Cyclin-dependent kinases and stroke

Expert Opinion on Therapeutic Targets

Volumn 5, Issue 5, 2001, Pages 557-567

  Wang, Fuhu ^a   O'Hare, Michael J ^a   Park, David S ^a  

^a UNIVERSITY OF OTTAWA   (Canada)

Author keywords

Apoptosis; Cyclin dependent kinases; E2F; Excitotoxic; Ischaemia; Neuronal death; Retinoblastoma; Stroke

Indexed keywords

EID: 0141780663     PISSN: 14728222     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728222.5.5.557     Document Type: Review

References (124)

1. BARBER PA, ZHANG J, DEMCHUK AM, HILL MD, BUCHAN AM: Why are stroke patients excluded from TPA therapy? An analysis of patient eligibility. Neurology (2001) 56(8):1015-1020.
2. DEMCHUK AM, TANNE D, HILL MD et al.: Predictors of good outcome after intravenous tPA for acute ischemic stroke. Neurology (2001) 57(3):474-480.
3. PULSINELLI WA, BRIERLEY JB, PLUM F: Temporal profile of neuronal damage in a model of transient forebrain ischemia. Ann. Neurol. (1982) 11(5):491-498.
4. NEDERGAARD M, GJEDDE A, DIEMER NH: Focal ischemia of the rat brain: autoradiographic determination of cerebral glucose utilization, glucose content, and blood flow. J. Cereb. Blood Flow Metab. (1986) 6(4):414-424.
5. CHOI DW: Glutamate neurotoxicity and diseases of the nervous system. Neuron (1988) 1(8):623-634.
6. SIESJO BK: Pathophysiology and treatment of focal cerebral ischemia. Part II: mechanisms of damage and treatment. J. Neurosurg. (1992) 77(3):337-354.
7. SIESJO BK: Pathophysiology and treatment of focal cerebral ischemia. Part I: pathophysiology. J. Neurosurg. (1992) 77(2):169-184.
8. SZATKOWSKI M, ATTWELL D: Triggering and execution of neuronal death in brain ischaemia: two phases of glutamate release by different mechanisms. Trends Neurosci. (1994) 17(9):359-365.
9. DIRNAGL U, IADECOLA C, MOSKOWITZ MA: Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci. (1999) 22(9):391-397.
10. GRAHAM SH, CHEN J: Programmed cell death in cerebral ischemia. J. Cereb. Blood Flow Metab. (2001) 21(2):99-109.
11. MAJNO G, JORIS I: Apoptosis, oncosis, and necrosis. An overview of cell death. Am. J. Pathol. (1995) 146(1):3-15.
12. YAMASHIMA T: Implication of cysteine proteases calpain, cathepsin and caspase in ischemic neuronal death of primates. Prog. Neurobiol. (2000) 62(3):273-295.
13. FISKUM G: Mitochondrial participation in ischemic and traumatic neural cell death. J. Neurotrauma (2000) 17(10):843-855.
14. LEWEN A, MATZ P, CHAN PH: Free radical pathways in CNS injury. J. Neurotrauma (2000) 17(10):871-890.
15. ZHANG J, SNYDER SH: Nitric oxide in the nervous system. Annu. Rev. Pharmacol. Toxicol. (1995) 35:213-233.
16. DAWSON VL, DAWSON TM: Nitric oxide in neurodegeneration. Prog. Brain Res. (1998) 118:215-229.
17. ELIASSON MJ, HUANG Z, FERRANTE RJ et al.: Neuronal nitric oxide synthase activation and peroxynitrite formation in ischemic stroke linked to neural damage. J. Neurosci. (1999) 19(14):5910-5918.
18. HADLEY MN, ZABRAMSKI JM, SPETZLER RF, RIGAMONTI D, FIFIELD MS, JOHNSON PC: The efficacy of intravenous nimodipine in the treatment of focal cerebral ischemia in a primate model. Neurosurgery (1989) 25(1):63-70.
19. FOGELHOLM R, ERILA T, PALOMAKI H, MURROS K, KASTE M: Effect of nimodipine on final infarct volume after acute ischemic stroke. Cerebrovasc. Dis. (2000) 10(3):189-193.
