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Expert Review of Neurotherapeutics Volume 16, 2016 - Issue 2
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Reviews

Promoting recovery from ischemic stroke

Antje SchmidtDepartment of Neurology, University of Münster, Münster, GermanyCorrespondence[email protected]
&
Jens MinnerupDepartment of Neurology, University of Münster, Münster, Germany
Pages 173-186 | Received 26 Oct 2015, Accepted 16 Dec 2015, Published online: 11 Jan 2016

References

  • Papers of special note have been highlighted as
  • • of interest
  • •• of considerable interest
  • Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease study 2010. Lancet. 2013;380(9859):2095–2128.
  • Roger VL,GAS, Lloyd-Jones DM, et al. Heart disease and stroke statistics–2012 update: a report from the American Heart Association. Circulation. 2012;125(1):e2–e220.
  • Adams HP, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24(1):35–41.
  • Ferro JM. Cardioembolic stroke: an update. Lancet Neurol. 2003;2(3):177–188.
  • Seet RCS, Friedman PA, Rabinstein AA. Prolonged rhythm monitoring for the detection of occult paroxysmal atrial fibrillation in ischemic stroke of unknown cause. Circulation. 2011;124(4):477–486.
  • Fisher CM. Lacunar strokes and infarcts: a review. Neurology. 1982;32(8):871–871.
  • Doyle KP, Simon RP, Stenzel-Poore MP. Mechanisms of ischemic brain damage. Neuropharmacology. 2008;55(3):310–318.
  • Deb P, Sharma S, Hassan KM. Pathophysiologic mechanisms of acute ischemic stroke: an overview with emphasis on therapeutic significance beyond thrombolysis. Pathophysiology. 2010;17(3):197–218.
  • Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359(13):1317–1329.
  • Furlan A, Higashida R, Wechsler L, et al. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. JAMA. 1999;282(21):2003–2011.
  • Fisher M, Saver JL. Future directions of acute ischaemic stroke therapy. Lancet Neurol. 2015;14(7):758–767.
  • Campbell BCV, Donnan GA, Lees KR, et al. Endovascular stent thrombectomy: the new standard of care for large vessel ischaemic stroke. Lancet Neurol. 2015;14(8):846–854.
  • Berkhemer OA, Fransen PSS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372(1):11–20.
  • Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015;372(11):1019–1030.
  • Campbell BCV, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015;372(11):1009–1018.
  • Saver JL, Goyal M, Bonafe A, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015;372(24):2285–2295.
  • Jovin TG, Chamorro A, Cobo E, et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015;372(24):2296–2306.
  • Powers WJ, Derdeyn CP, Biller J, et al. American Heart Association/American Stroke Association Focused Update of the 2013 guidelines for the early management of patients with acute ischemic stroke regarding endovascular treatment: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015;46(10):3020–3035.
  • Vahedi K, Hofmeijer J, Juettler E, et al. Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials. Lancet Neurol. 2007;6(3):215–222.
  • Jüttler E, Unterberg A, Woitzik J, et al. Hemicraniectomy in older patients with extensive middle-cerebral-artery stroke. N Engl J Med. 2014;370(12):1091–1100.
  • Stroke Unit Trialists’ Collaboration. Organised inpatient (stroke unit) care for stroke. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD000197.
  • Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45(7):2160–2236.
  • European Stroke Organisation (ESO) Executive Committee, ESO Writing Committee. Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis. 2008;25(5):457–507.
  • Hermann DM, Chopp M. Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation. Lancet Neurol. 2012;11(4):369–380.

•A comprehensive review on the mechanisms of neural recovery following stroke.

  • Zhang ZG, Chopp M. Neurorestorative therapies for stroke: underlying mechanisms and translation to the clinic. Lancet Neurol. 2009;8(5):491–500.

•A comprehensive review on the mechanisms of neural recovery following stroke.

