Stroke is the second to third most common cause of death in adults, and more than a third of people who survive a stroke will have severe disability. Therapeutic options currently centre on fibrinolytic treatment, but its limitations restrict use to a small proportion of patients. Although a wide range of neuroprotective substances has been effective in experimental models, they have repeatedly failed in clinical trials because of toxicity or loss of effectiveness. Recent strategies based on neuroplasticity and cellular therapy have shown significant efficacy in improving functional recovery in experimental models, although further study is still necessary to clarify how the brain responds to ischaemic damage and is able to reorganize itself in the long term. Although steps must still be taken to ensure the safety and feasibility of treatments based on neuroplasticity and cellular therapy, neurorepair strategies provide promising future therapeutic options for stroke.

1.
Tackling the global burden of stroke. Lancet Neurol 2005;4:689.
2.
Rossini PM, Calautti C, Pauri F, Baron JC: Post-stroke plastic reorganization in the adult brain. Lancet Neurol 2003;2:493–502.
3.
Ramón y Cajal S: Estructura de los centros nerviosos de las aves. Rev Trimest Histol Norm Pat 1888;1:1–10.
4.
Ramón y Cajal S: Sur la structure de l’écorce cérébrale de quelques mammifères. Cellule 1891;7:123–176.
5.
Berlucchi G: The origin of the term plasticity in the neurosciences: Ernesto Lugaro and chemical synaptic transmission. J Hist Neurosci 2002;11:305–309.
6.
Hebb DO: The effects of early experience on problem solving at maturity. Am Psychol 1947;2:737–745.
7.
Kwakkel G, Kollen B, Lindeman E: Understanding the pattern of functional recovery after stroke: facts and theories. Restor Neurol Neurosci 2004;22:281–299.
8.
Weber R, Ramos-Cabrer P, Hoehn M: Present status of magnetic resonance imaging and spectroscopy in animal stroke models. J Cereb Blood Flow Metab 2006;26:591–604.
9.
Boniface SJ: Plasticity after acute ischemic stroke studied by transcranial magnetic stimulation. J Neurol Neurosurg Psychiatry 2001;71:713–715.
10.
Dirnagl U, Iadecola C, Moskowitz MA: Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 1999;22:391–397.
11.
Hurtado O, Pradillo JM, Alonso-Escolano D, Lorenzo P, Sobrino T, Castillo J, Lizasoain I, Moro MA: Neurorepair versus neuroprotection in stroke. Cerebrovasc Dis 2006;21:54–63.
12.
Cramer SC, Chopp M: Recovery recapitulates ontogeny. Trends Neurosci 2000;23:265–271.
13.
Johansson B: Brain plasticity and stroke rehabilitation: the Willis lecture. Stroke 2000;31:223–230.
14.
Stork O, Welzl H: Memory formation and the regulation of gene expression. Cell Mol Life Sci 1999;55:575–592.
15.
Carmichael ST, Archibeque I, Luke L, Nolan T, Momiy J, Li S: Growth-associated gene expression after stroke: evidence for a growth-promoting region in peri-infarct cortex. Exp Neurol 2005;193:291–311.
16.
Ward NS: Neural plasticity and recovery of function. Prog Brain Res 2005;150:527–535.
17.
Seil FJ: Recovery and repair issues after stroke from the scientific perspective. Curr Opin Neurol 1997;10:49–51.
18.
Martinez-Vila E, Irimia P: Challenges of neuroprotection and neurorestoration in ischemic stroke treatment. Cerebrovasc Dis 2005;20:148–158.
19.
Zemke AC, Heagerty PJ, Lee C, Cramer SC: Motor cortex reorganization after the stroke is related to side of stroke and level of recovery. Stroke 2003;34:e23-e28.
20.
Carmichael ST: Plasticity of cortical projections after stroke. Neuroscientist 2003;9:64–75.
21.
Boroojerdi B, Ziemann U, Chen R, Bütefisch CM, Cohen LG: Mechanisms underlying human motor system plasticity. Muscle Nerve 2001;24:602–613.
22.
