Role of neurotrophins in recovery of phrenic motor function following spinal cord injury.
Many individuals who sustain a cervical spinal cord injury are unable to maintain adequate ventilation due to diaphragm muscle paralysis. These patients become dependent on mechanical ventilators and this situation is associated with ongoing problems with pulmonary clearance, infections, and lung injury leading to significant morbidity and reduced life expectancy. Therefore, functional recovery of rhythmic phrenic activity and the ability to generate expulsive forces would dramatically affect the quality of life of patients with cervical spinal cord injury. Neurotrophins are very promising in that they have been shown to play an important role in modulating functional neuroplasticity. Specifically, brain-derived neurotrophic factor (BDNF) acting via the tropomyosin-related kinase receptor type B (TrkB) has been implicated in neuroplasticity following spinal cord injury. Our central hypothesis is that functional recovery of rhythmic phrenic activity after cervical spinal cord injury is enhanced by an increase in BDNF/TrkB signaling in phrenic motoneurons, providing a novel therapeutic target for patients.
Sieck
Gary C
GC
Departments of Physiology & Biomedical Engineering and Anesthesiology, Mayo Clinic, Rochester, MN 55905, United States. sieck.gary@mayo.edu
Mantilla
Carlos B
CB
D000818:Animals; D006801:Humans; D008954:Models, Biological; D009046:Motor Neurons / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D010791:Phrenic Nerve / Q000502:physiology*; D020127:Recovery of Function / Q000502:physiology*; D012119:Respiration; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
D009414:Nerve Growth Factors
Respir Care. 2006 Aug;51(8):853-68;discussion 869-70
16867197
Exp Neurol. 1981 Apr;72(1):211-25
7202624
J Comp Neurol. 2000 Dec 25;428(4):671-80
11077420
J Appl Physiol (1985). 2008 Jun;104(6):1818-27
18403452
Nature. 2005 Dec 15;438(7070):1017-21
16355225
Respir Physiol Neurobiol. 2008 Dec 10;164(1-2):252-62
18708170
Prog Brain Res. 2002;137:257-73
12440372
Exp Neurol. 2008 May;211(1):97-106
18308305
Exp Neurol. 2001 Jan;167(1):15-26
11161589
J Neurochem. 2005 May;93(3):584-94
15836617
Arch Phys Med Rehabil. 2000 Jun;81(6):757-63
10857520
J Neurosci. 2001 May 15;21(10):3457-75
11331375
J Neurosci. 1989 Jun;9(6):1910-21
2542482
Neuron. 1993 Mar;10(3):359-67
8080464
Muscle Nerve. 2004 Mar;29(3):381-6
14981737
Am J Physiol. 1949 Jun;157(3):468-76
18151754
J Neurotrauma. 2006 Jul;23(7):1137-46
16866626
J Neurosci. 2008 Feb 27;28(9):2033-42
18305238
Exp Neurol. 1997 Jan;143(1):70-81
9000447
Eur J Neurosci. 1993 Jun 1;5(6):605-13
8261135
Conf Proc IEEE Eng Med Biol Soc. 2006;2006:1204-7
17946030
J Neurotrauma. 2007 Apr;24(4):690-702
17439351
J Comp Neurol. 1989 Jun 22;284(4):519-33
2768550
Brain Res. 2008 Jun 27;1217:10-24
18511024
Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13279-86
9371837
Exp Neurol. 1984 Aug;85(2):316-35
6745377
J Neurosci. 2000 May 15;20(10):RC77
10783401
