS would lead to significantly more improved motor function in the paretic upper extremity than CIT paired with sham PNS. Outcome measures included the Fugl-Meyer Assessment Scale (FMA; primary outcome measure), the Wolf Motor Function Test (WMFT), and the Action Research Arm Test (ARAT). Nineteen chronic stroke subjects with mild to moderate upper extremity motor deficit received 2 hours of either active (n=10) or sham (n=9) PNS preceding 4 hours of CIT for 10 consecutive weekdays. Changes in FMA, WMFT, and ARAT were analyzed using factorial ANOVA. Results showed significant (p<0.05) change in all measures at completion evaluation compared with baseline (FMA (p=0.005); WMFT (p=0.030); ARAT (p=0.020)) as well as 1-month follow-up compared with baseline (FMA (p=0.048); WMFT (p=0.045); ARAT (p=0.047)). These results highlight the enormous potential for PNS paired with CIT to enhance post-stroke upper extremity motor recovery more effectively than CIT alone.


2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Michiko Arima ◽  
Atsuko Ogata ◽  
Kazumi Kawahira ◽  
Megumi Shimodozono

The grasp reflex is a distressing symptom but the need to treat or suppress it has rarely been discussed in the literature. We report the case of a 17-year-old man who had suffered cerebral infarction of the right putamen and temporal lobe 10 years previously. Forced grasping of the hemiparetic left upper limb was improved after a unique combined treatment. Botulinum toxin type A (BTX-A) was first injected into the left biceps, wrist flexor muscles, and finger flexor muscles. Forced grasping was reduced along with spasticity of the upper limb. In addition, repetitive facilitative exercise and object-related training were performed under low-amplitude continuous neuromuscular electrical stimulation. Since this 2-week treatment improved upper limb function, we compared brain activities, as measured by near-infrared spectroscopy during finger pinching, before and after the combined treatment. Brain activities in the ipsilesional sensorimotor cortex (SMC) and medial frontal cortex (MFC) during pinching under electrical stimulation after treatment were greater than those before. The results suggest that training under electrical stimulation after BTX-A treatment may modulate the activities of the ipsilesional SMC and MFC and lead to functional improvement of the affected upper limb with forced grasping.


2012 ◽  
Vol 56 (6) ◽  
pp. 2858-2867 ◽  
Author(s):  
Sydnei M. da Silva ◽  
Izabela F. G. Amorim ◽  
Raul R. Ribeiro ◽  
Erly G. Azevedo ◽  
Cynthia Demicheli ◽  
...  

ABSTRACTAn innovative liposomal formulation of meglumine antimoniate (LMA) was recently reported to promote both long-term parasite suppression and reduction of infectivity to sand flies in dogs with visceral leishmaniasis. However, 5 months after treatment, parasites were still found in the bone marrow of all treated dogs. In order to improve treatment with LMA, the present study aimed to evaluate its efficacy in combination with allopurinol. Mongrel dogs naturally infected withLeishmania infantumwere treated with six doses of LMA (6.5 mg Sb/kg of body weight/dose) given at 4-day intervals, plus allopurinol (20 mg/kg/24 hper os) for 140 days. Comparison was made with groups treated with LMA, allopurinol, empty liposomes plus allopurinol, empty liposomes, and saline. Dogs remained without treatment from day 140 to 200 after the start of treatment. The drug combination promoted both clinical improvement of dogs and significant reduction in the parasitic load in bone marrow and spleen on days 140 and 200 compared to these parameters in the pretreatment period. This is in contrast with the other protocols, which did not result in significant reduction of the bone marrow parasite load on day 200. Strikingly, the combined treatment, in contrast to the other regimens, induced negative quantitative PCR (qPCR) results in the liver of 100% of the dogs. Both xenodiagnosis and skin parasite determination by qPCR indicated that the drug combination was effective in blocking the transmission of skin parasites to sand flies. Based on all of the parasitological tests performed on day 200, 50% of the animals that received the combined treatment were considered cured.


2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Brian A. Karamian ◽  
Nicholas Siegel ◽  
Blake Nourie ◽  
Mijail D. Serruya ◽  
Robert F. Heary ◽  
...  

AbstractElectrical stimulation is used to elicit muscle contraction and can be utilized for neurorehabilitation following spinal cord injury when paired with voluntary motor training. This technology is now an important therapeutic intervention that results in improvement in motor function in patients with spinal cord injuries. The purpose of this review is to summarize the various forms of electrical stimulation technology that exist and their applications. Furthermore, this paper addresses the potential future of the technology.


2021 ◽  
Vol 2 (1) ◽  
pp. 11-13
Author(s):  
I. N. Totrov ◽  
S. A. Ambalova ◽  
A. M. Kupeeva ◽  
Z. A. Albegova

Aim. To study the effectiveness of combined treatment of osteoarthritis (OA) using tereklit clay in the Republic of North Ossetia-Alania.Material and methods. The study included 110 patients aged 34 to 65 years with a disease duration of 1 to 10 years or more, in whom OA was diagnosed as polyosteoarthritis of I, II, III stages. All patients underwent clinical, X-ray and laboratory research, as well as osteodensitometry. In the conditions of the rehabilitation center in Vladikavkaz, patients were prescribed segmental reflex applications of tereklit clay on the affected joints at a temperature of 42 C for 15 minutes for 2 days in a row, followed by a day of rest. The course lasted 10 procedures.Results. As a result, favorable changes were observed, manifested in a decrease in pain and swelling in the joints, as well as in an improvement in its motor function on days 7-10 of treatment. The balneal reaction was not observed in any case.Conclusion. Tereklit clay applications are effective within combined therapy of patients with OA. Contraindication to clay therapy is OA with reactive synovitis, severe pain and exudation.


