Experimental approaches to study functional recovery following cerebral ischemia

Cellular and Molecular Life Sciences

Volumn 68, Issue 18, 2011, Pages 3007-3017

  Lipsanen, Anu ^a,b   Jolkkonen, Jukka ^a,b  

^a UNIVERSITY OF EASTERN FINLAND   (Finland)

^b Brain Research and Rehabilitation Center Neuron   (Finland)

Author keywords

Behavioral tests; Brain repair mechanisms; Cell based therapy; Recovery of function; Restorative therapies; Stroke models

Indexed keywords

ANTICOAGULANT AGENT; ENDOTHELIN 1; THROMBIN;

ANIMAL BEHAVIOR; BRAIN ISCHEMIA; CELL THERAPY; CONVALESCENCE; EXPERIMENTAL MODEL; FORELIMB; HINDLIMB; HUMAN; HYPERTHERMIA; IMMUNE DEFICIENCY; MIDDLE CEREBRAL ARTERY OCCLUSION; NONHUMAN; PHOTOTHROMBOSIS; REVIEW; SENSORIMOTOR FUNCTION; SOMATOSENSORY SYSTEM; STRESS; STROKE; TASK PERFORMANCE; THROMBOEMBOLISM; THROMBOSIS; WEIGHT REDUCTION;

ANIMALS; BRAIN ISCHEMIA; CEREBROVASCULAR DISORDERS; DISEASE MODELS, ANIMAL; ENDOTHELIN-1; PSYCHOMOTOR DISORDERS; RATS; TISSUE THERAPY;

EID: 80052264023     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-011-0733-3     Document Type: Review

References (115)