Cooke SF, Bliss TVP: Plasticity in the human central nervous system. Brain 2006;129:1659–1673.
23.
Pfeiffer BE, Huber KM: Current advances in local protein synthesis and synaptic plasticity. J Neurosci 2006;26:7147–7150.
24.
Hammond C, Crepel V, Gozlan H, Ben-Ari Y: Anoxic LTP sheds light on the multiple facets of NMDA receptors. Trends Neurosci 1994;17:497–503.
25.
Yuste R, Bonhoeffer T: Morphological changes associated with long-term synaptic plasticity. Annu Rev Neurosci 2001;24:1071–1089.
26.
Calabresi P, Centonze D, Pisani A, Cupini LM, Bernardi G: Synaptic plasticity in the ischemic brain. Lancet Neurol 2003;2:622–629.
27.
Hsu KS, Huang CC: Characterization of the anoxia-induced long-term synaptic potentiation in area CA1 of the rat hippocampus. Br J Pharmacol 1997;122:671–681.
28.
Picconi B, Tortiglione A, Barone I, Centonze D, Gardoni F, Gubellini P, Bonsi P, Pisani A, Bernardi G, Di Luca M, Calabresi P: NR2B subunit exerts a critical role in postischemic synaptic plasticity. Stroke 2006;37:1895–1901.
29.
Buonomano DV, Merzenich MM: Net interaction between different forms of short-term synaptic plasticity and slow-IPSPs in the hippocampus and auditory cortex. J Neurophysiol 1998;88:1765–1774.
30.
Toni N, Buchs PA, Nikonenko I, Bron CR, Muller D: LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite. Nature 1999;402:421–425.
31.
Javaherian A, Cline HT: Coordinated motor neuron axon growth and neuromuscular synaptogenesis are promoted by CPG15 in vivo. Neuron 2005;45:505–521.
32.
Carmichael ST: Cellular and molecular mechanisms of neural repair alter stroke: making waves. Ann Neurol 2006;59:735–742.
33.
Carmichael ST: Gene expression changes after stroke and traumatical brain injuries. Curr Opin Neurol 2003;26:699–704.
34.
Carulli D, Buffo A, Strata P: Reparative mechanisms in the cerebellar cortex. Prog Neurobiol 2004;72:373–398.
35.
Benowitz LI, Routtenberg A: GAP-43: an intrinsic determinant of neuronal development and plasticity. Trends Neurosci 1997;20:84–91.
36.
Caroni P: New EMBO members’ review: actin cytoskeleton regulation through modulation of PI(4,5)P(2) rafts. EMBO J 2001;20:4332–4336.
37.
Frey D, Laux T, Xu L, Schneider C, Caroni P: Shared and unique roles of CAP23 and GAP43 in actin regulation, neurite outgrowth and anatomical plasticity. J Cell Biol 2000;149:1443–1454.
38.
Hayashi T, Nochita N, Sugawara T, Chan PK: Temporal profile of angiogenesis and expression of related genes in the brain after ischemia. J Cereb Blood Flow Metab 2003;23:166–180.
39.
Harris KM: Structure, development and plasticity of dendritic spines. Curr Opin Neurobiol 1999;9:343–348.
40.
Nimchinsky EA, Sabatini BL, Svoboda K: Structure and function of dendritic spines. Annu Rev Physiol 2002;64:313–353.
41.
Peters A, Kaiserman-Abramhof IR: The small pyramidal neuron of the rat cerebral cortex. The perikaryon, dendrites and spines. Am J Anat 1970;127:321–355.
42.
Fischer M, Kaech S, Knutti D, Matus A: Rapid actin-based plasticity in dendritic spines. Neuron 1998;20:847–854.
43.
Dunaevsky A, Tashiro A, Majewska A, Mason C, Yuste R: Developmental regulation of spine motility in the mammalian central nervous system. Proc Natl Acad Sci USA 1999;96:13438–13443.
44.
Matus A: Postsynaptic actin and neuronal plasticity. Curr Opin Neurobiol 1999;5:561–565.
45.
