Modulation of Neural Plasticity as a Basis for Stroke Rehabilitation

Current understanding of the mechanisms underlying neural plasticity changes after stroke stems from experimental models as well as clinical studies and provides the foundation for evidence-based neurorehabilitation. In this review, we first describe the main structural and functional constituents of neural plasticity that are believed to contribute to recovery of function after stroke. Next, we discuss selected behavioral manipulations and adjuvant therapies that can stimulate neural plasticity and improve recovery of function, particularly when applied in combination with task-specific physiotherapy and in a stimulating environment. ### Experience-Dependent Plasticity of the Cerebral Cortex Cerebral cortex is an assembly of neuronal cells that are highly interconnected. The morphology as well as function of these complex and spatially distributed networks are modulated or even controlled by the glial component of the central nervous system (CNS). The ability to adapt in response to the changing environment is the most fundamental property of the nervous tissue and constitutes the basis for learning. Neural plasticity is the neurobiological basis for the ability to adapt and learn in an experience-dependent manner.1 At the structural level, neural plasticity could be defined in terms of dendritic and axonal arborization, spine density, synapse number and size, receptor density, and in some brain regions also the number of neurons. These structural constituents of neural plasticity jointly determine the complexity of neuronal networks and their activity and contribute to recovery of function after stroke and other CNS injury. ### Spontaneous Recovery of Function After Stroke Loss of function attributable to stroke is caused by cell death in the infarcted region as well as cell dysfunction in the areas surrounding the infarct. In addition, the function of remote brain regions, including the contralateral areas that are connected to the area of tissue damage, is compromised because of hypometabolism, neurovascular uncoupling, and aberrant neurotransmission, jointly called diaschisis.1 Some recovery of function occurs spontaneously after stroke in …

[1]  M. Schwab,et al.  Delayed Anti-Nogo-A Therapy Improves Function After Chronic Stroke in Adult Rats , 2011, Stroke.

[2]  I. Módy,et al.  Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke. , 2010, Nature.

[3]  Luke A. Henderson,et al.  Functional Reorganization of the Brain in Humans Following Spinal Cord Injury: Evidence for Underlying Changes in Cortical Anatomy , 2011, The Journal of Neuroscience.

[4]  S. Small,et al.  Action observation has a positive impact on rehabilitation of motor deficits after stroke , 2007, NeuroImage.

[5]  H. Toresson,et al.  The sigma-1 receptor enhances brain plasticity and functional recovery after experimental stroke. , 2011, Brain : a journal of neurology.

[6]  L. Xiong,et al.  TAT-NEP1-40 as a novel therapeutic candidate for axonal regeneration and functional recovery after stroke , 2011, Journal of drug targeting.

[7]  M. Gassmann,et al.  Post-acute delivery of erythropoietin induces stroke recovery by promoting perilesional tissue remodelling and contralesional pyramidal tract plasticity. , 2011, Brain : a journal of neurology.

[8]  S. C. Gandevia,et al.  Neuropathic pain and primary somatosensory cortex reorganization following spinal cord injury , 2009, PAIN®.

[9]  H. Seers,et al.  OUTCOME , 1977, How to Win Your Case.

[10]  M. Hallett,et al.  Multimodal imaging of brain reorganization in motor areas of the contralesional hemisphere of well recovered patients after capsular stroke. , 2006, Brain : a journal of neurology.

[11]  Randy F. Stout,et al.  Glial cells in (patho)physiology , 2012, Journal of neurochemistry.

[12]  Michel Modo,et al.  Implantation Site and Lesion Topology Determine Efficacy of a Human Neural Stem Cell Line in a Rat Model of Chronic Stroke , 2012, Stem cells.

[13]  Richard S. J. Frackowiak,et al.  The functional anatomy of motor recovery after stroke in humans: A study with positron emission tomography , 1991, Annals of neurology.

[14]  H. Karbe,et al.  Mirror Therapy Promotes Recovery From Severe Hemiparesis: A Randomized Controlled Trial , 2009, Neurorehabilitation and neural repair.