1. Donnan GA, Fisher M, Macleod M, Davis SM (2008) Stroke. Lancet 371:1612-1623
2. Sivenius J, Torppa J, Tuomilehto J, Immonen-Räihä P, Kaari-salo M, Sarti C, Kuulasmaa K, Mähönen M, Lehtonen A, Salomaa V (2009) Modelling the burden of stroke in Finland until 2030. Int J Stroke 4:340-345
3. Sivenius J, Tuomilehto J, Immonen-Räihä P, Kaarisalo M, Sarti C, Torppa J, Kuulasmaa K, Mähönen M, Lehtonen A, Salomaa V, FINSTROKE study (2004) Continuous 15-year decrease in incidence and mortality of stroke in Finland: the FINSTROKE study. Stroke 35:420-425 (Pubitemid 38174423)
4. Lees KR, Bluhmki E, von Kummer R, Brott TG, Toni D, Grotta JC, Albers GW, Kaste M, Marler JR, Hamilton SA, Tilley BC, Davis SM, Donnan GA, Hacke W; ECASS, ATLANTIS, NINDS and EPITHET rt-PA Study Group, Allen K, Mau J, Meier D, del Zoppo G, De Silva DA, Butcher KS, Parsons MW, Barber PA, Levi C, Bladin C, Byrnes G (2010) Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 375:1695-703
5. Stemer A, Lyden P (2010) Evolution of the thrombolytic treatment window for acute ischemic stroke. Curr Neurol Neurosci Rep 10:29-33
6. Jahan R, Vinuela F (2009) Treatment of acute ischemic stroke: intravenous and endovascular therapies. Expert Rev Cardiovasc Ther 7:375-387
7. O'Collins VE, Macleod MR, Donnan GA, Horky LL, van der Worp BH, Howells DW (2006) 1,026 experimental treatments in acute stroke. Ann Neurol 59:467-477 (Pubitemid 43358067)
8. Savitz SI (2007) A critical appraisal of the NXY-059 neuro-protection studies for acute stroke: a need for more rigorous testing of neuroprotective agents in animal models of stroke. Exp Neurol 205:20-25 (Pubitemid 46621180)
9. Ginsberg MD (2009) Current status of neuroprotection for cerebral ischemia: synoptic overview. Stroke 40(3 Suppl):S111-S114
10. Duncan PW, Lai SM, Keighley J (2000) Defining post-stroke recovery: implications for design and interpretation of drug trials. Neuropharmacology 39:835-841 (Pubitemid 30103686)
11. Martínez-Vila E, Irimia P (2005) Challenges of neuroprotection and neurorestoration in ischemic stroke treatment. Cerebrovasc Dis 20(Suppl 2):148-158 (Pubitemid 44689472)
12. Murphy TH, Corbett D (2009) Plasticity during stroke recovery: from synapse to behaviour. Nat Rev Neurosci 10:861-872
13. Zhang ZG, Chopp M (2009) Neurorestorative therapies for stroke: underlying mechanisms and translation to the clinic. Lancet Neurol 8:491-500
14. Dombovy ML, Bach-y-Rita P (1988) Clinical observations on recovery from stroke. Adv Neurol 47:265-276
15. Feeney D, Baron JC (1986) Diaschisis. Stroke 15:817-830 (Pubitemid 16000712)
16. Stroemer RP, Kent TA, Hulsebosch CE (1998) Enhanced neo-cortical neural sprouting, synaptogenesis, and behavioral recovery with D-amphetamine therapy after neocortical infarction in rats. Stroke 29:2381-2395 (Pubitemid 28511963)
17. Liu J, Solway K, Messing RO, Sharp FR (1998) Increased neurogenesis in the dentate gyrus after transient global ischemia in gerbils. J Neurosci 18:7768-7778 (Pubitemid 28441018)
18. Ohira K, Furuta T, Hioki H, Nakamura KC, Kuramoto E, Tanaka Y, Funatsu N, Shimizu K, Oishi T, Hayashi M, Miyakawa T, Kaneko T, Nakamura S (2009) Ischemia-induced neurogenesis of neocortical layer 1 progenitor cells. Nat Neurosci 13:173-179
19. Yu SW, Friedman B, Cheng Q, Lyden PD (2007) Stroke-evoked angiogenesis results in a transient population of microvessels. J Cereb Blood Flow Metab 27:755-763 (Pubitemid 46474610)
20. Meisel C, Schwab JM, Prass K, Meisel A, Dirnagl U (2005) Central nervous system injury-induced immune deficiency syndrome. Nat Rev Neurosci 6:775-786 (Pubitemid 41679240)
21. England T, Martin P, Bath PM (2009) Stem cells for enhancing recovery after stroke: a review. Int J Stroke 4:101-110
22. Miljan EA, Sinden JD (2009) Stem cell treatment of ischemic brain injury. Curr Opin Mol Ther 11:394-403