Parnass Z, Tashiro A, Yuste R: Analysis of spine morphological plasticity in developing hippocampal pyramidal neurons. Hippocampus 2000;10:561–568.
46.
Majewska A, Tashiro A, Yuste R: Regulation of spine calcium dynamics by rapid spine motility. J Neurosci 2000;20:8262–8268.
47.
Yuste R, Majewska A, Holthoff K: From form to function: calcium compartmentalization in dendritic spines. Nat Neurosci 2000;3:653–659.
48.
Walikonis RS, Jensen ON, Mann M, Provance DW Jr, Mercer JA, Kennedy MB: Identification of proteins in the postsynaptic density fraction by mass spectrometry. J Neurosci 2000;20:4069–4080.
49.
Lippman J, Dunaevsky A: Dendritic spine morphogenesis and plasticity. J Neurobiol 2005;64:47–57.
50.
Christopherson KS, Ullian EM, Stokes CCA, Mullowney CE, Hell JW, Agah A, Lawier J, Mosher DF, Bornstein P, Barres BA: Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis. Cell 2005;120:421–433.
51.
Johansson BB, Belichenko PV: Neuronal plasticity and dendritic spines: effect on environmental enrichment on intact and postischemic rat brain. J Cereb Blood Flow Metab 2002;22:89–96.
52.
Zhang S, Boyd J, Delaney K, Murphy TH: Rapid reversible changes in dendritic spine structure in vivo gated by the degree of ischemia. J Neurosci 2005;25:5333–5338.
53.
Ito U, Kuroiwa T, Nagasao J, Kawakami E, Oyanagi K: Temporal profiles of axon terminals, synapses and spines in the ischemic penumbra of the cerebral cortex: ultrastructure of neuronal remodeling. Stroke 2006;37:2134–2139.
54.
Corbett D, Giles T, Evans S, McLean J, Biernaskie J: Dynamic changes in CA1 dendritic spines associated with ischemic tolerance. Exp Neurol 2006;202:133–138.
55.
Galliciotti G, Sonderegger P: Neuroserpin. Front Biosci 2006;11:33–45.
56.
Miranda E, Lomas DA: Neuroserpin, a serpin to think about. Cell Mol Life Sci 2006;63:709–722.
57.
Samson AL, Medcalf RL: Tissue-type plasminogen activator: a multifaceted modulator of neurotransmission and synaptic plasticity. Neuron 2006;50:673–678.
58.
Carmeliet P: Mechanisms of angiogenesis and arteriogenesis. Nat Med 2000;6:389–395.
59.
Felmeden DC, Blann AD, Lip GYH: Angiogenesis: basic pathophysiology and implications for disease. Eur Heart J 2003;24:586–603.
60.
Conway EM, Collen D, Carmeliet P: Molecular mechanisms of blood vessel growth. Cardiovasc Res 2001;49:507–521.
61.
Wei L, Erinjeri JP, Rovanein CM, Woolsey TA: Collateral growth and angiogenesis around cortical stroke. Stroke 2001;32:2179–2184.
62.
Zhang ZG, Zhang L, Tsang W, Soltanian-Zadeh H, Morris D, Zhang R, Goussev A, Powers C, Yeich T, Chopp M: Correlation of VEGF and angiopoietin expression with disruption of blood-brain barrier and angiogenesis after focal cerebral ischemia. J Cereb Blood Flow Metab 2002;22:379–392.
63.
Wang L, Zhang Z, Wang Y, Zhang R, Chopp M: Treatment of stroke with erythropoietin enhances neurogenesis and angiogenesis and improves neurological function in rats. Stroke 2004;35:1732–1737.
64.
Lawler J: Thrombospondin-1 as an endogenous inhibitor of angiogenesis and tumor growth. J Cell Mol Med 2002;6:1–12.
65.
Sun Y, Jin K, Xie L, Childs J, Mao XO, Logvinova A, Greenberg DA: VEGF-induced neuroprotection, neurogenesis and angiogenesis after focal cerebral ischemia. J Clin Invest 2003;111:1843–1851.
66.