[15]  J. Bogousslavsky,et al.  Trafermin for stroke recovery: is it time for another randomized clinical trial? , 2011, Expert opinion on biological therapy.

[16]  M. Sofroniew,et al.  Astrocytes: biology and pathology , 2009, Acta Neuropathologica.

[17]  T. Wieloch,et al.  Mechanisms of neural plasticity following brain injury , 2006, Current Opinion in Neurobiology.

[18]  Jinah Kim,et al.  The Effects of Improvisational Music Therapy on Joint Attention Behaviors in Autistic Children: A Randomized Controlled Study , 2008, Journal of autism and developmental disorders.

[19]  B. Barres,et al.  Control of synapse number by glia. , 2001, Science.

[20]  M. Nilsson,et al.  Astrocyte activation and reactive gliosis , 2005, Glia.

[21]  B. Barres,et al.  Thrombospondins 1 and 2 are Necessary for Synaptic Plasticity and Functional Recovery after Stroke , 2008, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[22]  B. MacVicar,et al.  Calcium transients in astrocyte endfeet cause cerebrovascular constrictions , 2004, Nature.

[23]  K. Jin,et al.  VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. , 2003, The Journal of clinical investigation.

[24]  M. Sofroniew.  Molecular dissection of reactive astrogliosis and glial scar formation , 2009, Trends in Neurosciences.

[25]  Michael Nilsson,et al.  Serum IGF-I levels correlate to improvement of functional outcome after ischemic stroke. , 2011, The Journal of clinical endocrinology and metabolism.

[26]  William H. Frey,et al.  Non-invasive intranasal insulin-like growth factor-I reduces infarct volume and improves neurologic function in rats following middle cerebral artery occlusion , 2001, Neuroscience Letters.

[27]  J. Kleim,et al.  Neural Plasticity: The Biological Substrate For Neurorehabilitation , 2010, PM & R : the journal of injury, function, and rehabilitation.

[28]  M. Pekny,et al.  The role of astrocytes and complement system in neural plasticity. , 2007, International review of neurobiology.

[29]  L. Goldstein.  Amphetamine Trials and Tribulations , 2009, Stroke.

[30]  E. M. Rouiller,et al.  Mechanisms of recovery of dexterity following unilateral lesion of the sensorimotor cortex in adult monkeys , 1999, Experimental Brain Research.

[31]  G. Kartje,et al.  Neuronal Plasticity and Functional Recovery After Ischemic Stroke , 2008, Topics in stroke rehabilitation.

[32]  P. Eriksson,et al.  Increased Neurogenesis and Astrogenesis from Neural Progenitor Cells Grafted in the Hippocampus of GFAP−/−Vim−/− Mice , 2007, Stem cells.

[33]  John W Krakauer,et al.  Early imaging correlates of subsequent motor recovery after stroke , 2009, Annals of neurology.

[34]  Steven C. Cramer.  Repairing the human brain after stroke: I. Mechanisms of spontaneous recovery , 2008, Annals of neurology.

[35]  J. Hell,et al.  Thrombospondins Are Astrocyte-Secreted Proteins that Promote CNS Synaptogenesis , 2005, Cell.

[36]  A. Hannan,et al.  Enriched environments, experience-dependent plasticity and disorders of the nervous system , 2006, Nature Reviews Neuroscience.

[37]  F. Müller,et al.  Effect of levodopa in combination with physiotherapy on functional motor recovery after stroke: a prospective, randomised, double-blind study , 2001, The Lancet.

[38]  S. Knecht,et al.  Granulocyte-Colony Stimulating Factor (G-CSF) in Stroke Patients with Concomitant Vascular Disease—A Randomized Controlled Trial , 2011, PloS one.

[39]  Heidi Johansen-Berg,et al.  Functional MRI Correlates of Lower Limb Function in Stroke Victims With Gait Impairment , 2008, Stroke.

[40]  Yu-Ching Lin,et al.  Human Umbilical Mesenchymal Stem Cells Promote Recovery After Ischemic Stroke , 2011, Stroke.

[41]  M. Farooq,et al.  Role of Sildenafil in Neurological Disorders , 2008, Clinical neuropharmacology.