  • Carmichael ST. Cellular and molecular mechanisms of neural repair after stroke: making waves. Ann Neurol. 2006;59(5):735–742.
  • Park KK, Liu K, Hu Y, et al. Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway. Science. 2008;322(5903):963–966.
  • Chow DK, Groszer M, Pribadi M, et al. Laminar and compartmental regulation of dendritic growth in mature cortex. Nat Neurosci. 2009;12(2):116–118.
  • Jiang Q, Zhang ZG, Ding GL, et al. MRI detects white matter reorganization after neural progenitor cell treatment of stroke. Neuroimage. 2006;32(3):1080–1089.
  • Jiang Q, Zhang ZG, Ding GL, et al. Investigation of neural progenitor cell induced angiogenesis after embolic stroke in rat using MRI. Neuroimage. 2005;28(3):698–707.
  • Alvarez-Buylla A, Garcia-Verdugo JM. Neurogenesis in adult subventricular zone. J Neurosci. 2002;22(3):629–634.
  • Doetsch F, García-Verdugo JM, Alvarez-Buylla A. Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J Neurosci. 1997;17(13):5046–5061.
  • Arvidsson A, Collin T, Kirik D, et al. Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med. 2002;8(9):963–970.
  • Zhang RL, Zhang ZG, Zhang L, et al. Proliferation and differentiation of progenitor cells in the cortex and the subventricular zone in the adult rat after focal cerebral ischemia. Neuroscience. 2001;105(1):33–41.
  • Liu XS, Zhang ZG, Zhang RL, et al. Stroke induces gene profile changes associated with neurogenesis and angiogenesis in adult subventricular zone progenitor cells. J Cereb Blood Flow Metab. 2007;27(3):564–574.
  • Hou S-W, Wang Y-Q, Xu M, et al. Functional integration of newly generated neurons into striatum after cerebral ischemia in the adult rat brain. Stroke. 2008;39(10):2837–2844.
  • Jin K, Wang X, Xie L, et al. Evidence for stroke-induced neurogenesis in the human brain. Proc Natl Acad Sci USA. 2006;103(35):13198–13202.
  • Macas J, Nern C, Plate KH, et al.Increased generation of neuronal progenitors after ischemic injury in the aged adult human forebrain. J Neurosci. 2006;26(50):13114–13119.
  • Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature. 2011;473(7347):298–307.
  • Risau W. Mechanisms of angiogenesis. Nature. 1997;386(6626):671–674.
  • Madeddu P. Therapeutic angiogenesis and vasculogenesis for tissue regeneration. Exp Physiol. 2005;90(3):315–326.
  • Quaegebeur A, Segura I, Carmeliet P. Pericytes: blood-brain barrier safeguards against neurodegeneration? Neuron. 2010;68(3):321–323.
  • Liman TG, Endres M. New vessels after stroke: postischemic neovascularization and regeneration. Cerebrovasc Dis. 2012;33(5):492–499.
  • Sun Y, Jin K, Xie L, et al. VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. J Clin Invest. 2003;111(12):1843–1851.
  • Zhang ZG, Zhang L, Jiang Q, et al. VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain. J Clin Invest. 2000;106(7):829–838.
  • Zhang ZG, Zhang L, Tsang W, et al. Correlation of VEGF and angiopoietin expression with disruption of blood-brain barrier and angiogenesis after focal cerebral ischemia. J Cereb Blood Flow Metab. 2002;22(4):379–392.
  • Heiss W-D, Kidwell CS. Imaging for prediction of functional outcome and assessment of recovery in ischemic stroke. Stroke. 2014;45(4):1195–1201.
  • Auriat AM, Neva JL, Peters S, et al. A review of transcranial magnetic stimulation and multimodal neuroimaging to characterize post-stroke neuroplasticity. Front Neurol. 2015;6:226.
  • Jang SH. A review of diffusion tensor imaging studies on motor recovery mechanisms in stroke patients. NeuroRehabilitation. 2011;28(4):345–352.
  • Lim C-M, Kim S-W, Park J-Y, et al. Fluoxetine affords robust neuroprotection in the postischemic brain via its anti-inflammatory effect. J Neurosci Res. 2009;87(4):1037–1045.
  • Li W-L, Cai H-H, Wang B, et al. Chronic fluoxetine treatment improves ischemia-induced spatial cognitive deficits through increasing hippocampal neurogenesis after stroke. J Neurosci Res. 2009;87(1):112–122.
  • Chollet F, Tardy J, Albucher J-F, et al. Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial. Lancet Neurol. 2011;10(2):123–130.