Chen J, Zhang ZG, Li Y, Wang Y, Wang L, Jiang H, Zhang C, Lu M, Katakowski M, Feldkamp CS, Chopp M: Statins induce angiogenesis, neurogenesis and synaptogenesis after stroke. Ann Neurol 2003;53:743–751.
67.
Chen J, Chunling Z, Jiang H, Li Y, Zhang L, Robin A, Katakowski M, Lu M, Chopp M: Atorvastatin induction of VEGF and BDNF promotes brain plasticity after stroke in mice. J Cereb Blood Flow Metab 2005;25:281–290.
68.
Zhang L, Zhang RL, Wang Y, Zhang C, Zhang ZG, Meng H, Chopp M: Functional recovery in aged and young rats after embolic stroke: treatment with a phosphodiesterase type 5 inhibitor. Stroke 2005;36:847–852.
69.
Zhang R, Wang L, Zhang L, Chen J, Zhu Z, Zhang Z, Chopp M: Nitric oxide enhances angiogenesis via the synthesis of vascular endothelial growth factor and cGMP after stroke in the rat. Circ Res 2003;92:308–313.
70.
Losordo DW, Dimmeler S: Therapeutic angiogenesis and vasculogenesis for ischemic disease. I. Angiogenic cytokines. Circulation 2004;109:2487–2491.
71.
Wei L, Keogh CL, Whitaker VR, Theus MH, Yu SP: Angiogenesis and stem cell transplantation as potential treatments of cerebral ischemic stroke. Pathophysiology 2005;12:47–63.
72.
Meairs S, Wahlgren N, Dirnagl U, Lindvall O, Rothwell P, Baron JC, Hossmann K, Engelhardt B, Ferro J, McCulloch J, Kaste M, Endres M, Koistinaho J, Planas A, Vivien D, Dijkhuizen R, Czlonkowska A, Hagen A, Evans A, De Libero G, Nagy Z, Rastenyte D, Reess J, Davalos A, Lenzi GL, Amarenco P, Hennerici M: Stroke research priorities for the next decade – a representative view of the European scientific community. Cerebrovasc Dis 2006;22:75–82.
73.
Körbling M, Estrov Z: Adult stem cells for tissue repair – a new therapeutic concept? N Engl J Med 2003;349:570–582.
74.
Szentirmai O, Carter BS: Genetic and cellular therapies for cerebral infarction. Neurosurgery 2004;55:283–297.
75.
Savitz SI, Dinsmore JH, Wechsler LR, Rosenbaum DM, Caplan LR: Cell therapy for stroke. NeuroRx 2004;1:406–414.
76.
Haas S, Weidner N, Winkler J: Adult stem cell therapy in stroke. Curr Opin Neurol 2005;18:59–64.
77.
Shyu WC, Lee YJ, Liu DD, Lin SZ, Li H: Homing cells, cell therapy and stroke. Front Biosci 2006;11:899–907.
78.
Chopp M, Li Y: Treatment of neural injury with marrow stromal cells. Lancet Neurol 2002;1:92–100.
79.
Johannson BB: Functional and cellular effects of environmental enrichment after experimental brain infarcts. Restor Neurol Neurosci 2004;22:163–174.
80.
Chen CP, Lee YJ, Chiu ST, Shyu WC, Lee MY, Huang SP, Li H: The application of stem cells in the treatment of ischemic diseases. Histol Histopathol 2006;21:1209–1216.
81.
Li Y, Chen J, Chopp M: Adult bone marrow transplantation after stroke in adult rats. Cell Transplant 2001;10:31–40.
82.
Chen J, Li Y, Chopp M: Intracerebral transplantation of bone marrow with BDNF after MCAo in rat. Neuropharmacology 2000;39:711–716.
83.
Li Y, Chen J, Chen XG, Wang L, Gautam SC, Xu YX, Katakowksi M, Zhang LJ, Lu M, Janakiraman N, Chopp M: Human marrow stromal cell therapy for stroke in rat: neurotrophins and functional recovery. Neurology 2002;59:514–523.
84.