20. BOGAERT L, O'NEILL MJ, MOONEN J et al.: The effects of LY393613, nimodipine and verapamil, in focal cerebral ischaemia. Eur. J. Pharmacol. (2001) 411(1-2):71-83.
21. BUCHAN A, LI H, PULSINELLI WA: The N-methyl-D-aspartate antagonist, MK-801, fails to protect against neuronal damage caused by transient, severe forebrain ischemia in adult rats. J. Neurosci. (1991) 11(4):1049-1056.
22. BUCHAN AM, XUE D, HUANG ZG, SMITH KH, LESIUK H: Delayed AMPA receptor blockade reduces cerebral infarction induced by focal ischemia. Neuroreport (1991) 2(8):473-476.
23. LEES KR, ASPLUND K, CAROLEI A et al.: Glycine antagonist (gavestinel) in neuroprotection (GAIN International) in patients with acute stroke: a randomised controlled trial. GAIN International Investigators. Lancet (2000) 355(9219):1949-1954.
24. MACMANUS JP, FLISS H, PRESTON E, RASQUINHA I, TUOR U: Cerebral ischemia produces laddered DNA fragments distinct from cardiac ischemia and archetypal apoptosis. J. Cereb. Blood Flow Metab. (1999) 19(5):502-510.
25. MACMANUS JP, BUCHAN AM: Apoptosis after experimental stroke: fact or fashion? J. Neurotrauma (2000) 17(10):899-914.
26. COLBOURNE F, SUTHERLAND GR, AUER RN: Electron microscopic evidence against apoptosis as the mechanism of neuronal death in global ischemia. J. Neurosci. (1999) 19(11):4200-4210.
27. HOU S, TU Y, BUCHAN A et al.: Increases in DNA lesions and the DNA damage indicator Gadd45 following transient cerebral ischemia. Biochem. Cell Biol. (1997) 75(4):383-392.
28. IADECOLA C, ALEXANDER M: Cerebral ischemia and inflammation. Curr. Opin. Neurol. (2001) 14(1):89-94.
29. STYS PK: Anoxic and ischemic injury of myelinated axons in CNS white matter: from mechanistic concepts to therapeutics. J. Cereb. Blood Flow Metab. (1998) 18(1):2-25.
30. KERR JF, WYLLIE AH, CURRIE AR: Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer (1972) 26(4):239-257.
31. OPPENHEIM RW: Cell death during development of the nervous system. Annu. Rev. Neurosci. (1991) 14:453-501.
32. HENDERSON CE: Programmed cell death in the developing nervous system. Neuron (1996) 17(4):579-585.
33. SONG Z, STELLER H: Death by design: mechanism and control of apoptosis. Trends Cell Biol. (1999) 9(12):M49-M52.
34. NAGATA S: Apoptosis by death factor. Cell (1997) 88(3):355-365.
35. ASHKENAZI A, DIXIT VM: Death receptors: signaling and modulation. Science (1998) 281(5381):1305-1308.
36. THORNBERRY NA, LAZEBNIK Y: Caspases: enemies within. Science (1998) 281(5381):1312-1316.
37. GREEN DR, REED JC: Mitochondria and apoptosis. Science (1998) 281(5381):1309-1312.
38. LI H, ZHU H, XU CJ, YUAN J: Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell (1998) 94(4):491-501.
39. CRUMRINE RC, THOMAS AL, MORGAN PF: Attenuation of p53 expression protects against focal ischemic damage in transgenic mice. J. Cereb. Blood Flow Metab. (1994) 14(6):887-891.
40. LI Y, CHOPP M, ZHANG ZG, ZALOGA C, NIEWENHUIS L, GAUTAM S: p53-immunoreactive protein and p53 mRNA expression after transient middle cerebral artery occlusion in rats. Stroke (1994) 25(4):849-855; discussion 855-846.
41. MCGAHAN L, HAKIM AM, ROBERTSON GS: Hippocampal Myc and p53 expression following transient global ischemia. Brain Res. Mol. Brain Res. (1998) 56(1-2):133-145.
42. MORRISON RS, KINOSHITA Y: The role of p53 in neuronal cell death. Cell Death Differ. (2000) 7(10):868-879.
43. CULMSEE C, ZHU X, YU QS et al.: A synthetic inhibitor of p53 protects neurons against death induced by ischemic and excitotoxic insults, and amyloid beta-peptide. J. Neurochem. (2001) 77(1):220-228.