[42]  A. Álvarez-Buylla,et al.  For the Long Run Maintaining Germinal Niches in the Adult Brain , 2004, Neuron.

[43]  A. Zechariah,et al.  Combination of Tissue-Plasminogen Activator With Erythropoietin Induces Blood–Brain Barrier Permeability, Extracellular Matrix Disaggregation, and DNA Fragmentation After Focal Cerebral Ischemia in Mice , 2010, Stroke.

[44]  Pia Rotshtein,et al.  Pleasant music overcomes the loss of awareness in patients with visual neglect , 2009, Proceedings of the National Academy of Sciences.

[45]  S. Strittmatter,et al.  Nogo Receptor Antagonism Promotes Stroke Recovery by Enhancing Axonal Plasticity , 2004, The Journal of Neuroscience.

[46]  I. Peretz,et al.  Music listening enhances cognitive recovery and mood after middle cerebral artery stroke. , 2008, Brain : a journal of neurology.

[47]  N. Sims,et al.  Mitochondrial Glutathione: A Modulator of Brain Cell Death , 2004, Journal of bioenergetics and biomembranes.

[48]  M. Chopp,et al.  Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation , 2012, The Lancet Neurology.

[49]  M. Chopp,et al.  Niaspan increases angiogenesis and improves functional recovery after stroke , 2007, Annals of neurology.

[50]  W. McIlroy,et al.  Effectiveness of Virtual Reality Using Wii Gaming Technology in Stroke Rehabilitation: A Pilot Randomized Clinical Trial and Proof of Principle , 2010, Stroke.

[51]  P. Carmeliet,et al.  Protective Role of Reactive Astrocytes in Brain Ischemia , 2008, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[52]  P. Eriksson,et al.  Response to Comment on "Human Neuroblasts Migrate to the Olfactory Bulb via a Lateral Ventricular Extension" , 2007, Science.

[53]  Leif Hertz,et al.  Bioenergetics of cerebral ischemia: A cellular perspective , 2008, Neuropharmacology.

[54]  R. Zatorre,et al.  Music, the food of neuroscience? , 2005, Nature.

[55]  S. Page,et al.  Mental Practice in Chronic Stroke: Results of a Randomized, Placebo-Controlled Trial , 2007, Stroke.

[56]  D. J. Felleman,et al.  Topographic reorganization of somatosensory cortical areas 3b and 1 in adult monkeys following restricted deafferentation , 1983, Neuroscience.

[57]  O. Lindvall,et al.  Cross-talk between neural stem cells and immune cells: the key to better brain repair? , 2012, Nature Neuroscience.

[58]  M. Hallett,et al.  Contribution of the ipsilateral motor cortex to recovery after chronic stroke , 2003, Annals of neurology.

[59]  D. Geschwind,et al.  Inosine Augments the Effects of a Nogo Receptor Blocker and of Environmental Enrichment to Restore Skilled Forelimb Use after Stroke , 2011, The Journal of Neuroscience.

[60]  Davis M. Glasser,et al.  Effects of Action Observation on Physical Training After Stroke , 2008, Stroke.

[61]  N. Wilczak,et al.  Insulin-Like Growth Factor I Serum Levels Influence Ischemic Stroke Outcome , 2011, Stroke.

[62]  B. Kolb,et al.  Cerebral Cortex doi:10.1093/cercor/bhi132 Dendritic Plasticity in the Adult Rat Following Middle Cerebral Artery , 2005 .

[63]  W. Young,et al.  Insulin Growth Factor-1 Gene Transfer Enhances Neurovascular Remodeling and Improves Long-Term Stroke Outcome in Mice , 2008, Stroke.

[64]  P. Verschure,et al.  Virtual reality based rehabilitation speeds up functional recovery of the upper extremities after stroke: a randomized controlled pilot study in the acute phase of stroke using the rehabilitation gaming system. , 2011, Restorative neurology and neuroscience.

[65]  W. Schäbitz,et al.  Granulocyte-colony stimulating factor for stroke treatment: mechanisms of action and efficacy in preclinical studies , 2009, Experimental & Translational Stroke Medicine.