Li Y, Chen J, Wang L, Lu M, Chopp M: Treatment of stroke in rat with intracarotid administration of marrow stromal cells. Neurology 2001;56:1666–1672.
85.
Shen LH, Li Y, Chen J, Zhang J, Vanguri P, Borneman J, Chopp M: Intracarotid transplantation of bone marrow stromal cells increases axon-myelin remodeling after stroke. Neuroscience 2006;137:393–399.
86.
Chen J, Li Y, Wang L, Zhang Z, Lu D, Lu M, Chopp M: Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 2001;32:1005–1011.
87.
Chen J, Zhang ZG, Li Y, Wang L, Xu YX, Gautam SC, Lu M, Zhu Z, Chopp M: Intravenous administration of human bone marrow stromal cells induces angiogenesis in the ischemic boundary zone after stroke in rats. Circ Res 2003;92:692–699.
88.
Chen J, Li Y, Katakowski M, Chen X, Wang L, Lu D, Lu M, Gautam SC, Chopp M: Intravenous bone marrow stromal cell therapy reduces apoptosis and promotes endogenous cell proliferation after stroke in female rat. J Neurosci Res 2003;73:778–786.
89.
Li Y, Chopp M, Chen J, Wang L, Gautam SC, Xu X, Zhang Z: Intrastriatal transplantation of bone marrow nonhematopoietic cells improves functional recovery after stroke in adult mice. J Cereb Blood Flow Metab 2000;20:1311–1319.
90.
Yoshimura S, Takagi Y, Harada J, Teramoto T, Thomas SS, Waeber C, Bakowska JC, Breakefield XO, Moskowitz MA: FGF-2 regulation of neurogenesis in adult hippocampus after brain injury. Proc Natl Acad Sci USA 2001;98:5874–5879.
91.
Zhang C, Li Y, Chen J, Gao Q, Zacharek A, Kapke A, Chopp M: Bone marrow stromal cells upregulate expression of bone morphogenetic proteins 2 and 4, gap junction protein connexin-43 and synaptophysin after stroke in rats. Neuroscience 2006;141:687–695.
92.
Ujike H, Takaki M, Kodama M, Kuroda S: Gene expression related to synaptogenesis, neuritogenesis, and MAP kinase in behavioral sensitization to psychostimulants. Ann NY Acad Sci 2002;965:55–67.
93.
Shyu WC, Lin SZ, Chiang MF, Su CY, Li H: Intracerebral peripheral blood stem cell (CD34+) implantation induces neuroplasticity by enhancing β1 integrin-mediated angiogenesis in chronic stroke rats. J Neurosci 2006;26:3444–3453.
94.
Assmus B, Schachinger V, Teupe C, Britten M, Lehmann R, Dobert N, Grunwald F, Aicher A, Urbich C, Martin H, Hoelzer D, Dimmeler S, Zeiher AM: Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation 2002;106:3009–3017.
95.
Schachinger V, Assmus B, Britten MB, Ho-nold J, Lehmann R, Teupe C, Abolmaali ND, Vogl TJ, Hofmann WK, Martin H, Dimme-ler S, Zeiher AM: Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI trial. J Am Coll Cardiol 2004;44:1690–1699.
96.
Numaguchi Y, Sone T, Okumura K, Ishii M, Morita Y, Kubota R, Yokouchi K, Imai H, Harada M, Osanai H, Kondo T, Murohara T: The impact of the capability of circulating progenitor cell to differentiate on myocardial salvage in patients with primary acute myocardial infarction. Circulation 2006;114:I114–I119.
97.
Tse HF, Kwong YL, Chan JK, Lo G, Ho CL, Lau CP: Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation. Lancet 2003;361:47–49.
98.
Tateishi-Yuyama E, Matsubara H, Murohara T, Ikeda U, Shintani S, Masaki H, Amano K, Kishimoto Y, Yoshimoto K, Akashi H, Shimada K, Iwasaka T, Imaizumi T; Therapeutic Angiogenesis Using Cell Transplantation (TACT) Study Investigators: Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone marrow cells: a pilot study and a randomised controlled trial. Lancet 2002;360:427–435.
99.
