PDF herunterladen
CC BY-NC-ND 4.0 · Ann Natl Acad Med Sci 2019; 55(03): 124-131
DOI: 10.1055/s-0039-1698495
Review Article
National Academy of Medical Sciences (India)

Restorative Therapies after Stroke: Drugs, Devices, and Robotics

M. V. Padma Srivastava
1   Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
,
Neha Kuthiala
1   Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
05. Dezember 2019 (online)

   Lizenzen und Reprints

Abstract

Restorative therapies aim to improve outcome by salvaging threatened brain, as with reperfusion or neuroprotective drugs and also by promoting plasticity within surviving neural tissue. Restorative therapies typically have a therapeutic time window measured in days and weeks and so have the potential to be assessed by a large fraction of patients with a new stroke. Examples of such brain repair therapies include growth factors, cell-based therapies, and devices. Positive clinical trials have been reported in human studies for several classes of restorative therapy after stroke. These include robotics, constrain-induced movement therapy (CIMT), and pharmacological therapy, such as levodopa and selective serotonin reuptake inhibitors. In addition, several forms of noninvasive cortical stimulation, such as rapid transcranial magnetic stimulation, transcranial direct current stimulation, and theta-burst stimulation, have shown promise in early phase studies. The current review gives a glimpse of the existing strategies, those on the anvil of implementation and those with a hope of launch in near future.