[66]  T. Schormann,et al.  Mobilisation of Hematopoietic CD34+ Precursor Cells in Patients with Acute Stroke Is Safe - Results of an Open-Labeled Non Randomized Phase I/II Trial , 2011, PloS one.

[67]  R. Zorec,et al.  Astrocytes Negatively Regulate Neurogenesis Through the Jagged1‐Mediated Notch Pathway , 2012, Stem cells.

[68]  M. Chopp,et al.  One-Year Follow-Up After Bone Marrow Stromal Cell Treatment in Middle-Aged Female Rats With Stroke , 2007, Stroke.

[69]  B. Zörner,et al.  Anti‐Nogo on the go: from animal models to a clinical trial , 2010, Annals of the New York Academy of Sciences.

[70]  D. Chen,et al.  Robust neural integration from retinal transplants in mice deficient in GFAP and vimentin , 2003, Nature Neuroscience.

[71]  L. Cohen,et al.  Neuroplasticity in the context of motor rehabilitation after stroke , 2011, Nature Reviews Neurology.

[72]  M. Chopp,et al.  Recovery in a Patient with Locked-In Syndrome , 2006, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[73]  O. Lindvall,et al.  Neuronal replacement from endogenous precursors in the adult brain after stroke , 2002, Nature Medicine.

[74]  Michael Nilsson,et al.  A Systematic Review and Meta-Analysis of Erythropoietin in Experimental Stroke , 2010, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[75]  M. Chopp,et al.  Erythropoietin in Combination of Tissue Plasminogen Activator Exacerbates Brain Hemorrhage When Treatment Is Initiated 6 Hours After Stroke , 2010, Stroke.

[76]  Karl H. Plate,et al.  Angiogenesis after cerebral ischemia , 2009, Acta Neuropathologica.

[77]  M. Chopp,et al.  Functional Recovery in Aged and Young Rats After Embolic Stroke: Treatment With a Phosphodiesterase Type 5 Inhibitor , 2005, Stroke.

[78]  M. Chopp,et al.  Bone Marrow Stromal Cells Promote Skilled Motor Recovery and Enhance Contralesional Axonal Connections After Ischemic Stroke in Adult Mice , 2011, Stroke.

[79]  T. Murphy,et al.  Plasticity during stroke recovery: from synapse to behaviour , 2009, Nature Reviews Neuroscience.

[80]  M. Chopp,et al.  Delayed Administration of Human Umbilical Tissue-Derived Cells Improved Neurological Functional Recovery in a Rodent Model of Focal Ischemia , 2011, Stroke.

[81]  M. Chopp,et al.  Adverse Effects of Bone Marrow Stromal Cell Treatment of Stroke in Diabetic Rats , 2011, Stroke.

[82]  B. Johansson,et al.  Current trends in stroke rehabilitation. A review with focus on brain plasticity , 2011, Acta neurologica Scandinavica.

[83]  Derick T Wade,et al.  The clinical aspects of mirror therapy in rehabilitation: a systematic review of the literature , 2011, International journal of rehabilitation research. Internationale Zeitschrift fur Rehabilitationsforschung. Revue internationale de recherches de readaptation.

[84]  M. Schwab,et al.  Functional recovery and neuroanatomical plasticity following middle cerebral artery occlusion and IN‐1 antibody treatment in the adult rat , 2002, Annals of neurology.

[85]  Isabelle Peretz,et al.  Music and Speech Listening Enhance the Recovery of Early Sensory Processing after Stroke , 2010, Journal of Cognitive Neuroscience.

[86]  Nadia Bolognini,et al.  Using non-invasive brain stimulation to augment motor training-induced plasticity , 2009, Journal of NeuroEngineering and Rehabilitation.

[87]  D. Geschwind,et al.  Inosine Alters Gene Expression and Axonal Projections in Neurons Contralateral to a Cortical Infarct and Improves Skilled Use of the Impaired Limb , 2009, The Journal of Neuroscience.