44. 2terminal kinase and p38 mitogen-activated protein kinase after transient forebrain ischemia in mice. Neurosci. Lett. (2000) 294(2):117-120.
45. WU DC, YE W, CHE XM, YANG GY: Activation of mitogen-activated protein kinases after permanent cerebral artery occlusion in mouse brain. J. Cereb. Blood Flow Metab. (2000) 20(9):1320-1330.
46. SCHNEIDER A, MARTIN-VILLALBA A, WEIH F, VOGEL J, WIRTH T, SCHWANINGER M: NF-κB is activated and promotes cell death in focal cerebral ischemia. Nature Med. (1999) 5(5):554-559.
47. YU Z, ZHOU D, BRUCE-KELLER AJ, KINDY MS, MATTSON MP: Lack of the p50 subunit of nuclear factor-κB increases the vulnerability of hippocampal neurons to exchotoxic injury. J. Neurosci. (1999) 19(20):8856-8865.
48. MATTSON MP, CULMSEE C, YU Z, CAMANDOLA S: Roles of nuclear factor κB in neuronal survival and plasticity. J. Neurochem. (2000) 74(2):443-456.
49. NOGAWA S, ZHANG F, ROSS ME, IADECOLA C: Cyclo-oxygenase-2 gene expression in neurons contributes to ischemic brain damage. J. Neurosci. (1997) 17(8):2746-2755.
50. SAIRANEN T, RISTIMAKI A, KARJALAINEN-LINDSBERG ML, PAETAU A, KASTE M, LINDSBERG PJ: Cyclooxygenase-2 is induced globally in infarcted human brain. Ann. Neurol. (1998) 43(6):738-747.
51. NAGAYAMA M, NIWA K, NAGAYAMA T, ROSS ME, IADECOLA C: The cyclooxygenase-2 inhibitor NS-398 ameliorates ischemic brain injury in wild-type mice but not in mice with deletion of the inducible nitric oxide synthase gene. J. Cereb. Blood Flow Metab. (1999) 19(11):I213-1219.
52. ELIASSON MJ, SAMPEI K, MANDIR AS et al.: Poly(ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischemia. Nature Med. (1997) 3(10):1089-1095.
53. ENDRES M, WANG ZQ, NAMURA S, WAEBER C, MOSKOWITZ MA: Ischemic brain injury is mediated by the activation of poly(ADP-ribose)polymerase. J. Cereb. Blood Flow Metab. (1997) 17(11):1143-1151.
54. NAGY Z: Cell cycle regulatory failure in neurones: causes and consequences. Neurobiol. Aging (2000) 21(6):761-769.
55. COPANI A, ANGELA SORTING M, NICOLETTI F, BRUNO V, UBERTIA D, MEMO M: Activation of cell cycle-associated proteins in neuronal death: a mandatory or dispensable path? Trends Neurosci. (2001) 24(1):25-31.
56. GUO M, HAY BA: Cell proliferation and apoptosis. Curr. Opn. Cell Biol. (1999) 11(6):745-752.
57. LUNDBERG AS, WEINBERG RA: Control of the cell cycle and apoptosis. Eur. J. Cancer (1999) 35(4):531-539.
58. VOGELSTEIN B, LANE D, LEVINE AJ: Surfing the p53 network. Nature (2000) 408(6810):307-310.
59. VOUSDEN KH: p53: death star. Cell (2000) 103(5):691-694.
60. PINES J: Cyclins and their associated cyclin-dependent kinases in the human cell cycle. Biochem. Soc. Trans. (1993) 21(4):921-925.
61. PINES J: Cyclins and cyclin-dependent kinases: take your partners. Trends Biochem. Sci. (1993) 18(6):195-197.
62. 1 cyclin-dependent kinases in the mammalian cell cycle. Curr. Opin. Cell Biol. (2000) 12(6):676-684.
63. PINES J: Cyclins and cyclin-dependent kinases: a biochemical view. Biochem. J. (1995)308(3):697-711.
64. MORGAN DO: Principles of CDK regulation. Nature (1995) 374(6518):131-134.
65. 1-phase progression. Genes Dev. (1999) 13(12):1501-1512.