Keywords

stroke - stem cell therapy - vascular endothelial growth factor - physiotherapy
 

  • References

  • 1 Deb P, Sharma S, Hassan KM. Pathophysiologic mechanisms of acute ischemic stroke: An overview with emphasis on therapeutic significance beyond thrombolysis. Pathophysiology 2010; 17 (03) 197-218
    CrossrefPubMedGoogle Scholar
  • 2 Cramer SC, Cassidy JM. Application of fMRI to monitor motor rehabilitation. In: Filippi M. ed. fMRI Techniques and Protocols. New York, NY: Humana Press; 2016: 833-849
    Google Scholar
  • 3 Cramer SC. The EXCITE trial: a major step forward for restorative therapies in stroke. Stroke 2007; 38 (07) 2204-2205
    CrossrefPubMedGoogle Scholar
  • 4 Cramer SC. Treatments to promote neural repair after stroke. J. Stroke 2018; 20 (01) 57-70
    Google Scholar
  • 5 Srivastava MVP. Restorative therapies after stroke: drugs, devices and robotics. Ann Natl Acad Med Sci 2017; 53 (01) 51-65
    Google Scholar
  • 6 Srivastava MVP, Bhasin A, Talwar T, Moonis M. Pharmacological agents in post stroke recovery. J Neurol Stroke 2014; 1 (06) 00040
    Google Scholar
  • 7 Wahl AS, Schwab ME. Finding an optimal rehabilitation paradigm after stroke: enhancing fiber growth and training of the brain at the right moment. Front Hum Neurosci 2014; 8 (381) 381
    PubMedGoogle Scholar
  • 8 Rogalewski A, Schneider A, Ringelstein EB, Schäbitz WR. Toward a multimodal neuroprotective treatment of stroke. Stroke 2006; 37 (04) 1129-1136
    CrossrefPubMedGoogle Scholar
  • 9 Belayev L. Overcoming barriers to translation from experimental stroke models. In: Lapchak PA, Zhang JH. eds. Translational Stroke Research. Ney York, NY: Springer; 2012: 471-492
    CrossrefGoogle Scholar
  • 10 Padma V, Fisher M, Moonis M. Thrombolytic therapy for acute ischemic stroke: 3 h and beyond. Expert Rev Neurother 2005; 5 (02) 223-233
    CrossrefPubMedGoogle Scholar
  • 11 Padma S, Majaz M. Intra-arterial versus intra-venous thrombolysis within and after the first 3 hours of stroke onset. Arch Med Sci 2010; 6 (03) 303-315
    PubMedGoogle Scholar
  • 12 Molina CA, Saver JL. Extending reperfusion therapy for acute ischemic stroke: emerging pharmacological, mechanical, and imaging strategies. Stroke 2005; 36 (10) 2311-2320
    CrossrefPubMedGoogle Scholar
  • 13 Abou-Chebl A. Endovascular treatment of acute ischemic stroke may be safely performed with no time window limit in appropriately selected patients. Stroke 2010; 41 (09) 1996-2000
    CrossrefPubMedGoogle Scholar
  • 14 Saver JL. Improving reperfusion therapy for acute ischaemic stroke. J Thromb Haemost 2011; 9 (01) (Suppl. 01) 333-343
    PubMedGoogle Scholar
  • 15 Berkhemer OA, Fransen PS, Beumer D. et al. MR CLEAN Investigators. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015; 372 (01) 11-20
    CrossrefPubMedGoogle Scholar
  • 16 Smith WS, Yan B. REVASCAT trial: further advancement in endovascular stroke therapy. Stroke 2015; 46 (10) 3012-3013
    CrossrefPubMedGoogle Scholar
  • 17 Padma Srivastava MV. Management of stroke: the triumphs and the travails. Neurol India 2016; 64 (Suppl. 07) S6-S7
    CrossrefPubMedGoogle Scholar
  • 18 Hill MD, Goyal M, Demchuk AM. Endovascular stroke therapy–a new era. Int J Stroke 2015; 10 (03) 278-279
    CrossrefPubMedGoogle Scholar
  • 19 Chen J, Venkat P, Zacharek A, Chopp M. Neurorestorative therapy for stroke. Front Hum Neurosci 2014; 8: 382
    PubMedGoogle Scholar
  • 20 Zhang ZG, Chopp M. Neurorestorative therapies for stroke: underlying mechanisms and translation to the clinic. Lancet Neurol 2009; 8 (05) 491-500
    CrossrefPubMedGoogle Scholar
  • 21 Padma Srivastava MV, Bhasin A. Restorative therapy in stroke. J Transplant Technol Res 2014; 4 (02) 136
    Google Scholar
  • 22 Padma Srivastava MV. Restorative therapy in stroke using stem cells. Neurol India 2009; 57 (04) 381-386
    CrossrefPubMedGoogle Scholar
  • 23 Savitz SI, Dinsmore JH, Wechsler LR, Rosenbaum DM, Caplan LR. Cell therapy for stroke. NeuroRx 2004; 1 (04) 406-414
    CrossrefPubMedGoogle Scholar
  • 24 Okano H. Stem cell biology of the central nervous system. J. Neurosci Res 2002; 69 (06) 698-707
    Google Scholar
  • 25 National Institute of Health. Stem cell basics. Available at: https://stemcells.nih.gov/info/basics/1.htm. Accessed September 10, 2019
  • 26 Zivin JA. Cell transplant therapy for stroke: hope or hype. Neurology 2000; 55 (04) 467
    CrossrefPubMedGoogle Scholar
  • 27 Savitz SI, Rosenbaum DM, Dinsmore JH, Wechsler LR, Caplan LR. Cell transplantation for stroke. Ann Neurol 2002; 52 (03) 266-275
