Novel neuroprotective tetramethylpyrazine analog T-006 promotes neurogenesis and neurological restoration in a rat model of stroke

So which of the 5 causes of the neuronal cascade of death in the first week is this addressing? Stop using neuroprotection, it doesn't connotate ANY SENSE OF URGENCY. If you don't know what you were addressing you were just flailing in the dark and got lucky. That is not a way to run stroke research. You follow and solve the stroke strategy of which we have none. 

Novel neuroprotective tetramethylpyrazine analog T-006 promotes neurogenesis and neurological restoration in a rat model of stroke

Wu, Liangmiao^a,*; Cao, Jie^a,*; Li, Ning^a; Chen, Haiyun^a; Liu, Wei^b; Zhang, Gaoxiao^a; Liu, Yu^c; Wang, Yuqiang^a; Sun, Yewei^a; Zhang, Zaijun^a

NeuroReport: April 08, 2019 - Volume Publish Ahead of Print - Issue - p

doi: 10.1097/WNR.0000000000001256

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• Abstract
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Neuronal death is among the deleterious pathological changes that occur after cerebral ischemia and can lead to transient or permanent neurological deficits. The tetramethylpyrazine analog T-006 has been shown to be a multifunctional neuroprotective agent; however, its neuroprotective effect and mechanism of action have not been studied in ischemic stroke model rats. This study investigated the neuroprotective effects of T-006 in rat stroke model using a battery of behavioral and molecular biological tests. Results indicated that T-006 treatment significantly improved neurological function and behavior. Double immunofluorescence staining showed that T-006 visibly improved the number of NeuN⁺/BrdU⁺, Nestin⁺/BrdU⁺, and DCX⁺/BrdU⁺ cells and induced neuronal regeneration. Western blot analyses indicated that T-006 upregulated neurogenesis-related protein expression of postsynaptic density protein 95, brain-derived neurotrophic factor, synaptophysin, and myelin basic protein. Collectively, these data suggest that T-006 stimulated neurogenesis in rats with middle cerebral artery occlusion and restored neurological functions.

© 2019 Wolters Kluwer Health | Lippincott Williams & Wilkins

1,026 failed Experimental treatments in acute stroke

This just proves that we have no stroke leadership. Leaders do not give up when presented with failures.  We will never get any urgency as long as we still call it neuroprotection rather than the neuronal cascade of death. Which term suggests urgency to lay people? 13 years and still no followup? Incompetence at the highest levels.

1,026 Experimental treatments in acute stroke

Victoria E. O'Collins B.Sci

Malcolm R. Macleod MRCP, PhD

Geoffrey A. Donnan MD, FRACP

Laura L. Horky MD, PhD

Bart H. van der Worp MD, PhD

David W. Howells PhD

First published: 17 February 2006

https://doi.org/10.1002/ana.20741

Cited by: 687

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Abstract

Objective

Preclinical evaluation of neuroprotectants fostered high expectations of clinical efficacy. When not matched, the question arises whether experiments are poor indicators of clinical outcome or whether the best drugs were not taken forward to clinical trial. Therefore, we endeavored to contrast experimental efficacy and scope of testing of drugs used clinically and those tested only experimentally.

Methods

We identified neuroprotectants and reports of experimental efficacy via a systematic search. Controlled in vivo and in vitro experiments using functional or histological end points were selected for analysis. Relationships between outcome, drug mechanism, scope of testing, and clinical trial status were assessed statistically.

Results

There was no evidence that drugs used clinically (114 drugs) were more effective experimentally than those tested only in animal models (912 drugs), for example, improvement in focal models averaged 31.3 ± 16.7% versus 24.4 ± 32.9%, p > 0.05, respectively. Scope of testing using Stroke Therapy Academic Industry Roundtable (STAIR) criteria was highly variable, and no relationship was found between mechanism and efficacy.

Interpretation

The results question whether the most efficacious drugs are being selected for stroke clinical trials. This may partially explain the slow progress in developing treatments. Greater rigor in the conduct, reporting, and analysis of animal data will improve the transition of scientific advances from bench to bedside. Ann Neurol 2006

Mirror therapy for improving motor function after stroke

With 44 posts on mirror therapy back to Oct. 2012 this review still suggests further research. Fuck, do you think stroke survivors have forever to wait for a protocol? Write one up now and update as new research comes in. My god, we need stroke survivors in charge, they would have a sense of urgency.

http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD008449.pub3/full?platform=hootsuite

Authors

• 
  

  Corresponding author
  

  1. Erste Europäische Schule für Physiotherapie, Ergotherapie und Logopädie, Klinik Bavaria Kreischa, Kreischa, Sachsen, Germany
  2. Martin Luther University Halle-Wittenberg, Institute for Health and Nursing Science, German Center for Evidence-based Nursing, Halle/Saale, Germany
  3. Fakultät Soziale Arbeit und Gesundheit, HAWK Hochschule für angewandte Wissenschaft und Kunst, Hildesheim, Germany

  • Holm Thieme, Schule für Physiotherapie, Erste Europäische Schule für Physiotherapie, Ergotherapie und Logopädie, Klinik BAVARIA Kreischa, Dresdner Str. 12, Kreischa, Sachsen, 01731, Germany. holm.thieme@physiotherapie-schule-kreischa.de.