66. DYSON N: The regulation of E2F by pRb-family proteins. Genes Dev. (1998) 12(15):2245-2262.
67. JACKS T, FAZELI A, SCHMITT EM, BRONSON RT, GOODELL MA, WEINBERG RA: Effects of an Rb mutation in the mouse. Nature (1992) 359(6393):295-300.
68. CLARKE AR, MAANDAG ER, VAN ROON M et al.: Requirement for a functional Rb-1 gene in murine development. Nature (1992) 359(6393):328-330.
69. LEE EY, CHANG CY, HU N et al.: Mice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesis. Nature (1992) 359(6393):288-294.
70. LEE EY, HU N, YUAN SS et al.: Dual roles of the retinoblastoma protein in cell cycle regulation and neuron differentiation. Genes Dev. (1994) 8(17):2008-2021.
71. FEDDERSEN RM, EHLENFELDT R, YUNIS WS, CLARK HB, ORR HT: Disrupted cerebellar cortical development and progressive degeneration of Purkinje cells in SV40 T antigen transgenic mice. Neuron (1992) 9(5):955-966.
72. FEDDERSEN RM, CLARK HB, YUNIS WS, ORR HT: In vivo viability of postmitotic Purkinje neurons requires pRb family member function. Mol. Cell. Neurosci. (1995) 6(2):153-167.
73. 1 during programmed cell death. Neuron (1994) 12(2):343-355.
74. GAO CY, ZELENKA PS: Induction of cyclin B and H1 kinase activity in apoptotic PC12 cells. Exp. Cell Res. (1995) 219(2):612-618.
75. PARK DS, MORRIS EJ, PADMANABHAN J, SHELANSKI ML, GELLER HM, GREENE LA: Cyclin-dependent kinases participate in death of neurons evoked by DNA- damaging agents. J. Cell Biol. (1998) 143(2):457-467.
76. GIOVANNI A, WIRTZ-BRUGGER F, KERAMARIS E, SLACK R, PARK DS: Involvement of cell cycle elements, cyclin-dependent kinases, pRb, and E2F x DP, in β-amyloid-induced neuronal death. J. Biol. Chem. (1999) 274(27):19011-19016.
77. GILL JS, WINDEBANK AJ: Cisplatin-induced apoptosis in rat dorsal root ganglion neurons is associated with attempted entry into the cell cycle. J. Clin. Invest. (1998) 101(12):2842-2850.
78. PADMANABHAN J, PARK DS, GREENE LA, SHELANSKI ML: Role of cell cycle regulatory proteins in cerebellar granule neuron apoptosis. J. Neurosci. (1999) 19(20):8747-8756.
79. KRANENBURG O, VAN DER EB AJ, ZANTEMA A: Cyclin D1 is an essential mediator of apoptotic neuronal cell death. EMBO J. (1996) 15(1):46-54.
80. POLUHA W, SCHONHOFF CM, HARRINGTON KS et al.: A novel, nerve growth factor-activated pathway involving nitric oxide, p53, and p21 WAF1 regulates neuronal differentiation of PC12 cells. J. Biol. Chem. (1997) 272(38):24002-24007.
81. KATCHANOV J, HARMS C, GERTZ K et al.: Mild cerebral ischemia induces loss of cyclin-dependent kinase inhibitors and activation of cell cycle machinery before delayed neuronal cell death. J. Neurosci. (2001) 21(14):5045-5053.
82. PARK DS, LEVINE B, FERRARI G, GREENE LA: Cydin-dependent kinase inhibitors and dominant negative cyclin dependent kinase 4 and 6 promote survival of NGF-deprived sympathetic neurons. J. Neurosci. (1997) 17(23):8975-8983.
83. PARK DS, FARINELLI SE, GREENE LA: Inhibitors of cyclin-dependent kinases promote survival of post-mitotic neuronally differentiated PC12 cells and sympathetic neurons. J. Biol. Chem. (1996) 271(14):8161-8169.
84. MARKUS MA, KAHLE PJ, WINKLER A, HORSTMANN S, ANNESER JM, BORASIO GD: Survival-promoting activity of inhibitors of cyclin-dependent kinases on primary neurons correlates with inhibition of c-Jun kinase-1. Neurobiol. Dis. (1997) 4(2):122-133.