    CrossrefPubMedGoogle Scholar
  • 28 Björklund A, Lindvall O. Cell replacement therapies for central nervous system disorders. Nat Neurosci 2000; 3 (06) 537-544
    Google Scholar
  • 29 Isacson O, Deacon T. Neural transplantation studies reveal the brain’s capacity for continuous reconstruction. Trends Neurosci 1997; 20 (10) 477-482
    CrossrefPubMedGoogle Scholar
  • 30 Bliss T, Guzman R, Daadi M, Steinberg GK. Cell transplantation therapy for stroke. Stroke 2007; 38 (Suppl. 02) 817-826
    CrossrefPubMedGoogle Scholar
  • 31 Haas S, Weidner N, Winkler J. Adult stem cell therapy in stroke. Curr Opin Neurol 2005; 18 (01) 59-64
    CrossrefPubMedGoogle Scholar
  • 32 Prasad K, Kumar A, Sahu JK. et al. Mobilization of stem cells using G-CSF for acute ischemic stroke: a randomized controlled pilot study. Stroke Res Treat 2011; 2011: 283473
    PubMedGoogle Scholar
  • 33 Srivastava MVP, Bhasin A, Mohanty S. et al. Restorative therapy using autologous bone marrow derived mononuclear cells infusion intra-arterially in patients with cerebral palsy: An open label feasibility study. Neurol Asia 2011; 16 (03) 231-239
    Google Scholar
  • 34 Bhasin A, Srivastava MV, Kumaran SS. et al. Autologous mesenchymal stem cells in chronic stroke. Cerebrovasc Dis Extra 2011; 1 (01) 93-104
    CrossrefPubMedGoogle Scholar
  • 35 Bhasin A, Srivastava M, Bhatia R, Mohanty S, Kumaran S, Bose S. Autologous intravenous mononuclear stem cell therapy in chronic ischemic stroke. J Stem Cells Regen Med 2012; 8 (03) 181-189
    PubMedGoogle Scholar
  • 36 Bhasin A, Padma Srivastava MV, Kumaran SS, Bhatia R, Mohanty S. Neural interface of mirror therapy in chronic stroke patients: a functional magnetic resonance imaging study. Neurol India 2012; 60 (06) 570-576
    CrossrefPubMedGoogle Scholar
  • 37 Nishino H, Borlongan CV. Restoration of function by neural transplantation in the ischemic brain. Prog Brain Res 2000; 127: 461-476
    PubMedGoogle Scholar
  • 38 Bogousslavsky J, Victor SJ, Salinas EO. et al. European-Australian Fiblast (Trafermin) in Acute Stroke Group. Fiblast (trafermin) in acute stroke: results of the European-Australian phase II/III safety and efficacy trial. Cerebrovasc Dis 2002; 14 (3, 4) 239-251
    CrossrefPubMedGoogle Scholar
  • 39 Talwar T, Srivastava MVP. Role of vascular endothelial growth factor and other growth factors in post-stroke recovery. Ann Indian Acad Neurol 2014; 17 (01) 1-6
    PubMedGoogle Scholar
  • 40 Ucuzian AA, Gassman AA, East AT, Greisler HP. Molecular mediators of angiogenesis. J Burn Care Res 2010; 31 (01) 158-175
    CrossrefPubMedGoogle Scholar
  • 41 Sharma H, Srivastava MVP, Bhatia R, Kumar N, Moganty R. Does vascular endothelial growth factor (VEGF) expression in combination with physiotherapy with/without repetitive transcranial magnetic stimulation (rTMS) play the role in acute stroke recovery?. Brain Stimul 2015; 8 (02) 324
    Google Scholar
  • 42 Kubis N. Non-invasive brain stimulation to enhance post-stroke recovery. Front Neural Circuits 2016; 10: 56
    PubMedGoogle Scholar
  • 43 Kuthiala N, Srivastava MVP. Is the change in serum vascular endothelial growth factor (Vegf) after high frequency rTMS in chronic stroke indicative of neuroplasticity?. Int J Stroke 2016; 11 (3S) 228
    Google Scholar
  • 44 Zhang R, Zhang L, Zhang Z. et al. A nitric oxide donor induces neurogenesis and reduces functional deficits after stroke in rats. Ann Neurol 2001; 50 (05) 602-611
    CrossrefPubMedGoogle Scholar
  • 45 Bauer V, Sotníková R. Nitric oxide–the endothelium-derived relaxing factor and its role in endothelial functions. Gen Physiol Biophys 2010; 29 (04) 319-340
    CrossrefPubMedGoogle Scholar
  • 46 Bednar MM. The role of sildenafil in the treatment of stroke. Curr Opin Investig. Drugs 2008; 9 (07) 754-759
    Google Scholar
  • 47 Zhang R, Wang Y, Zhang L. et al. Sildenafil (Viagra) induces neurogenesis and promotes functional recovery after stroke in rats. Stroke 2002; 33 (11) 2675-2680
    CrossrefPubMedGoogle Scholar
  • 48 Clarkson AN. Perisynaptic GABA receptors: the overzealous protector. Adv Pharmacol Sci 2012; 2012: 708428
    PubMedGoogle Scholar
  • 49 Padma Srivastava MV, Bhasin A, Bhatia R. et al. Efficacy of minocycline in acute ischemic stroke: a single-blinded, placebo-controlled trial. Neurol India 2012; 60 (01) 23-28
    CrossrefPubMedGoogle Scholar
  • 50 Ehrenreich H, Hasselblatt M, Dembowski C. et al. Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med 2002; 8 (08) 495-505
    CrossrefPubMedGoogle Scholar