23. Bliss TM, Andres RH, Steinberg GK (2010) Optimizing the success of cell transplantation therapy for stroke. Neurobiol Dis 37:275-283
24. Stroke Therapy Academic Industry Roundtable (1999) Recommendations for standards regarding preclinical neuroprotective and restorative drugs. Stroke 30:2752-2758
25. Carmichael ST (2005) Rodent models of focal stroke: size, mechanism, and purpose. NeuroRx 2:396-409 (Pubitemid 41444874)
26. Braeuninger S, Kleinschnitz C (2009) Rodent models of focal cerebral ischemia: procedural pitfalls and translational problems. Exp Transl Stroke Med 1:8
27. Liu S, Zhen G, Meloni BP, Campbell K, Winn HR (2009) Rodent stroke model guidelines for preclinical stroke trials (1st edition). J Exp Stroke Transl Med 2:2-27
28. Howells DW, Porritt MJ, Rewell SS, O'Collins V, Sena ES, van der Worp HB, Traystman RJ, Macleod MR (2010) Different strokes for different folks: the rich diversity of animal models of focal cerebral ischemia. J Cereb Blood Flow Metab 30:1412-1431
29. Zanette EM, Roberti C, Mancini G, Pozzilli C, Bragoni M, Toni D (1995) Spontaneous middle cerebral artery reperfusion in ischemic stroke. A follow-up study with transcranial Doppler. Stroke 26:430-433
30. Longa EZ, Weinstein PR, Carlson S, Cummins R (1989) Reversible middle cerebral artery occlusion without craniec-tomy in rats. Stroke 20:84-91
31. Ma J, Zhao L, Nowak TS Jr (2006) Selective, reversible occlusion of the middle cerebral artery in rats by an intraluminal approach. Optimized filament design and methodology. J Neu-rosci Methods 156:76-83 (Pubitemid 44233662)
32. Hudzik TJ, Borrelli A, Bialobok P, Widzowski D, Sydserff S, Howell A, Gendron P, Corbett D, Miller J, Palmer GC (2000) Long-term functional end points following middle cerebral artery occlusion in the rat. Pharmacol Biochem Behav 65:553-562 (Pubitemid 30100689)
33. Freret T, Chazalviel L, Roussel S, Bernaudin M, Schumann-Bard P, Boulouard M (2006) Long-term functional outcome following transient middle cerebral artery occlusion in the rat: correlation between brain damage and behavioral impairment. Behav Neurosci 120:1285-1298 (Pubitemid 46058704)
34. Karhunen H, Pitkänen A, Virtanen T, Gureviciene I, Pussinen R, Ylinen A, Sivenius J, Nissinen J, Jolkkonen J (2003) Long-term functional consequences of transient occlusion of the middle cerebral artery in rats: a 1 yr follow-up of the development of epileptogenesis and memory impairment in relation to sensori-motor deficits. Epilepsy Res 54:1-10 (Pubitemid 36556192)
35. Wang-Fischer Y, Divani AA, Prado R, Koetzner L (2008) Surgical models of stoke induced by intraluminal filament implantation. In: Wang-Fischer Y (ed) Manual of stroke models in rats. CRC Press, Boca Raton, pp 107-126
36. Belayev L, Alonso OF, Busto R, Zhao W, Ginsberg MD (1996) Middle cerebral artery occlusion in the rat by intraluminal suture. Neurological and pathological evaluation of an improved model. Stroke 27:1616-1622
37. Lourbopoulos A, Karacostas D, Artemis N, Milonas I, Grigor-iadis N (2008) Effectiveness of a new modified intraluminal suture for temporary middle cerebral artery occlusion in rats of various weight. J Neurosci Methods 173:225-234
38. Sharkey J, Ritchie IM, Kelly PA (1993) Perivascular microap-plication of endothelin-1: a new model of focal cerebral ischaemia in the rat. J Cereb Blood Flow Metab 13:865-871 (Pubitemid 23244756)
39. Windle V, Szymanska A, Granter-Button S, White C, Buist R, Peeling J, Corbett D (2006) An analysis of four different methods of producing focal cerebral ischemia with endothelin-1 in the rat. Exp Neurol 201:324-334 (Pubitemid 44344225)
40. Biernaskie J, Chernenko G, Corbett D (2004) Efficacy of rehabilitative experience declines with time after focal ischemic brain injury. J Neurosci 24:1245-1254 (Pubitemid 38177031)