85. 1/S cell cycle blockers and inhibitors of cyclin-dependent kinases suppress camptothecin-induced neuronal apoptosis. J. Neurosci. (1997) 17(4):1256-1270.
86. NAGY Z, ESIRI MM, CATO AM, SMITH AD: Cell cycle markers in the hippocampus in Alzheimer's disease. Acta Neuropathol. (Berl) (1997) 94(1):6-15.
87. MCSHEA A, HARRIS PL, WEBSTER KR, WAHL AF, SMITH MA: Abnormal expression of the cell cycle regulators P16 and CDK4 in Alzheimer's disease. Am. J. Pathol. (1997) 150(6):1933-1939.
88. 1 kinase in degenerating neurons of Alzheimer's disease brain. J. Neurosci. (1997) 17(10):3588-3598.
89. BUSSER J, GELDMACHER DS, HERRUP K: Ectopic cell cycle proteins predict the sites of neuronal cell death in Alzheimer's disease brain. J. Neurosci. (1998) 18(8):2801-2807.
90. SMITH TW, LIPPA CF: Ki-67 immunoreactivity in Alzheimer's disease and other neurodegenerative disorders. J. Neuropathol. Exp. Neurol. (1995) 54(3):297-303.
91. NAGY Z, ESIRI MM: Neuronal cyclin expression in the hippocampus in temporal lobe epilepsy. Exp. Neurol. (1998) 150(2):240-247.
92. PARK DS, MORRIS EJ, BREMNER R et al.: Involvement of retinoblastoma family members and E2F/DP complexes in the death of neurons evoked by DNA damage. J. Neurosci. (2000) 20(9):3104-3114.
93. O'HARE MJ, HOU ST, MORRIS EJ et al.: Induction and modulation of cerebellar granule neuron death by E2F-1. J. Biol. Chem. (2000) 275(33):25358-25364.
94. HOU ST, CALLAGHAN D, FOURNIER MC et al.: The transcription factor E2F1 modulates apoptosis of neurons. J. Neurochem. (2000) 75(1):91-100.
95. GIOVANNI A, KERAMARIS E, MORRIS EJ et al.: E2F1 mediates death of β-amyloid-treated cortical neurons in a manner independent of p53 and dependent on Bax and caspase 3. J. Biol. Chem. (2000) 275(16):11553-11560.
96. TSAI KY, HU Y, MACLEOD KF, CROWLEY D, YAMASAKI L, JACKS T: Mutation of E2F-1 suppresses apoptosis and inappropriate S phase entry and extends survival of Rb-deficient mouse embryos. MoL Cell (1998) 2(3):293-304.
97. ZIEBOLD U, REZA T, CARON A, LEES JA: E2F3 contributes both to the inappropriate proliferation and to the apoptosis arising in Rb mutant embryos. Genes Dev. (2001) 15(4):386-391.
98. MORRIS EJ, KERAMARIS E, RIDEOUT HJ et al.: Cyclin-dependent kinases and p53 pathways are activated independently and mediate Bax activation in neurons following DNA damage. J. Neurosci. (2001) 21(14):5017-5026.
99. KERAMARIS E, STEFANIS L, MACLAURIN J et al.: Involvement of caspase 3 in apoptotic death of cortical neurons evoked by DNA damage. Mol. Cell Neurosci. (2000) 15:368-379.
100. DESAGHER S, MARTINOU JC: Mitochondria as the central control point of apoptosis. Trends Cell Biol. (2000) 10(9):369-377.
101. HOMAYOUNI R, CURRAN T: Cortical development: Cdk5 gets into sticky situations. Curr. Biol. (2000) 10(9):R331-R334.
102. PATRICK GN, ZUKERBERG L, NIKOLIC M, DE LA MONTE S, DIKKES P, TSAI LH: Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. Nature (1999) 402(6762):615-622.
103. LEE MS, KWON YT, LI M, PENG J, FRIEDLANDER RM, TSAI LH: Neurotoxicity induces cleavage of p35 to p25 by calpain. Nature (2000) 405(6784):360-364.