1968 ◽  
Vol 57 (4) ◽  
pp. 565-577 ◽  
Author(s):  
K. E. Røkke ◽  
J. H. Vogt

ABSTRACT A report is given on 95 thyrotoxic patients treated with a combination of 400 mg propylthiouracil and 400 mg of potassium perchlorate. Perchlorate was stopped when a marked remission of symptoms was obtained, on an average after less than 7 weeks. Euthyroidism was found on an average after 7.2 weeks. The basal metabolic rate, PBI, plasma total cholesterol and weight showed a fairly rapid normalization. Thirteen of the 95 patients were given radio-iodine therapy shortly before drug therapy was started. The remaining 82 cases were grouped together with the 23 cases previously reported. Of the total of 105 cases, 96 became euthyroid on combined therapy. For the frequency of side-effects, the thirteen cases mentioned above were included, giving a total of 118 cases. Eight cases showed an increase in goitre size and 15 cases had other side-effects, of which three were granulocytopenia due to propylthiouracil. The possibility of a higher frequency of mainly minor side-effects on combined therapy has to be balanced against the seemingly rapid and reliable therapeutic effect. Combined treatment, perhaps with even smaller doses than reported here, can be recommended in selected cases of thyrotoxicosis where a shortening of the thyrotoxic state seems of importance, or possibly where difficulties due to iodine exposure may be anticipated, provided adequate control measures are taken.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Helena de Castro e Gloria ◽  
Laura Jesuíno Nogueira ◽  
Patrícia Bencke Grudzinski ◽  
Paola Victória da Costa Ghignatti ◽  
Temenouga Nikolova Guecheva ◽  
...  

Abstract Background The advances in colorectal cancer (CRC) treatment include the identification of deficiencies in Mismatch Repair (MMR) pathway to predict the benefit of adjuvant 5-fluorouracil (5-FU) and oxaliplatin for stage II CRC and immunotherapy. Defective MMR contributes to chemoresistance in CRC. A growing body of evidence supports the role of Poly-(ADP-ribose) polymerase (PARP) inhibitors, such as Olaparib, in the treatment of different subsets of cancer beyond the tumors with homologous recombination deficiencies. In this work we evaluated the effect of Olaparib on 5-FU cytotoxicity in MMR-deficient and proficient CRC cells and the mechanisms involved. Methods Human colon cancer cell lines, proficient (HT29) and deficient (HCT116) in MMR, were treated with 5-FU and Olaparib. Cytotoxicity was assessed by MTT and clonogenic assays, apoptosis induction and cell cycle progression by flow cytometry, DNA damage by comet assay. Adhesion and transwell migration assays were also performed. Results Our results showed enhancement of the 5-FU citotoxicity by Olaparib in MMR-deficient HCT116 colon cancer cells. Moreover, the combined treatment with Olaparib and 5-FU induced G2/M arrest, apoptosis and polyploidy in these cells. In MMR proficient HT29 cells, the Olaparib alone reduced clonogenic survival, induced DNA damage accumulation and decreased the adhesion and migration capacities. Conclusion Our results suggest benefits of Olaparib inclusion in CRC treatment, as combination with 5-FU for MMR deficient CRC and as monotherapy for MMR proficient CRC. Thus, combined therapy with Olaparib could be a strategy to overcome 5-FU chemotherapeutic resistance in MMR-deficient CRC.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chris Donnelly ◽  
Jonathan Stegmüller ◽  
Anthony J. Blazevich ◽  
Fabienne Crettaz von Roten ◽  
Bengt Kayser ◽  
...  

AbstractThe effectiveness of neuromuscular electrical stimulation (NMES) for rehabilitation is proportional to the evoked torque. The progressive increase in torque (extra torque) that may develop in response to low intensity wide-pulse high-frequency (WPHF) NMES holds great promise for rehabilitation as it overcomes the main limitation of NMES, namely discomfort. WPHF NMES extra torque is thought to result from reflexively recruited motor units at the spinal level. However, whether WPHF NMES evoked force can be modulated is unknown. Therefore, we examined the effect of two interventions known to change the state of spinal circuitry in opposite ways on evoked torque and motor unit recruitment by WPHF NMES. The interventions were high-frequency transcutaneous electrical nerve stimulation (TENS) and anodal transcutaneous spinal direct current stimulation (tsDCS). We show that TENS performed before a bout of WPHF NMES results in lower evoked torque (median change in torque time-integral: − 56%) indicating that WPHF NMES-evoked torque might be modulated. In contrast, the anodal tsDCS protocol used had no effect on any measured parameter. Our results demonstrate that WPHF NMES extra torque can be modulated and although the TENS intervention blunted extra torque production, the finding that central contribution to WPHF NMES-evoked torques can be modulated opens new avenues for designing interventions to enhance WPHF NMES.


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