41. Hicks AU, Hewlett K, Windle V, Chernenko G, Ploughman M, Jolkkonen J, Weiss S, Corbett D (2007) Enriched environment enhances transplanted subventricular zone stem cell migration and functional recovery after stroke. Neuroscience 146:31-40 (Pubitemid 46654609)
42. Fuxe K, Bjelke B, Andbjer B, Grahn H, Rimondini R, Agnati LF (1997) Endothelin-1 induced lesions of the frontoparietal cortex of the rat. A possible model of focal cortical ischemia. Neuro-report 8:2623-2629
43. Adkins DL, Voorhies AC, Jones TA (2004) Behavioral and neuroplastic effects of focal endothelin-1 induced sensorimotor cortex lesions. Neuroscience 128:473-486 (Pubitemid 39294571)
44. Tamura A, Graham DI, McCulloch J, Teasdale GM (1981) Focal cerebral ischaemia in the rat: 1. Description of technique and early neuropathological consequences following middle cerebral artery occlusion. J Cereb Blood Flow Metab 1:53-60 (Pubitemid 12230166)
45. 2-adrenoceptor antagonist, atipamezole, in limb-placing task and skilled forepaw use following experimental stroke. Restor Neurol Neurosci 18:143-151 (Pubitemid 34258567)
46. Roof RL, Schielke GP, Ren X, Hall ED (2001) A comparison of long-term functional outcome after 2 middle cerebral artery occlusion models in rats. Stroke 32:2648-2657 (Pubitemid 33055320)
47. 2? channel blocker NS-7. II. Effect on the cerebral infarction, behavioral and cognitive impairments at the chronic stage of permanent middle cerebral artery occlusion in rats. Brain Res 890:170-176
48. Chen ST, Hsu CY, Hogan EL, Maricq H, Balentine JD (1986) A model of focal ischemic stroke in the rat: reproducible extensive cortical infarction. Stroke 17:738-743 (Pubitemid 16066549)
49. Zhao LR, Duan WM, Reyes M, Keene CD, Verfaillie CM, Low WC (2002) Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats. Exp Neurol 174:11-20 (Pubitemid 34218904)
50. Hicks AU, Lappalainen RS, Narkilahti S, Suuronen R, Corbett D, Sivenius J, Hovatta O, Jolkkonen J (2009) Transplantation of human embryonic stem cell (hESC)-derived neural precursor cells and enriched environment after cortical stroke in rats: cell survival and functional recovery. Eur J Neurosci 29:562-572
51. Bliss TM, Kelly S, Shah AK, Foo WC, Kohli P, Stokes C, Sun GH, Ma M, Masel J, Kleppner SR, Schallert T, Palmer T, Steinberg GK (2006) Transplantation of hNT neurons into the ischemic cortex: cell survival and effect on sensorimotor behavior. J Neurosci Res 83:1004-1014
52. Watson BD (1998) Animal modes of photochemically induced brain ischemia and stroke. In: Ginsberg MD, Bogousslavsky J (eds) Cerebrovascular disease. Pathophysiology, diagnosis, and management, vol 1. Blackwell Science, Malden M, pp 52-74
53. Watson BD, Dietrich WD, Busto R, Wachtel MS, Ginsberg MD (1985) Induction of reproducible brain infarction by photo-chemically initiated thrombosis. Ann Neurol 17:497-504 (Pubitemid 15019990)
54. Wester P, Watson BD, Prado R, Dietrich WD (1995) A photo-thrombotic 'ring' model of rat stroke-in-evolution displaying putative penumbral inversion. Stroke 26:444-450
55. Yao H, Sugimori H, Fukuda K, Takada J, Ooboshi H, Kitazono T, Ibayashi S, Iida M (2003) Photothrombotic middle cerebral artery occlusion and reperfusion laser system in spontaneously hypertensive rats. Stroke 34:2716-2721 (Pubitemid 37392773)
56. Verlooy J, Van Reempts J, Peersman G, Van de Vyver F, Van Deuren B, Borgers M, Selosse P (1993) Photochemically-induced cerebral infarction in the rat: comparison of NMR imaging and histologic changes. Acta Neurochir (Wien) 122:250-256 (Pubitemid 23219673)
57. Jolkkonen J, Jokivarsi K, Laitinen K, Gröhn O (2007) Subacute hemorrhage and resolution of edema in Rose Bengal stroke model in rats coincides with improved sensorimotor functions. Neurosci Lett 428:99-102 (Pubitemid 350051171)
58. Miyake K, Takeo S, Kaijihara H (1993) Sustained decrease in brain regional blood flow after microsphere embolism in rats. Stroke 24:415-420 (Pubitemid 23070049)