• 
  

  1. Charité - University Medicine Berlin, Center for Stroke Research Berlin, Berlin, Germany
  2. MEDIAN Klinik Berlin-Kladow, Berlin, Germany

• 
  

  1. Technical University Dresden, Department of Public Health, Dresden Medical School, Dresden, Germany

• 
  

  1. Helios Klinik Schloss Pulsnitz, Neurological Rehabilitation, Pulsnitz, Saxony, Germany

• 
  

  1. Martin Luther University Halle-Wittenberg, Institute for Health and Nursing Science, German Center for Evidence-based Nursing, Halle/Saale, Germany

• 
  

  1. Fakultät Soziale Arbeit und Gesundheit, HAWK Hochschule für angewandte Wissenschaft und Kunst, Hildesheim, Germany

• 
  

  1. Charité - University Medicine Berlin, Center for Stroke Research Berlin, Berlin, Germany
  2. MEDIAN Klinik Berlin-Kladow, Berlin, Germany

• First published: 11 July 2018
• Editorial Group: Cochrane Stroke Group
• DOI: 10.1002/14651858.CD008449.pub3  View/save citation
• Cited by (CrossRef): 0 articles Check for updates

Abstract

Background

Mirror therapy is used to improve motor function after stroke. During mirror therapy, a mirror is placed in the person's midsagittal plane, thus reflecting movements of the non-paretic side as if it were the affected side.

Objectives

To summarise the effectiveness of mirror therapy compared with no treatment, placebo or sham therapy, or other treatments for improving motor function and motor impairment after stroke. We also aimed to assess the effects of mirror therapy on activities of daily living, pain, and visuospatial neglect.

Search methods

We searched the Cochrane Stroke Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, AMED, PsycINFO and PEDro (last searched 16 August 2017). We also handsearched relevant conference proceedings, trials and research registers, checked reference lists, and contacted trialists, researchers and experts in our field of study.

Selection criteria

We included randomised controlled trials (RCTs) and randomised cross-over trials comparing mirror therapy with any control intervention for people after stroke.

Data collection and analysis

Two review authors independently selected trials based on the inclusion criteria, documented the methodological quality, assessed risks of bias in the included studies, and extracted data. We assessed the quality of the evidence using the GRADE approach. We analysed the results as standardised mean differences (SMDs) or mean differences (MDs) for continuous variables, and as odds ratios (ORs) for dichotomous variables.

Main results

We included 62 studies with a total of 1982 participants that compared mirror therapy with other interventions. Of these, 57 were randomised controlled trials and five randomised cross-over trials. Participants had a mean age of 59 years (30 to 73 years). Mirror therapy was provided three to seven times a week, between 15 and 60 minutes for each session for two to eight weeks (on average five times a week, 30 minutes a session for four weeks).When compared with all other interventions, we found moderate-quality evidence that mirror therapy has a significant positive effect on motor function (SMD 0.47, 95% CI 0.27 to 0.67; 1173 participants; 36 studies) and motor impairment (SMD 0.49, 95% CI 0.32 to 0.66; 1292 participants; 39 studies). However, effects on motor function are influenced by the type of control intervention. Additionally, based on moderate-quality evidence, mirror therapy may improve activities of daily living (SMD 0.48, 95% CI 0.30 to 0.65; 622 participants; 19 studies). We found low-quality evidence for a significant positive effect on pain (SMD −0.89, 95% CI −1.67 to −0.11; 248 participants; 6 studies) and no clear effect for improving visuospatial neglect (SMD 1.06, 95% CI −0.10 to 2.23; 175 participants; 5 studies). No adverse effects were reported.

Authors' conclusions

The results indicate evidence for the effectiveness of mirror therapy for improving upper extremity motor function, motor impairment, activities of daily living, and pain, at least as an adjunct to conventional rehabilitation for people after stroke. Major limitations are small sample sizes and lack of reporting of methodological details, resulting in uncertain evidence quality.

Plain language summary

Mirror therapy for improving movement after stroke

Review question
Does mirror therapy improve movement, the performance of daily activities, pain, and lack of attention to and awareness of the affected field of vision (visuospatial neglect) after stroke.

Backround
Paralysis of the arm or leg is common after stroke and frequently causes problems with activities of daily living such as walking, dressing, or eating. Mirror therapy (MT) is a rehabilitation therapy in which a mirror is placed between the arms or legs so that the image of a moving non-affected limb gives the illusion of normal movement in the affected limb. By this setup, different brain regions for movement, sensation, and pain are stimulated. However, the precise working mechanisms of mirror therapy are still unclear. We conducted a search for literature in various databases and extracted the data of relevant studies.

Search date
This review identified studies up to 16 August 2017.

Study characteristics
We found 62 relevant studies, of which 57 randomly allocated participants to receive either MT or a control therapy (randomised controlled trials) and five provided both therapies to all participants, but in random order (cross-over trials). The studies involved a total of 1982 participants with a mean age of 59 years (30 to 73 years) after stroke. Mirror therapy was provided three to seven times a week, between 15 and 60 minutes for each session for two to eight weeks (on average five times a week, 30 minutes a session for four weeks).

Key results
At the end of treatment, mirror therapy moderately improved movement of the affected upper and lower limb and the ability to carry out daily activities for people within and also beyond six months after the stroke. Mirror therapy reduced pain after stroke, but mainly in people with a complex regional pain syndrome. We found no clear effect for visuospatial neglect. The beneficial effects on movement were maintained for six months, but not in all study groups. No adverse effects were reported.

Quality of the evidence
The studies provide moderately-reliable evidence that MT improves movement (motor function, motor impairment) and the performance of daily activities. However, there was only low reliability that MT decreases pain and visuospatial neglect. This may be due to the small number of studies. Further research is needed, with larger methodologically-sound studies.