••A large clinical trial that demonstrates the translatability of neurorestorative treatments.

  • Diederich K, Frauenknecht K, Minnerup J, et al. Citicoline enhances neuroregenerative processes after experimental stroke in rats. Stroke. 2012;43(7):1931–1940.
  • Bustamante A, Giralt D, Garcia-Bonilla L, et al. Citicoline in pre-clinical animal models of stroke: a meta-analysis shows the optimal neuroprotective profile and the missing steps for jumping into a stroke clinical trial. J Neurochem. 2012;123(2):217–225.
  • Dávalos A, Alvarez-Sabín J, Castillo J, et al. Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebo-controlled study (ICTUS trial). Lancet. 2012;380(9839):349–357.
  • 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.
  • Li L, Jiang Q, Zhang L, et al. Angiogenesis and improved cerebral blood flow in the ischemic boundary area detected by MRI after administration of sildenafil to rats with embolic stroke. Brain Res. 2007;1132(1):185–192.
  • Silver B, McCarthy S, Lu M, et al. Sildenafil treatment of subacute ischemic stroke: a safety study at 25-mg daily for 2 weeks. J Stroke Cerebrovasc Dis. 2009;18(5):381–383.
  • Buchli AD, Schwab ME. Inhibition of Nogo: a key strategy to increase regeneration, plasticity and functional recovery of the lesioned central nervous system. Ann Med. 2005;37(8):556–567.

•A comprehensive review on Nogo-A inhibition.