Bang OY, Lee JS, Lee PH, Lee G: Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol 2005;57:874–882.
100.
Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzerbichler B, Schatteman G, Isner JM: Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997;275:964–967.
101.
Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, Kearne M, Magner M, Isner JM: Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 1999;85:221–228.
102.
Kerbel Q, Folkman J: Clinical translation of angiogenesis inhibitors. Nat Rev Cancer 2002;2:727–739.
103.
Schaper W, Scholz D: Factors regulating arteriogenesis. Arterioscler Thromb Vasc Biol 2003;23:1143–1151.
104.
Werner N, Nickenig G: Clinical and therapeutical implications of EPC biology in atherosclerosis. J Cell Mol Med 2006;10:318–332.
105.
Urbich C, Dimmeler S: Endothelial progenitor cells. Characterization and role in vascular biology. Circ Res 2004;95:343–353.
106.
Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, Hackett NR, Crystal RG, Besmer P, Lyden D, Moore MA, Werb Z, Rafii S: Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 2002;109:625–637.
107.
Shintani S, Murohara T, Ikeda H, Ueno T, Honma T, Katoh A, Sasaki K, Shimada T, Oike Y, Imaizumi T: Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation 2001;103:2776–2779.
108.
Gill M, Dias S, Hattori K, Rivera ML, Hicklin D, Witte L, Girardi L, Yurt R, Himel H, Rafii S: Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC-133(+) endothelial precursor cells. Circ Res 2001;88:167–174.
109.
Yamaguchi J, Kusano KF, Masuo O, Kawamoto A, Silver M, Murasawa S, Bosch-Marce M, Masuda H, Losordo DW, Isner JM, Asahara T: Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization. Circulation 2003;107:1322–1328.
110.
Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, Magner M, Isner JM, Asahara T: Ischemia- and cytokine- induced mobilization of bone marrow- derived endothelial progenitor cells for neovascularization. Nat Med 1999;5:434–438.
111.
Heeschen C, Aicher A, Lehmann R, Fichtl-scherer S, Vasa M, Urbich C, Mildner-Rihm C, Martin H, Zeiher AM, Dimmeler S: Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood 2003;102:1340–1346.
112.
Bahlmann FH, De Groot K, Spandau JM, Landry AL, Hertel B, Duckert T, Boehm SM, Menne J, Haller H, Fliser D: Erythropoietin regulates endothelial progenitor cells. Blood 2004;103:921–926.
113.
Hattori K, Dias S, Heissig B, Hackett NR, Lyden D, Tateno M, Hicklin DJ, Zhu Z, Witte L, Crystal RG, Moore MA, Rafii S: Vascular endothelial growth factor and angiopoietin-1 stimulate postnatal hematopoiesis by recruitment of vasculogenic and hematopoietic stem cells. J Exp Med 2001;193:1005–1014.
114.
Aicher A, Heeschen C, Mildner-Rihm C, Urbich C, Ihling C, Technau-Ihling K, Zeiher AM, Dimmeler S: Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells. Nat Med 2003;9:1370–1376.
115.
Laufs U, Werner N, Link A, Endres M, Wassmann S, Jurgens K, Miche E, Bohm M, Nickenig G: Physical training increases endothelial progenitor cells, inhibits neointima formation, and enhances angiogenesis. Circulation 2004;109:220–226.
116.
Iwakura A, Luedemann C, Shastry S, Hanley A, Kearney M, Aikawa R, Isner JM, Asahara T, Losordo DW: Estrogen-mediated, endothelial nitric oxide synthase- dependent mobilization of bone marrow-derived endothelial progenitor cells contributes to reendothelialization after arterial injury. Circulation 2003;108:3115– 3121.
117.
Strehlow K, Werner N, Berweiler J, Link A, Dirnagl U, Priller J, Laufs K, Ghaeni L, Milosevic M, Bohm M, Nickenig G: Estrogen increases bone marrow-derived endothelial progenitor cell production and diminishes neointima formation. Circulation 2003;107:3059–3065.
118.