59. Walberer M, Rueger MA, Simard ML, Emig B, Jander S, Fink GR, Schroeter M (2010) Dynamics of neuroinflammation in the macrosphere model of arterio-arterial embolic focal ischemia: an approximation to human stroke patterns. Exp Transl Stroke Med 2:22
60. Zhang RL, Chopp M, Zhang ZG, Jiang Q, Ewing JR (1997) A rat model of focal embolic cerebral ischemia. Brain Res 766:83-92 (Pubitemid 27431437)
61. Orset C, Macrez R, Young AR, Panthou D, Angles-Cano E, Maubert E, Agin V, Vivien D (2007) Mouse model of in situ thromboembolic stroke and reperfusion. Stroke 38:2771-2778 (Pubitemid 47494017)
62. Gerriets T, Stolz E, Walberer M, Müller C, Rottger C, Kluge A, Kaps M, Fisher M, Bachmann G (2004) Complications and pitfalls in rat stroke models for middle cerebral artery occlusion: a comparison between the suture and the macrosphere model using magnetic resonance angiography. Stroke 35:2372-2377 (Pubitemid 39311266)
63. Herz RC, Jonker M, Verheul HB, Hillen B, Versteeg DH, de Wildt DJ (1996) Middle cerebral artery occlusion in Wistar and Fischer-344 rats: functional and morphological assessment of the model. J Cereb Blood Flow Metab 16:296-302
64. Duverger D, MacKenzie ET (1988) The quantification of cerebral infarction following focal ischemia in the rat: influence of strain, arterial pressure, blood glucose concentration, and age. J Cereb Blood Flow Metab 8:449-461
65. Sauter A, Rudin M (1995) Strain-dependent drug effects in rat middle cerebral artery occlusion model of stroke. J Pharmacol Exp Ther 274:1008-1013
66. Wang LC, Futrell N, Wang DZ, Chen FJ, Zhai QH, Schultz LR (1995) A reproducible model of middle cerebral infarcts compatible with long-term survival, in aged rats. Stroke 26:2087-2090
67. Wang RY, Wang PS, Yang YR (2003) Effect of age in rats following middle cerebral artery occlusion. Gerontology 49:27-32 (Pubitemid 35398577)
68. Dittmar MS, Fehm NP, Vatankhah B, Bogdahn U, Schlachetzki F (2005) Adverse effects of the intraluminal filament model of middle cerebral artery occlusion. Stroke 36:530-532 (Pubitemid 40344150)
69. Virtanen T, Jolkkonen J, Sivenius J (2004) Re: external carotid artery territory ischemia impairs outcome in the endovascular filament model of middle cerebral artery occlusion in rats. Stroke 35:e9-e10 author reply e9-e10
70. Erdo F, Berzsenyi P, Német L, Andrási F (2006) Talampanel improves the functional deficit after transient focal cerebral ischemia in rats. A 30 day follow up study. Brain Res Bull 68:269-276 (Pubitemid 41827730)
71. Morikawa E, Ginsberg MD, Dietrich WD, Duncan RC, Kray-dieh S, Globus MY, Busto R (1992) The significance of brain temperature in focal cerebral ischemia: histopathological consequences of middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 12:380-389
72. Zhao Q, Memezawa H, Smith ML, Siesjö BK (1994) Hyper-thermia complicates middle cerebral artery occlusion induced by an intraluminal filament. Brain Res 649:253-259 (Pubitemid 24197219)
73. Liesz A, Hagmann S, Zschoche C, Adamek J, Zhou W, Sun L, Hug A, Zorn M, Dalpke A, Nawroth P, Veltkamp R (2009) The spectrum of systemic immune alterations after murine focal ischemia: immunodepression versus immunomodulation. Stroke 40:2849-2858
74. Kumar S, Selim MH, Caplan LR (2010) Medical complications after stroke. Lancet Neurol 9:105-118
75. Kirkland SW, Coma AK, Colwell KL, Metz GA (2008) Delayed recovery and exaggerated infarct size by post-lesion stress in a rat model of focal cerebral stroke. Brain Res 1201:151-160
76. Li F, Omae T, Fisher M (1999) Spontaneous hyperthermia and its mechanism in the intraluminal suture middle cerebral artery occlusion model of rats. Stroke 30:2464-2470