Sheng Li Xue Bao. 2003 Dec 25;55(6):617-24
14695476
J Neurotrauma. 2004 Mar;21(3):329-37
15115607
J Appl Physiol (1985). 1995 Nov;79(5):1640-9
8594024
J Neurophysiol. 1965 May;28:560-80
14328454
J Neurosci. 2001 Dec 1;21(23):9334-44
11717367
Cytokine Growth Factor Rev. 2002 Feb;13(1):11-7
11750876
Neuroscience. 2007 Apr 25;146(1):178-89
17346898
Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3555-60
11248116
J Neurosci. 2000 Jan 15;20(2):771-82
10632606
Exp Neurol. 1991 Jan;111(1):135-9
1984430
Exp Neurol. 1991 Feb;111(2):244-50
1989900
Ann N Y Acad Sci. 1999 Apr 30;868:515-25
10414328
Exp Neurol. 2000 Oct;165(2):327-41
10993692
Neurology. 1999 Apr 22;52(7):1427-33
10227630
J Neurosci. 1995 Dec;15(12):7929-39
8613731
J Neurophysiol. 2007 Jul;98(1):478-87
17493926
Muscle Nerve. 2004 Dec;30(6):774-83
15478121
J Neurophysiol. 1987 Jul;58(1):105-24
3039077
Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9614-9
9689129
Science. 1995 Mar 17;267(5204):1658-62
7886457
Amyotroph Lateral Scler Other Motor Neuron Disord. 2000 Jun;1(3):201-6
11464953
Nat Rev Neurosci. 2001 Jan;2(1):24-32
11253356
Neuron. 2005 Apr 7;46(1):13-21
15820690
Exp Neurol. 2003 Jun;181(2):115-29
12781986
Exp Neurol. 1997 Dec;148(2):475-94
9417827
Nat Neurosci. 2000 Apr;3(4):323-9
10725920
Brain Res. 2004 Jul 9;1013(2):174-81
15193526
J Neurosci. 2001 Nov 1;21(21):8680-9
11606656
J Appl Physiol (1985). 1989 Jun;66(6):2539-45
2745316
Neurosci Lett. 2002 Apr 19;323(1):25-8
11911982
J Appl Physiol (1985). 1997 Apr;82(4):1145-53
9104851
J Neurosci. 1999 Jul 1;19(13):5173-84
10377329
Nat Neurosci. 2004 Jan;7(1):48-55
14699417
Pain. 2002 Nov;100(1-2):171-81
12435470
J Neurosci. 1998 Oct 15;18(20):8436-43
9763486
Learn Mem. 2003 Mar-Apr;10(2):86-98
12663747
Neuroreport. 1994 Dec 30;6(1):21-5
7703418
Neuroreport. 1999 Mar 17;10(4):889-93
10208566
J Appl Physiol (1985). 2001 Dec;91(6):2665-73
11717232
Muscle Nerve. 1999 Mar;22(3):307-19
10086891
J Appl Physiol (1985). 2000 Aug;89(2):563-72
10926639
Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11282-6
1333605
J Neurophysiol. 1987 Jan;57(1):245-59
3559674
J Neurophysiol. 1976 Jul;39(4):844-51
966042
J Neurotrauma. 2006 May;23(5):617-34
16689666
J Comp Neurol. 2002 Oct 21;452(3):255-63
12353221
J Appl Physiol (1985). 2001 Dec;91(6):2451-8
11717204
J Neurosci Methods. 2009 Sep 15;182(2):244-9
19559048
Neurobiol Dis. 2000 Dec;7(6 Pt B):574-85
11114257
Amyotroph Lateral Scler Other Motor Neuron Disord. 2005 Jun;6(2):100-3
16036433
Philos Trans R Soc Lond B Biol Sci. 2006 Sep 29;361(1473):1545-64
16939974
Annu Rev Neurosci. 2001;24:677-736
11520916
Exp Neurol. 2005 Feb;191(2):344-60
15649491
J Appl Physiol (1985). 2003 Mar;94(3):1230-41
12571144
J Neurophysiol. 1990 Aug;64(2):423-36
1976765
J Comp Neurol. 1990 Dec 22;302(4):707-14
1707065
Exp Neurol. 2001 Jun;169(2):407-15
11358454
J Neurophysiol. 1979 Jan;42(1 Pt 1):76-90
430115
Neuropharmacology. 2002 Jun;42(7):903-12
12069900
J Neurotrauma. 2005 Feb;22(2):203-13
15716627
J Physiol. 1895 Apr 6;17(6):455-85
16992199