[88]  Patrick McElduff,et al.  An Enriched Environment Improves Sensorimotor Function Post-Ischemic Stroke , 2010, Neurorehabilitation and neural repair.

[89]  C. Sommer,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 , 2008, Stroke.

[90]  Milos Pekny,et al.  Re-establishing the regenerative potential of central nervous system axons in postnatal mice , 2005, Journal of Cell Science.

[91]  C. Schuster,et al.  Dexamphetamine Improves Upper Extremity Outcome During Rehabilitation After Stroke , 2011, Neurorehabilitation and neural repair.

[92]  Aaron R. Seitz,et al.  Benefits of multisensory learning , 2008, Trends in Cognitive Sciences.

[93]  G. Schlaug,et al.  Bihemispheric brain stimulation facilitates motor recovery in chronic stroke patients , 2010, Neurology.

[94]  M. Lotze,et al.  Motor imagery , 2006, Journal of Physiology-Paris.

[95]  M. Chopp,et al.  Contralesional Axonal Remodeling of the Corticospinal System in Adult Rats After Stroke and Bone Marrow Stromal Cell Treatment , 2008, Stroke.

[96]  J. Sinden,et al.  The Neural Stem Cell Line CTX0E03 Promotes Behavioral Recovery and Endogenous Neurogenesis After Experimental Stroke in a Dose-Dependent Fashion , 2009, Neurorehabilitation and neural repair.

[97]  Brian Silver,et al.  Sildenafil treatment of subacute ischemic stroke: a safety study at 25-mg daily for 2 weeks. , 2009, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[98]  M. Chopp,et al.  Tadalafil, a long-acting type 5 phosphodiesterase isoenzyme inhibitor, improves neurological functional recovery in a rat model of embolic stroke , 2006, Brain Research.

[99]  Takuya Matsunaga,et al.  Intravenous administration of auto serum-expanded autologous mesenchymal stem cells in stroke. , 2011, Brain : a journal of neurology.

[100]  P. Fisher,et al.  β-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression , 2005, Nature.

[101]  R. P. Stroemer,et al.  Enhanced neocortical neural sprouting, synaptogenesis, and behavioral recovery with D-amphetamine therapy after neocortical infarction in rats. , 1998, Stroke.

[102]  A. Michotte,et al.  Boosting endogenous neuroprotection in multiple sclerosis: the ASsociation of Inosine and Interferon β in relapsing- remitting Multiple Sclerosis (ASIIMS) trial , 2010, Multiple sclerosis.

[103]  S. Cramer,et al.  Motor Cortex Organization After Stroke Is Related to Side of Stroke and Level of Recovery , 2003, Stroke.

[104]  Mark Ellisman,et al.  Absence of Glial Fibrillary Acidic Protein and Vimentin Prevents Hypertrophy of Astrocytic Processes and Improves Post-Traumatic Regeneration , 2004, The Journal of Neuroscience.

[105]  A. Ghazanfar,et al.  Is neocortex essentially multisensory? , 2006, Trends in Cognitive Sciences.

[106]  T. Wieloch,et al.  Levodopa Treatment Improves Functional Recovery After Experimental Stroke , 2012, Stroke.

[107]  M. Chopp,et al.  Sildenafil (Viagra) Induces Neurogenesis and Promotes Functional Recovery After Stroke in Rats , 2002, Stroke.

[108]  John D. Lambris,et al.  The Classical Complement Cascade Mediates CNS Synapse Elimination , 2007, Cell.

[109]  T. Murphy,et al.  In Vivo Voltage-Sensitive Dye Imaging in Adult Mice Reveals That Somatosensory Maps Lost to Stroke Are Replaced over Weeks by New Structural and Functional Circuits with Prolonged Modes of Activation within Both the Peri-Infarct Zone and Distant Sites , 2009, The Journal of Neuroscience.

[110]  M. Schwab,et al.  Intrathecal treatment with anti-Nogo-A antibody improves functional recovery in adult rats after stroke , 2007, Experimental Brain Research.

[111]  M. Chopp,et al.  Niacin Treatment of Stroke Increases Synaptic Plasticity and Axon Growth in Rats , 2010, Stroke.