77. Reglodi D, Somogyvari-Vigh A, Maderdrut JL, Vigh S, Arimura A (2000) Postischemic spontaneous hyperthermia and its effects in middle cerebral artery occlusion in the rat. Exp Neurol 163:399-407 (Pubitemid 30399089)
78. MacLellan CL, Colbourne F (2005) Mild to moderate hyper-thermia does not worsen outcome after severe intracerebral hemorrhage in rats. J Cereb Blood Flow Metab 25:1020-1029 (Pubitemid 41061717)
79. Meisel C, Prass K, Braun J, Victorov I, Wolf T, Megow D, Halle E, Volk HD, Dirnagl U, Meisel A (2004) Preventive antibacterial treatment improves the general medical and neurological outcome in a mouse model of stroke. Stroke 35:2-6 (Pubitemid 38057579)
80. Langdon KD, Maclellan CL, Corbett D (2010) Prolonged, 24 h delayed peripheral inflammation increases short-and long-term functional impairment and histopathological damage after focal ischemia in the rat. J Cereb Blood Flow Metab 30:1450-1459
81. Engel O, Dirnagl U, Meisel A (2010) Infection-an amendment to the stroke model guidelines. J Exp Stroke Transl Med 3:29-32
82. Hunter AJ, Hatcher J, Virley D, Nelson P, Irving E, Hadingham SJ, Parsons AA (2000) Functional assessments in mice and rats after focal stroke. Neuropharmacology 39:806-816 (Pubitemid 30103684)
83. Schallert T, Fleming SM, Leasure JL, Tillerson JL, Bland ST (2000) CNS plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke, cortical ablation, parkinsonism and spinal cord injury. Neuropharmacology 39:777-787 (Pubitemid 30103682)
84. Schallert T (2006) Behavioral tests for preclinical intervention assessment. NeuroRx 3:497-504 (Pubitemid 44443020)
85. Kleim JA, Boychuk JA, Adkins DL (2007) Rat models of upper extremity impairment in stroke. ILAR J 48:374-384 (Pubitemid 350194369)
86. Modo M (2009) Long-term survival and serial assessment of stroke damage and recovery-practical and methodological considerations. J Exp Stroke Trans Med 2:52-68
87. Schaar KL, Brenneman MM, Savitz SI (2010) Functional assessments in the rodent stroke model. Exp Transl Stroke Med 2:13
88. Savitz SI, Chopp M, Deans R, Carmichael ST, Phinney D, Wechsler L (2011) Stem cell therapy as an emerging paradigm for stroke (STEPS) II. Stroke 42:825-829
89. Chen J, Li Y, Wang L, Zhang Z, Lu D, Lu M, Chopp M (2001) Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 32:1005-1011 (Pubitemid 32285175)
90. Boltze J, Kowalski I, Förschler A, Schmidt U, Wagner D, Lobsien D, Emmrich J, Egger D, Kamprad M, Blunk J, Emm-rich F (2006) The stairway: a novel behavioral test detecting sensomotoric stroke deficits in rats. Artif Organs 30:756-763 (Pubitemid 44521366)
91. De Ryck M, Van Reempts J, Duytschaever H, Van Deuren B, Clincke G (1992) Neocortical localization of tactile/proprio-ceptive limb placing reactions in the rat. Brain Res 573:44-60
92. 2- adrenoceptor antagonist, atipamezole, after focal cerebral ischemia in rats. Eur J Pharmacol 400:211-219 (Pubitemid 30438729)
93. Mäkinen S, Kekarainen T, Nystedt J, Liimatainen T, Huhtala T, Närvänen A, Laine J, Jolkkonen J (2006) Human umbilical cord blood cells do not improve sensorimotor or cognitive outcome following transient middle cerebral artery occlusion in rats. Brain Res 1123:207-215
94. Hamm RJ, Pike BR, O'Dell DM, Lyeth BG, Jenkins LW (1994) The rotarod test: an evaluation of its effectiveness in assessing motor deficits following traumatic brain injury. J Neurotrauma 11:187-196 (Pubitemid 24174507)
95. Modo M, Stroemer RP, Tang E, Veizovic T, Sowniski P, Hodges H (2000) Neurological sequelae and long-term behavioural assessment of rats with transient middle cerebral artery occlusion. J Neurosci Methods 104:99-109 (Pubitemid 32040900)
96. Schallert T, Woodlee MT (2005) Orienting and placing. In: Whishaw IQ, Kolb B (eds) The behavior of the laboratory rat. A handbook with tests. Oxford University Press, New York, pp 129-140
97. 2-adrenoceptor antagonist. Pharmacol Biochem Behav 74:663-669 (Pubitemid 36126545)