  • Lee S-T, Chu K, Jung K-H, et al. Granulocyte colony-stimulating factor enhances angiogenesis after focal cerebral ischemia. Brain Res. 2005;1058(1–2):120–128.
  • Ringelstein EB, Thijs V, Norrving B, et al. Granulocyte colony-stimulating factor in patients with acute ischemic stroke: results of the AX200 for Ischemic Stroke trial. Stroke. 2013;44(10):2681–2687.
  • Wang L, Zhang Z, Wang Y, et al. Treatment of stroke with erythropoietin enhances neurogenesis and angiogenesis and improves neurological function in rats. Stroke. 2004;35(7):1732–1737.
  • Minnerup J, Heidrich J, Rogalewski A, et al. The efficacy of erythropoietin and its analogues in animal stroke models: a meta-analysis. Stroke. 2009;40(9):3113–3120.
  • Ehrenreich H, Weissenborn K, Prange H, et al. Recombinant human erythropoietin in the treatment of acute ischemic stroke. Stroke. 2009;40(12):e647–56.
  • Savitz SI. Cell therapies: careful translation from animals to patients. Stroke. 2013;44(6 Suppl 1):SS107–9.
  • Honmou O, Houkin K, Matsunaga T, et al. Intravenous administration of auto serum-expanded autologous mesenchymal stem cells in stroke. Brain. 2011;134(Pt 6):1790–1807.
  • Lee JS, Hong JM, Moon GJ, et al. A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke. Stem Cells. 2010;28(6):1099–1106.
  • Savitz SI, Misra V, Kasam M, et al. Intravenous autologous bone marrow mononuclear cells for ischemic stroke. Ann Neurol. 2011;70(1):59–69.
  • Schmidt A, Wellmann J, Schilling M, et al. Meta-analysis of the efficacy of different training strategies in animal models of ischemic stroke. Stroke. 2014;45(1):239–247.
  • Wolf SL, Winstein CJ, Miller JP, et al. Effect of constraint-induced movement therapy on upper extremity function 3 to 9 months after stroke: the EXCITE randomized clinical trial. JAMA. 2006;296(17):2095–2104.
  • Duncan P, Studenski S, Richards L, et al. Randomized clinical trial of therapeutic exercise in subacute stroke. Stroke. 2003;34(9):2173–2180.
  • Saunders DH, Sanderson M, Brazzelli M, et al. Physical fitness training for stroke patients. Cochrane Database Syst Rev. 2013;10:CD003316.
  • Mead GE, Hsieh C-F, Lee R, et al. Selective serotonin reuptake inhibitors for stroke recovery: a systematic review and meta-analysis. Stroke. 2013;44(3):844–850.
  • Barbas D, DesGroseillers L, Castellucci VF, et al. Multiple serotonergic mechanisms contributing to sensitization in aplysia: evidence of diverse serotonin receptor subtypes. Learn Mem. 2003;10(5):373–386.
  • Greene J, Banasr M, Lee B, et al. Vascular endothelial growth factor signaling is required for the behavioral actions of antidepressant treatment: pharmacological and cellular characterization. Neuropsychopharmacology. 2009;34(11):2459–2468.
  • Allaman I, Fiumelli H, Magistretti PJ, et al. Fluoxetine regulates the expression of neurotrophic/growth factors and glucose metabolism in astrocytes. Psychopharmacology (Berl). 2011;216(1):75–84.
  • Kennedy EP, Weiss SB. The function of cytidine coenzymes in the biosynthesis of phospholipides. J Biol Chem. 1956;222(1):193–214.
  • Yen CL, Mar MH, Zeisel SH. Choline deficiency-induced apoptosis in PC12 cells is associated with diminished membrane phosphatidylcholine and sphingomyelin, accumulation of ceramide and diacylglycerol, and activation of a caspase. Faseb J. 1999;13(1):135–142.
  • Adibhatla RM, Hatcher JF, Dempsey RJ. Effects of citicoline on phospholipid and glutathione levels in transient cerebral ischemia. Stroke. 2001;32(10):2376–2381.
  • Secades JJ. Citicoline: pharmacological and clinical review, 2010 update. Rev Neurol. 2011;52(Suppl 2):S1–S62.
  • Clark WM, Warach SJ, Pettigrew LC, et al. A randomized dose-response trial of citicoline in acute ischemic stroke patients. citicoline stroke study group. Neurology. 1997;49(3):671–678.
  • Clark WM, Williams BJ, Selzer KA, et al. A randomized efficacy trial of citicoline in patients with acute ischemic stroke. Stroke. 1999;30(12):2592–2597.
  • Clark WM, Wechsler LR, Sabounjian LA, et al. Citicoline stroke study group. A phase III randomized efficacy trial of 2000 mg citicoline in acute ischemic stroke patients. Neurology. 2001;57(9):1595–1602.
  • Dávalos A, Castillo J, Alvarez-Sabín J, et al. Oral citicoline in acute ischemic stroke: an individual patient data pooling analysis of clinical trials. Stroke. 2002;33(12):2850–2857.
  • Saver JL. Citicoline: update on a promising and widely available agent for neuroprotection and neurorepair. Rev Neurol Dis. 2008;5(4):167–177.
  • Zhang L, Zhang RL, Wang Y, et al. Functional recovery in aged and young rats after embolic stroke: treatment with a phosphodiesterase type 5 inhibitor. Stroke. 2005;36(4):847–852.
  • Wiessner C, Bareyre FM, Allegrini PR, et al. Anti-Nogo-A antibody infusion 24 hours after experimental stroke improved behavioral outcome and corticospinal plasticity in normotensive and spontaneously hypertensive rats. J Cereb Blood Flow Metab. 2003;23(2):154–165.
  • Papadopoulos CM, Tsai S-Y, Cheatwood JL, et al. Dendritic plasticity in the adult rat following middle cerebral artery occlusion and Nogo-a neutralization. Cereb Cortex. 2006;16(4):529–536.
  • Tsai S-Y, Papadopoulos CM, Schwab ME, et al. Delayed anti-nogo-a therapy improves function after chronic stroke in adult rats. Stroke. 2011;42(1):186–190.
  • Meininger V, Pradat P-F, Corse A, et al. Safety, pharmacokinetic, and functional effects of the nogo-a monoclonal antibody in amyotrophic lateral sclerosis: a randomized, first-in-human clinical trial. PLoS One. 2014;9(5):e97803.
  • Schmandke A, Schmandke A, Schwab ME. Nogo-A: Multiple Roles in CNS development, maintenance, and disease. Neuroscientist. 2014;20(4):372–386.
  • Schäbitz W-R, Kollmar R, Schwaninger M, et al. Neuroprotective effect of granulocyte colony-stimulating factor after focal cerebral ischemia. Stroke. 2003;34(3):745–751.
  • Schneider A, Krüger C, Steigleder T, et al. The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis. J Clin Invest. 2005;115(8):2083–2098.
  • Minnerup J, Heidrich J, Wellmann J, et al. Meta-analysis of the efficacy of granulocyte-colony stimulating factor in animal models of focal cerebral ischemia. Stroke. 2008;39(6):1855–1861.
  • 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.
  • Villa P, Bigini P, Mennini T, et al. Erythropoietin selectively attenuates cytokine production and inflammation in cerebral ischemia by targeting neuronal apoptosis. J Exp Med. 2003;198(6):971–975.
  • Li Y, Lu Z, Keogh CL, et al. Erythropoietin-induced neurovascular protection, angiogenesis, and cerebral blood flow restoration after focal ischemia in mice. J Cereb Blood Flow Metab. 2007;27(5):1043–1054.
  • Ehrenreich H, Hasselblatt M, Dembowski C, et al. Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med. 2002;8(8):495–505.
  • Savitz SI. Developing cellular therapies for stroke. Stroke. 2015;46(7):2026–2031.
  • Oki K, Tatarishvili J, Wood J, et al. Human-induced pluripotent stem cells form functional neurons and improve recovery after grafting in stroke-damaged brain. Stem Cells. 2012;30(6):1120–1133.
  • Tornero D, Wattananit S, Grønning Madsen M, et al. Human induced pluripotent stem cell-derived cortical neurons integrate in stroke-injured cortex and improve functional recovery. Brain. 2013;136(Pt 12):3561–3577.
  • Ohtaki H, Ylostalo JH, Foraker JE, et al. Stem/progenitor cells from bone marrow decrease neuronal death in global ischemia by modulation of inflammatory/immune responses. Proc Natl Acad Sci USA. 2008;105(38):14638–14643.
  • Sharma S, Yang B, Strong R, et al. Bone marrow mononuclear cells protect neurons and modulate microglia in cell culture models of ischemic stroke. J Neurosci Res. 2010;88(13):2869–2876.
  • Zhang P, Li J, Liu Y, et al. Human embryonic neural stem cell transplantation increases subventricular zone cell proliferation and promotes peri-infarct angiogenesis after focal cerebral ischemia. Neuropathology. 2011;31(4):384–391.
  • Tang Y, Wang J, Lin X, et al. Neural stem cell protects aged rat brain from ischemia-reperfusion injury through neurogenesis and angiogenesis. J Cereb Blood Flow Metab. 2014;34(7):1138–1147.
  • Kondziolka D, Wechsler L, Goldstein S, et al. Transplantation of cultured human neuronal cells for patients with stroke. Neurology. 2000;55(4):565–569.