[112]  R. Sidman,et al.  Communication via gap junctions underlies early functional and beneficial interactions between grafted neural stem cells and the host , 2010, Proceedings of the National Academy of Sciences.

[113]  M. Schwab,et al.  Anti—Nogo-A Antibody Infusion 24 Hours after Experimental Stroke Improved Behavioral Outcome and Corticospinal Plasticity in Normotensive and Spontaneously Hypertensive Rats , 2003, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[114]  M. Walker,et al.  Granulocyte-Colony Stimulating Factor for Mobilizing Bone Marrow Stem Cells in Subacute Stroke: The Stem Cell Trial of Recovery Enhancement After Stroke 2 Randomized Controlled Trial , 2012, Stroke.

[115]  H. Vosper.  Niacin: a re‐emerging pharmaceutical for the treatment of dyslipidaemia , 2009, British journal of pharmacology.

[116]  H. Reichmann,et al.  Recombinant Human Erythropoietin in the Treatment of Acute Ischemic Stroke , 2009, Stroke.

[117]  F. Chollet,et al.  Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial , 2011, The Lancet Neurology.

[118]  L. Cohen,et al.  Reorganization of the human ipsilesional premotor cortex after stroke. , 2004, Brain : a journal of neurology.

[119]  H. Stam,et al.  Mirror therapy improves hand function in subacute stroke: a randomized controlled trial. , 2008, Archives of physical medicine and rehabilitation.

[120]  C. Sommer,et al.  Intravenous Brain-Derived Neurotrophic Factor Enhances Poststroke Sensorimotor Recovery and Stimulates Neurogenesis , 2007, Stroke.

[121]  M. Chopp,et al.  Niaspan Treatment Increases Tumor Necrosis Factor-α-Converting Enzyme and Promotes Arteriogenesis after Stroke , 2009, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[122]  G. Dawson,et al.  L-655,708 enhances cognition in rats but is not proconvulsant at a dose selective for α5-containing GABAA receptors , 2006, Neuropharmacology.

[123]  J. Homberg,et al.  Fluoxetine Exerts Age-Dependent Effects on Behavior and Amygdala Neuroplasticity in the Rat , 2011, PloS one.

[124]  R. Zatorre,et al.  Listening to musical rhythms recruits motor regions of the brain. , 2008, Cerebral cortex.

[125]  M. Pekny,et al.  Astrocyte intermediate filaments in CNS pathologies and regeneration , 2004, The Journal of pathology.

[126]  B. Bussel,et al.  Longitudinal Study of Motor Recovery After Stroke: Recruitment and Focusing of Brain Activation , 2002, Stroke.

[127]  E. Jankowska,et al.  How Can Corticospinal Tract Neurons Contribute to Ipsilateral Movements? A Question With Implications for Recovery of Motor Functions , 2006, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[128]  M. Chopp,et al.  Remodeling of the Corticospinal Innervation and Spontaneous Behavioral Recovery After Ischemic Stroke in Adult Mice , 2009, Stroke.

[129]  Rüdiger J. Seitz,et al.  Post-lesional cerebral reorganisation: Evidence from functional neuroimaging and transcranial magnetic stimulation , 2006, Journal of Physiology-Paris.

[130]  Nicola J. Platt,et al.  The Roles of BDNF, pCREB and Wnt3a in the Latent Period Preceding Activation of Progenitor Cell Mitosis in The Adult Dentate Gyrus by Fluoxetine , 2010, PloS one.

[131]  Alexander W Dromerick,et al.  Rehabilitation After Stroke: Current State of the Science , 2010, Current neurology and neuroscience reports.

[132]  B. Kolb,et al.  Inosine induces axonal rewiring and improves behavioral outcome after stroke , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[133]  A. Cocchiarella.  Partial motor restoration upon administration of sildenafil: a case study , 2012, Developmental neurorehabilitation.

[134]  M Chopp,et al.  VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain. , 2000, The Journal of clinical investigation.

[135]  S. Eksborg,et al.  Should Amphetamines Be Given to Improve Recovery After Stroke? , 2007 .