98. Montoya CP, Campbell-Hope LJ, Pemberton KD, Dunnett SB (1991) The ''staircase test'': a measure of independent forelimb reaching and grasping abilities in rats. J Neurosci Meth 36:219-228
99. Whishaw IQ, O'Connor WT, Dunnett SB (1986) The contributions of motor cortex, nigrostriatal dopamine and caudate-putamen to skilled forelimb use in the rat. Brain 109:805-843 (Pubitemid 17175607)
100. Whishaw IQ, Pellis SM, Gorny BP, Pellis VC (1991) The impairments in reaching and the movements of compensation in rats with motor cortex lesions: an endpoint, videorecording, and movement notation analysis. Behav Brain Res 42:77-91
101. Metz GA, Whishaw IQ (2000) Skilled reaching an action pattern: stability in rat (Rattus norvegicus) grasping movements as a function of changing food pellet size. Behav Brain Res 116:111-122
102. van Groen T, Puurunen K, Mäki HM, Sivenius J, Jolkkonen J (2005) Transformation of diffuse beta-amyloid precursor protein and beta-amyloid deposits to plaques in the thalamus after transient occlusion of the middle cerebral artery in rats. Stroke 36:1551-1556 (Pubitemid 40967528)
103. Kelly S, Bliss TM, Shah AK, Sun GH, Ma M, Foo WC, Masel J, Yenari MA, Weissman IL, Uchida N, Palmer T, Steinberg GK (2004) Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex. Proc Natl Acad Sci USA 101:11839-11844 (Pubitemid 39095381)
104. Guzman R, Choi R, Gera A, De Los Angeles A, Andres RH, Steinberg GK (2008) Intravascular cell replacement therapy for stroke. Neurosurg Focus 24:E15
105. Hicks A, Jolkkonen J (2009) Challenges and possibilities of intravascular cell therapy in stroke. Acta Neurobiol Exp (Wars) 69:1-11
106. Janowski M, Walczak P, Date I (2010) Intravenous route of cell delivery for treatment of neurological disorders: a meta-analysis of preclinical results. Stem Cells Dev 19:5-16
107. Chua JY, Pendharkar AV, Wang N, Choi R, Andres RH, Gaeta X, Zhang J, Moseley ME, Guzman R (2011) Intra-arterial injection of neural stem cells using a microneedle technique does not cause microembolic strokes. J Cereb Blood Flow Metab 31:1263-1271
108. Borlongan CV, Hadman M, Sanberg CD, Sanberg PR (2004) Central nervous system entry of peripherally injected umbilical cord blood cells is not required for neuroprotection in stroke. Stroke 35:2385-2389 (Pubitemid 39311268)
109. Vendrame M, Gemma C, Pennypacker KR, Bickford PC, Davis Sanberg C, Sanberg PR, Willing AE (2006) Cord blood rescues stroke-induced changes in splenocyte phenotype and function. Exp Neurol 199:191-200 (Pubitemid 43949266)
110. Ajmo CT Jr, Vernon DO, Collier L, Hall AA, Garbuzova-Davis S, Willing A, Pennypacker KR (2008) The spleen contributes to stroke-induced neurodegeneration. J Neurosci Res 86:2227-2234
111. Erdö F, Bührle C, Blunk J, Hoehn M, Xia Y, Fleischmann B, Föcking M, Küstermann E, Kolossov E, Hescheler J, Hossmann KA, Trapp T (2003) Host-dependent tumorigenesis of embryonic stem cell transplantation in experimental stroke. J Cereb Blood Flow Metab 23:780-785 (Pubitemid 36818686)
112. Kozłowska H, Jabłonka J, Janowski M, Jurga M, Kossut M, Domańska-Janik K (2007) Transplantation of a novel human cord blood-derived neural-like stem cell line in a rat model of cortical infarct. Stem Cells Dev 16:481-488 (Pubitemid 47016233)
113. Kawai H, Yamashita T, Ohta Y, Deguchi K, Nagotani S, Zhang X, Ikeda Y, Matsuura T, Abe K (2010) Tridermal tumorigenesis of induced pluripotent stem cells transplanted in ischemic brain. J Cereb Blood Flow Metab 30:1487-1493
114. Hicks A, Schallert T, Jolkkonen J (2009) Cell-based therapies and functional outcome in experimental stroke. Cell Stem Cell 5:139-140
115. Dirnagl U, Klehmet J, Braun JS, Harms H, Meisel C, Ziemssen T, Prass K, Meisel A (2007) Stroke-induced immunodepression: experimental evidence and clinical relevance. Stroke 38(2 Suppl): 770-773 (Pubitemid 46184257)