Llevadot J, Murasawa S, Kureishi Y, Uchida S, Masuda H, Kawamoto A, Walsh K, Isner JM, Asahara T: HMG-CoA reductase inhibitor mobilizes bone marrow-derived endothelial progenitor cells. J Clin Invest 2001;108:399–405.
119.
Dimmeler S, Aicher A, Vasa M, Mildner-Rihm C, Adler K, Tiemann M, Rutten H, Fichtlscherer S, Martin H, Zeiher AM: HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. J Clin Invest 2001;108:391–397.
120.
Assmus B, Urbich C, Aicher A, Hofmann WK, Haendeler J, Rossig L, Spyridopoulos I, Zeiher AM, Dimmeler S: HMG-CoA reductase inhibitors reduce senescence and increase proliferation of endothelial progenitor cells via regulation of cell cycle regulatory genes. Circ Res 2003;92:1049–1055.
121.
Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, Böhm M, Nickenig G: Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 2005;353:999–1007.
122.
Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H, Zeiher AM, Dimmeler S: Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 2001;89:E1–E7.
123.
Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA, Finkel T: Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 2003;348:593–600.
124.
Chen JZ, Zhu JH, Wang XX, Zhu JH, Xie XD, Sun J, Shang YP, Guo XG, Dai HM, Hu SJ: Effects of homocysteine on number and activity of endothelial progenitor cells from peripheral blood. J Mol Cell Cardiol 2004;36:233–239.
125.
Verma S, Kuliszewski MA, Li SH, Szmitko PE, Zucco L, Wang CH, Badiwala MV, Mickle DA, Weisel RD, Fedak PW, Stewart DJ, Kutryk MJ: C-reactive protein attenuates endothelial progenitor cell survival, differentiation, and function: further evidence of a mechanistic link between C-reactive protein and cardiovascular disease. Circulation 2004;109:2058–2067.
126.
Vasa M, Fichtlscherer S, Adler K, Aicher A, Martin H, Zeiher AM, Dimmeler S: Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease. Circulation 2001;103:2885–2890.
127.
Zhang ZG, Zhang L, Jiang Q, Chopp M: Bone marrow-derived endothelial progenitor cells participate in cerebral neovascularization after focal cerebral ischemia in the adult mouse. Circ Res 2002;90:284–288.
128.
Kalka C, Masuda H, Takahashi T, Kalka-Moll WM, Silver M, Kearney M, Li T, Isner JM, Asahara T: Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci USA 2000;97:3422–3427.
129.
Kawamoto A, Gwon HC, Iwaguro H, Yamaguchi JI, Uchida S, Masuda H, Silver M, Ma H, Kearney M, Isner JM, Asahara T: Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia. Circulation 2001;103:634–637.
130.
Schmidt-Lucke C, Rossig L, Fichtlscherer S, Vasa M, Britten M, Kamper U, Dimmeler S, Zeiher AM: Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation 2005;111:2981–2987.
131.
Taguchi A, Matsuyama T, Moriwaki H, Hayashi T, Hayashida K, Nagatsuka K, Todo K, Mori K, Stern DM, Soma T, Naritomi H: Circulating CD34-positive cells provide an index of cerebrovascular function. Circulation 2004;109:2979–2982.
132.
Ghani U, Shuaib A, Salam A, Nasir A, Shu-aib U, Jeerakathil T, Sher F, O’Rourke F, Nasser AM, Schwindt B, Todd K: Endothelial progenitor cells during cerebrovascular disease. Stroke 2005;36:151–153.
133.
Sobrino T, Abella J, Lizasoain I, Blanco M, Rodríguez-Yáñez M, Moro M, Leira R, Ca-stillo J: Endothelial progenitor cells (EPCs) in the recovery of the cerebral infarction. Program No 588.2. 2005 Abstract Viewer/Itinerary Planner. Washington, Society for Neuroscience, 2005. Online.
134.
Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH: Neurogenesis in the adult human hippocampus. Nat Med 1998;4:1313–1317.
135.
Jin K, Wang X, Xie L, Mao XO, Zhu W, Wang Y, Shen J, Mao Y, Banwait S, Greenberg DA: Evidence for stroke-induced neurogenesis in the human brain. Proc Natl Acad Sci USA 2006;103:13198–13202.