104. TANIGUCHI S, FUJITA Y, HAYASHI S et al.: Calpain-mediated degradation of p35 to p25 in postmortem human and rat brains. Febs. Lett. (2001) 489(1):46-50.
105. LI Y, CHOPP M, POWERS C, JIANG N: Apoptosis and protein expression after focal cerebral ischemia in rat. Brain Res. (1997) 765(2):301-312.
106. 1 proteins as mediators of neuronal death after a focal ischaemic insult. Neuroreport (1997) 8(4):1003-1007.
107. 1 in vulnerable neurons in the hippocampus after ischaemia and epilepsy: a modulator of in vivo programmed cell death? Eur. J. Neurosci. (1999) 11(1):263-278.
108. FRADE JM: Unscheduled re-entry into the cell cycle induced by NGF precedes cell death in nascent retinal neurones. J. Cell Sci. (2000) 113(Pt 7):1139-1148.
109. 1 in the adult rat brain following kainic acid treatment. Neuroreport (1996) 7(15-17):2785-2789.
110. PARK DS, OBEIDAT A, GIOVANNI A, GREENE LA: Cell cycle regulators in neuronal death evoked by excitotoxic stress: implications for neurodegeneration and its treatment. Neurobiol. Aging (2000) 21(6):771-781.
111. OSUGA H, OSUGA S, WANG F et al.: Cyclin dependent kinases as a therapeutic target for stroke. Proc. Natl. Acad. Sci. USA (2000) 97(18):10254-10259.
112. WANG F, OSUGA S, OSUGA H et al.: Cyclin dependent kinases as a therapeutic target for cerebral ischemia. Society for Neuroscience Abstract (2000) 26:1881.
113. HAYASHI T, SAKAI K, SASAKI C, ZHANG WR, ABE K: Phosphorylation of retinoblastoma protein in rat brain after transient middle cerebral artery occlusion. Neuropathol. Appl. Neurobiol. (2000) 26(4):390-397.
114. MACMANUS JP, KOCH CJ, JIAN M, WALKER T, ZURAKOWSKI B: Decreased brain infarct following focal ischemia in mice lacking the transcription factor E2F1. Neuroreport (1999) 10(13):2711-2714.
115. MORRIS MM, DYSON NJ: Retinoblastoma protein partners. Adv. Cancer Res. (2001) 82:1-54.
116. MATTSON MP, CAMANDOLA S: NF-κB in neuronal plasticity and neurodegenerative disorders. J. Clin. Invest. (2001) 107(3):247-254.
117. STEFANIS L, PARK DS, FRIEDMAN WJ, GREENE LA: Caspase-dependent and -independent death of camptothecin-treated embryonic cortical neurons. J. Neurosci. (1999) 19(15):6235-6247.
118. HARA H, FRIEDLANDER RM, GAGLIARDINI V et al.: Inhibition of interleukin-1β -converting enzyme family proteases reduces ischemic and excitotoxic neuronal damage. Proc. Natl. Acad. Sci. USA (1997) 94(5):2007-2012.
119. HARA H, FINK K, ENDRES M et al.: Attenuation of transient focal cerebral ischemic injury in transgenic mice expressing a mutant ICE inhibitory protein. J. Cereb. Blood Flow Metab. (1997) 17(4):370-375.
120. ENDRES M, NAMURA S, SHIMIZUSASAMATA M et al.: Attenuation of delayed neuronal death after mild focal ischemia in mice by inhibition of the caspase family. J. Cereb. Blood Flow Metab. (1998) 18(3):238-247.
121. SCHULZ JB, WELLER M, MOSKOWITZ MA: Caspases as treatment targets in stroke and neurodegenerative diseases. Ann. Neurol. (1999) 45(4):421-429.
122. ELDADAH BA, FADEN AI: Caspase pathways, neuronal apoptosis, and CNS injury. J. Neurotrauma (2000) 17(10):811-829.
123. COLBOURNE F, CORBETT D, ZHAO Z, YANG J, BUCHAN AM: Prolonged but delayed postischemic hypothermia: a long-term outcome study in the rat middle cerebral artery occlusion model. J. Cereb. Blood Flow Metab. (2000) 20(12):1702-1708.
124. NUDO RJ: Recovery after damage to motor cortical areas. Curr. Opin. Neurobiol. (1999) 9(6):740-747.