Deep Brain Stimulation of the Midbrain Locomotor Region Improves Paretic Hindlimb Function After Spinal Cord Injury in Rats

被引:88
作者
Bachmann, Lukas C. [1 ,2 ]
Matis, Alina [1 ,2 ]
Lindau, Nicolas T. [1 ,2 ]
Felder, Petra [1 ,2 ]
Gullo, Miriam [1 ,2 ]
Schwab, Martin E. [1 ,2 ]
机构
[1] Univ Zurich, Brain Res Inst, CH-8057 Zurich, Switzerland
[2] ETH, Dept Hlth Sci & Technol, CH-8057 Zurich, Switzerland
基金
瑞士国家科学基金会;
关键词
PEDUNCULOPONTINE NUCLEUS; PARKINSONS-DISEASE; RETICULAR-FORMATION; ANTI-NOGO; INTRASPINAL MICROSTIMULATION; RETICULOSPINAL NEURONS; TREADMILL LOCOMOTION; FICTIVE LOCOMOTION; BASAL GANGLIA; MOTOR CORTEX;
D O I
10.1126/scitranslmed.3005972
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
In severe spinal cord injuries, the tracts conveying motor commands to the spinal cord are disrupted, resulting in paralysis, but many patients still have small numbers of spared fibers. We have found that excitatory deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR), an important control center for locomotion in the brain, markedly improved hindlimb function in rats with chronic, severe, but incomplete spinal cord injury. The medial medullary reticular formation was essential for this effect. Functional deficits of rats with 20 to 30% spared reticulospinal fibers were comparable to patients able to walk but with strong deficits in strength and speed [for example, individuals with American Spinal Injury Association Impairment Scale (AIS)-D scores]. MLR DBS enabled close to normal locomotion in these rats. In more extensively injured animals, with less than 10% spared reticulospinal fibers, hindlimbs were almost fully paralyzed, comparable to wheelchair-bound patients (for example, AIS-A, B, and C). With MLR DBS, hindlimb function reappeared under gravity-released conditions during swimming. We propose that therapeutic MLR DBS using the brain's own motor command circuits may offer a potential new approach to treat persistent gait disturbances in patients suffering from chronic incomplete spinal cord injury.
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页数:14
相关论文
共 76 条
[1]   The pedunculopontine nucleus area: critical evaluation of interspecies differences relevant for its use as a target for deep brain stimulation [J].
Alam, Mesbah ;
Schwabe, Kerstin ;
Krauss, Joachim K. .
BRAIN, 2011, 134 :11-23
[2]   Imaging the spread of reversible brain inactivations using fluorescent muscimol [J].
Allen, Timothy A. ;
Narayanan, Nandakumar S. ;
Kholodar-Smith, Dianna B. ;
Zhao, Yanjun ;
Laubach, Mark ;
Brown, Thomas H. .
JOURNAL OF NEUROSCIENCE METHODS, 2008, 171 (01) :30-38
[3]  
ARMSTRONG DM, 1988, J PHYSIOL-LONDON, V405, P1, DOI 10.1113/jphysiol.1988.sp017319
[4]   NORADRENERGIC AGONISTS AND LOCOMOTOR TRAINING AFFECT LOCOMOTOR RECOVERY AFTER CORD TRANSECTION IN ADULT CATS [J].
BARBEAU, H ;
CHAU, C ;
ROSSIGNOL, S .
BRAIN RESEARCH BULLETIN, 1993, 30 (3-4) :387-393
[5]   RECOVERY OF LOCOMOTION AFTER CHRONIC SPINALIZATION IN THE ADULT CAT [J].
BARBEAU, H ;
ROSSIGNOL, S .
BRAIN RESEARCH, 1987, 412 (01) :84-95
[6]   Characteristics and mechanisms of locomotion induced by intraspinal microstimulation and dorsal root stimulation in spinal cats [J].
Barthelemy, D. ;
Leblond, H. ;
Rossignol, S. .
JOURNAL OF NEUROPHYSIOLOGY, 2007, 97 (03) :1986-2000
[7]  
BELOOZEROVA IN, 1993, J PHYSIOL-LONDON, V461, P1
[8]   Differential effects of brain-derived neurotrophic factor and neurotrophin-3 on hindlimb function in paraplegic rats [J].
Boyce, Vanessa S. ;
Park, Jihye ;
Gage, Fred H. ;
Mendell, Lorne M. .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2012, 35 (02) :221-232
[9]  
Cabelguen JM, 2003, J NEUROSCI, V23, P2434
[10]   Transformation of nonfunctional spinal circuits into functional states after the loss of brain input [J].
Courtine, Gregoire ;
Gerasimenko, Yury ;
van den Brand, Rubia ;
Yew, Aileen ;
Musienko, Pavel ;
Zhong, Hui ;
Song, Bingbing ;
Ao, Yan ;
Ichiyama, Ronaldo M. ;
Lavrov, Igor ;
Roy, Roland R. ;
Sofroniew, Michael V. ;
Edgerton, V. Reggie .
NATURE NEUROSCIENCE, 2009, 12 (10) :1333-U167