  • 51 Schäbitz WR, Laage R, Vogt G. et al. AXIS: a trial of intravenous granulocyte colony-stimulating factor in acute ischemic stroke. Stroke 2010; 41 (11) 2545-2551
    CrossrefPubMedGoogle Scholar
  • 52 Ehrenreich H, Weissenborn K, Prange H. et al. EPO Stroke Trial Group. Recombinant human erythropoietin in the treatment of acute ischemic stroke. Stroke 2009; 40 (12) e647-e656
    PubMedGoogle Scholar
  • 53 Cui X, Chopp M, Zacharek A. et al. Niacin treatment of stroke increases synaptic plasticity and axon growth in rats. Stroke 2010; 41 (09) 2044-2049
    CrossrefPubMedGoogle Scholar
  • 54 Greener J, Enderby P, Whurr R. Pharmacological treatment for aphasia following stroke. Cochrane Database Syst Rev 2001; 00
    Google Scholar
  • 55 Rösser N, Flöel A. Pharmacological enhancement of motor recovery in subacute and chronic stroke. NeuroRehabilitation 2008; 23 (01) 95-103
    CrossrefPubMedGoogle Scholar
  • 56 Hsu WY, Cheng CH, Liao KK, Lee IH, Lin YY. Effects of repetitive transcranial magnetic stimulation on motor functions in patients with stroke: a meta-analysis. Stroke 2012; 43 (07) 1849-1857
    CrossrefPubMedGoogle Scholar
  • 57 Langhorne P, Bernhardt J, Kwakkel G. Stroke rehabilitation. Lancet 2011; 377 (9778) 1693-1702
    CrossrefPubMedGoogle Scholar
  • 58 Giacino JT, Whyte J, Bagiella E. et al. Placebo-controlled trial of amantadine for severe traumatic brain injury. N Engl J Med 2012; 366 (09) 819-826
    CrossrefPubMedGoogle Scholar
  • 59 Gu Q. Neuromodulatory transmitter systems in the cortex and their role in cortical plasticity. Neuroscience 2002; 111 (04) 815-835
    CrossrefPubMedGoogle Scholar
  • 60 Berends HI, Nijlant JM, Movig KL, Van Putten MJ, Jannink MJ, Ijzerman MJ. The clinical use of drugs influencing neurotransmitters in the brain to promote motor recovery after stroke; a Cochrane systematic review. Eur J Phys Rehabil Med 2009; 45 (04) 621-630
    PubMedGoogle Scholar
  • 61 Floel A, Hummel F, Breitenstein C, Knecht S, Cohen LG. Dopaminergic effects on encoding of a motor memory in chronic stroke. Neurology 2005; 65 (03) 472-474
    CrossrefPubMedGoogle Scholar
  • 62 Acler M, Robol E, Fiaschi A, Manganotti P. A double blind placebo RCT to investigate the effects of serotonergic modulation on brain excitability and motor recovery in stroke patients. J Neurol 2009; 256 (07) 1152-1158
    CrossrefPubMedGoogle Scholar
  • 63 Scheidtmann K, Fries W, Müller F, Koenig E. Effect of levodopa in combination with physiotherapy on functional motor recovery after stroke: a prospective, randomised, double-blind study. Lancet 2001; 358 (9284) 787-790
    CrossrefPubMedGoogle Scholar
  • 64 Bhakta BB, Hartley S, Holloway I. et al. The DARS (Dopamine Augmented Rehabilitation in Stroke) trial: protocol for a randomised controlled trial of Co-careldopa treatment in addition to routine NHS occupational and physical therapy after stroke. Trials 2014; 15: 316
    CrossrefPubMedGoogle Scholar
  • 65 Zittel S, Weiller C, Liepert J. Citalopram improves dexterity in chronic stroke patients. Neurorehabil Neural Repair 2008; 22 (03) 311-314
    CrossrefPubMedGoogle Scholar
  • 66 Pariente J, Loubinoux I, Carel C. et al. Fluoxetine modulates motor performance and cerebral activation of patients recovering from stroke. Ann Neurol 2001; 50 (06) 718-729
    CrossrefPubMedGoogle Scholar
  • 67 Chollet F, Tardy J, Albucher JF. et al. Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial. Lancet Neurol 2011; 10 (02) 123-130
    CrossrefPubMedGoogle Scholar
  • 68 Mead GE, Hsieh CF, Lee R, Kutlubaev MA, Claxton A, Hankey GJ, Hackett ML. Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery. Cochrane Database Syst Rev 2012; 11 CD009286 DOI: 10.1002/14651858.CD0.
    CrossrefGoogle Scholar
  • 69 Reis C, Akyol O, Ho WM. et al. Phase I and phase II therapies for acute ischemic stroke: an update on currently studied drugs in clinical research. BioMed Res Int 2017; 2017: 4863079
    PubMedGoogle Scholar
  • 70 Poli P, Morone G, Rosati G, Masiero S. Robotic technologies and rehabilitation: new tools for stroke patients’ therapy. BioMed Res Int 2013; 2013: 153872
    PubMedGoogle Scholar
  • 71 Frisoli A, Solazzi M, Loconsole C, Barsotti M. New generation emerging technologies for neurorehabilitation and motor assistance. Acta Myol 2016; 35 (03) 141-144
    PubMedGoogle Scholar
  • 72 Klamroth-Marganska V, Blanco J, Campen K. Three-dimensional, task-specific robot therapy of the arm after stroke: a multicentre, parallel-group randomised trial. Lancet Neurol 2014; 13 (02) 159-166
    CrossrefPubMedGoogle Scholar