136.
Parent JM, Vexler ZS, Gong C, Derugin N, Ferriero DM: Rat forebrain neurogenesis and striatal neuron replacement after focal stroke. Ann Neurol 2002;52:802–813.
137.
Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O: Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 2002;8:963–970.
138.
Jin K, Sun Y, Xie L, Peel A, Mao XO, Batteur S, Greenberg DA: Directed migration of neuronal precursors into the ischemic cerebral cortex and striatum. Mol Cell Neurosci 2003;24:171–189.
139.
Lindwall O, Kokaia Z: Recovery and rehabilitation in stroke: stem cells. Stroke 2004;35:2691–2694.
140.
Lichtenwalner RJ, Parent JM: Adult neurogenesis and the ischemic forebrain. J Cereb Blood Flow Metab 2006;26:1–20.
141.
Kokaia Z, Lindvall O: Neurogenesis after ischaemic brain insults. Curr Opin Neurobiol 2003;13:127–132.
142.
Hayashi J, Takagi Y, Fukuda H, Imazato T, Nishimura M, Fujimoto M, Takahashi J, Hashimoto N, Nozaki K: Primate embryonic stem cell-derived neuronal progenitors transplanted into ischemic brain. J Cereb Blood Flow Metab 2006;26:906–914.
143.
Hoehn M, Küstermann E, Blunk J, Wiedermann D, Trapp T, Wecker S, Föcking M, Arnold H, Hescheler J, Fleischmann BK, Schwindt W, Bührle C: Monitoring of implanted stem cell migration in vivo: a highly resolved in vivo magnetic resonance imaging investigation of experimental stroke in rat. Proc Natl Acad Sci USA 2002;99:16267–16272.
144.
Kondziolka D, Wechsler L, Goldstein S, Meltzer C, Thulborn KR, Gebel J, Jannetta P, DeCesare S, Elder EM, McGrogan M, Reitman MA, Bynum L: Transplantation of cultured human neuronal cells for patients with stroke. Neurology 2000;55:565–569.
145.
Mezey E, Chandross KJ, Harta G, Maki RA, McKercher SR: Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science 2000;290:1779–1782.
146.
Brazelton TR, Rossi FM, Keshet GI, Blau HM: From marrow to brain: expression of neuronal phenotypes in adult mice. Science 2000;290:1775–1779.
147.
Hess DC, Hill WD, Martin-Studdard A, Carroll J, Brailer J, Carothers J: Bone marrow as a source of endothelial cells and NeuN-expressing cells after stroke. Stroke 2002;33:1362–1368.
148.
Corti S, Locatelli F, Strazzer S, Salani S, Del Bo R, Soligo D, Bossolasco P, Bresolin N, Scarlato G, Comi GP: Modulated generation of neuronal cells from bone marrow by expansion and mobilization of circulating stem cells with in vivo cytokine treatment. Exp Neurol 2002;177:443–452.
149.
Mezey E, Key S, Vogelsang G, Szalayova I, Lange GD, Crain B: Transplanted bone marrow generates new neurons in human brains. Proc Natl Acad Sci USA 2003;100:1364–1369.
150.
Shyu WC, Lin SZ, Yang HI, Tzeng YS, Pang CY, Yen PS, Li H: Functional recovery of stroke rats induced by granulocyte colony-stimulating factor-stimulated stem cells. Circulation 2004;110:1847–1854.
151.
Kawada H, Takizawa S, Takanashi T, Morita Y, Fujita J, Fukuda K, Takagi S, Okano H, Ando K, Hotta T: Administration of hematopoietic cytokines in the subacute phase after cerebral infarction is effective for functional recovery facilitating proliferation of intrinsic neural stem/progenitor cells and transition of bone marrow-derived neuronal cells. Circulation 2006;113:701–710.
152.
Shyu WC, Lin SZ, Lee CC, Liu DD, Li H: Granulocyte colony-stimulating factor for acute ischemic stroke: a randomized controlled trial. CMAJ 2006;174:927–933.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.