••An important review on the pitfalls of cell-based therapies.

  • Boncoraglio GB, Bersano A, Candelise L, et al.. Stem cell transplantation for ischemic stroke. Cochrane Database Syst Rev. 2010 Sep 8;(9):CD007231.
  • Moniche F, Gonzalez A, Gonzalez-Marcos J-R, et al. Intra-arterial bone marrow mononuclear cells in ischemic stroke: a pilot clinical trial. Stroke. 2012;43(8):2242–2244.
  • Friedrich MAG, Martins MP, Araújo MD, et al. Intra-arterial infusion of autologous bone marrow mononuclear cells in patients with moderate to severe middle cerebral artery acute ischemic stroke. Cell Transplant. 2012;21(Suppl 1):S13–21.
  • Hess DC, Sila CA, Furlan AJ, et al. A double-blind placebo-controlled clinical evaluation of MultiStem for the treatment of ischemic stroke. Int J Stroke. 2014;9(3):381–386.
  • Ince LP. Behavioral psychology in rehabilitation medicine. Philadelphia: Williams & Wilkins; 1980.
  • Zhao C, Wang J, Zhao S, et al. Constraint-induced movement therapy enhanced neurogenesis and behavioral recovery after stroke in adult rats. Tohoku J Exp Med. 2009;218(4):301–308.
  • Müller HD, Hanumanthiah KM, Diederich K, et al. Brain-derived neurotrophic factor but not forced arm use improves long-term outcome after photothrombotic stroke and transiently upregulates binding densities of excitatory glutamate receptors in the rat brain. Stroke. 2008;39(3):1012–1021.
  • Diederich K, Quennet V, Bauer H, et al. Successful regeneration after experimental stroke by granulocyte-colony stimulating factor is not further enhanced by constraint-induced movement therapy either in concurrent or in sequential combination therapy. Stroke. 2012;43(1):185–192.
  • Janssen H, Speare S, Spratt NJ, et al. Exploring the efficacy of constraint in animal models of stroke: meta-analysis and systematic review of the current evidence. Neurorehabil Neural Repair. 2013;27(1):3–12.
  • Kwakkel G, Veerbeek JM, Van Wegen EEH, et al. Constraint-induced movement therapy after stroke. Lancet Neurol. 2015;14(2):224–234.

•A recent review on constraint-induced movement therapy after stroke.

  • Taub E, Crago JE, Burgio LD, et al. An operant approach to rehabilitation medicine: overcoming learned nonuse by shaping. J Exp Anal Behav. 1994;61(2):281–293.
  • Wolf SL, Winstein CJ, Miller JP, et al. Retention of upper limb function in stroke survivors who have received constraint-induced movement therapy: the EXCITE randomised trial. Lancet Neurol. 2008;7(1):33–40.
  • Langhorne P, Coupar F, Pollock A. Motor recovery after stroke: a systematic review. Lancet Neurol. 2009;8(8):741–754.

•A well-written review on physical treatments to enhance neural recovery.

  • Ploughman M, Attwood Z, White N, et al. Endurance exercise facilitates relearning of forelimb motor skill after focal ischemia. Eur J Neurosci. 2007;25(11):3453–3460.
  • Chang H-C, Yang Y-R, Wang S-GP, et al. Effects of treadmill training on motor performance and extracellular glutamate level in striatum in rats with or without transient middle cerebral artery occlusion. Behav Brain Res. 2009;205(2):450–455.
  • Lee S-U, Kim D-Y, Park S-H, et al. Mild to moderate early exercise promotes recovery from cerebral ischemia in rats. Can J Neurol Sci. 2009;36(4):443–449.
  • Luo C-X, Jiang J, Zhou Q-G, et al. Voluntary exercise-induced neurogenesis in the postischemic dentate gyrus is associated with spatial memory recovery from stroke. J Neurosci Res. 2007;85(8):1637–1646.
  • Duncan P, Richards L, Wallace D, et al. A randomized, controlled pilot study of a home-based exercise program for individuals with mild and moderate stroke. Stroke. 1998;29(10):2055–2060.
  • AVERT Trial Collaboration group. Efficacy and safety of very early mobilisation within 24 h of stroke onset (AVERT): a randomised controlled trial. Lancet. 2015 Jul 4;386(9988):46–55.
  • Walter J, Keiner S, Witte OW, et al. Age-related effects on hippocampal precursor cell subpopulations and neurogenesis. Neurobiol Aging. 2011;32(10):1906–1914.
  • Chen J, Ye X, Yan T, et al. Adverse effects of bone marrow stromal cell treatment of stroke in diabetic rats. Stroke. 2011;42(12):3551–3558.
  • ElAli A, Doeppner TR, Zechariah A, et al.Increased blood-brain barrier permeability and brain edema after focal cerebral ischemia induced by hyperlipidemia: role of lipid peroxidation and calpain-1/2, matrix metalloproteinase-2/9, and RhoA overactivation. Stroke. 2011;42(11):3238–3244.
  • Qu HL, Zhao M, Zhao SS, et al. Forced limb-use enhanced neurogenesis and behavioral recovery after stroke in the aged rats. Neuroscience. 2015;286:316–324.
  • Yan T, Chopp M, Ye X, et al. Niaspan increases axonal remodeling after stroke in type 1 diabetes rats. Neurobiol Dis. 2012;46(1):157–164.
  • Schmidt A, Minnerup J, Kleinschnitz C. Emerging neuro- protective drugs for the treatment of acute ischemic stroke. Expert Opin Emerg Drugs. 2013 Jun;18(2):109–120.
  • O’Collins VE, Macleod MR, Donnan GA, et al. 1,026 experimental treatments in acute stroke. Ann Neurol. 2006;59(3):467–477.

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