Vagus Nerve Stimulation During Rehabilitative Training Improves Forelimb Recovery After Chronic Ischemic Stroke in Rats

被引：107

作者：

Khodaparast, Navid ^{[1
]}

Kilgard, Michael P. ^{[1
]}

Casavant, Reema ^{[2
]}

Ruiz, Andrea ^{[1
]}

Qureshi, Iqra ^{[1
]}

Ganzer, Patrick D. ^{[1
]}

Rennaker, Robert L., II ^{[1
]}

Hays, Seth A. ^{[1
]}

机构：

[1] Univ Texas Dallas, Richardson, TX 75080 USA

[2] Micro Transponder Inc, Dallas, TX 75204 USA

来源：

NEUROREHABILITATION AND NEURAL REPAIR | 2016年 / 30卷 / 07期

关键词：

vagus nerve; vagal stimulation; ischemic stroke; recovery; rehabilitation; FOCAL CEREBRAL-ISCHEMIA; MICROTUBULE-ASSOCIATED PROTEIN-2; FOREBRAIN CHOLINERGIC SYSTEM; SENSORIMOTOR CORTEX; CORTICAL PLASTICITY; LOCUS-COERULEUS; UPPER-LIMB; LESIONS; NOREPINEPHRINE; GROWTH;

D O I：

10.1177/1545968315616494

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background and objective. Stroke is a leading cause of long-term disability. Currently, there are no consistently effective rehabilitative treatments for chronic stroke patients. Our recent studies demonstrate that vagus nerve stimulation (VNS) paired with rehabilitative training improves recovery of function in multiple models of stroke. Here, we evaluated the ability of VNS paired with rehabilitative training to improve recovery of forelimb strength when initiated many weeks after a cortical and subcortical ischemic lesion in subjects with stable, chronic motor deficits. Methods. Rats were trained to perform an automated, quantitative measure of voluntary forelimb strength. Once proficient, rats received injections of endothelin-1 to cause a unilateral cortical and subcortical ischemic lesion. Then, 6 weeks after the lesion, rats underwent rehabilitative training paired with VNS (Paired VNS; n = 10), rehabilitative training with equivalent VNS delivered 2 hours after daily rehabilitative training (Delayed VNS; n = 10), or rehabilitative training without VNS (Rehab, n = 9). Results. VNS paired with rehabilitative training significantly improved recovery of forelimb function compared with control groups. The Paired VNS group displayed an 86% recovery of strength, the Rehab group exhibited 47% recovery, and the Delayed VNS group exhibited 42% recovery. Improvement in forelimb function was sustained in the Paired VNS group after the cessation of stimulation, potentially indicating lasting benefits. No differences in intensity of rehabilitative training, lesion size, or MAP-2 expression were observed between groups. Conclusion. VNS paired with rehabilitative training confers significantly greater recovery of forelimb function after chronic ischemic stroke in rats.

引用

页码：676 / 684

页数：9

共 47 条

[11] Reversing pathological neural activity using targeted plasticity [J].

Engineer, Navzer D. ;

Riley, Jonathan R. ;

Seale, Jonathan D. ;

Vrana, Will A. ;

Shetake, Jai A. ;

Sudanagunta, Sindhu P. ;

Borland, Michael S. ;

Kilgard, Michael P. .

NATURE, 2011, 470 (7332) :101-U114

[12] Quantitative studies of the vagus nerve in the cat - I. The ratio of sensory to motor fibers [J].

Foley, JO ;

DuBois, F .

JOURNAL OF COMPARATIVE NEUROLOGY, 1937, 67 (01) :49-67

[13] Vagus nerve stimulation increases norepinephrine concentration and the gene expression of BDNF and bFGF in the rat brain [J].

Follesa, Paolo ;

Biggio, Francesca ;

Gorini, Giorgio ;

Caria, Stefania ;

Talani, Giuseppe ;

Dazzi, Laura ;

Puligheddu, Monica ;

Marrosu, Francesco ;

Biggio, Giovanni .

BRAIN RESEARCH, 2007, 1179 :28-34

[14] Vagal Nerve Stimulation Rapidly Activates Brain-Derived Neurotrophic Factor Receptor TrkB in Rat Brain [J].

Furmaga, Havan ;

Carreno, Flavia Regina ;

Frazer, Alan .

PLOS ONE, 2012, 7 (05)

[15] Heart Disease and Stroke Statistics-2014 Update A Report From the American Heart Association [J].

Go, Alan S. ;

Mozaffarian, Dariush ;

Roger, Veronique L. ;

Benjamin, Emelia J. ;

Berry, Jarett D. ;

Blaha, Michael J. ;

Dai, Shifan ;

Ford, Earl S. ;

Fox, Caroline S. ;

Franco, Sheila ;

Fullerton, Heather J. ;

Gillespie, Cathleen ;

Hailpern, Susan M. ;

Heit, John A. ;

Howard, Virginia J. ;

Huffman, Mark D. ;

Judd, Suzanne E. ;

Kissela, Brett M. ;

Kittner, Steven J. ;

Lackland, Daniel T. ;

Lichtman, Judith H. ;

Lisabeth, Lynda D. ;

Mackey, Rachel H. ;

Magid, David J. ;

Marcus, Gregory M. ;

Marelli, Ariane ;

Matchar, David B. ;

McGuire, Darren K. ;

Mohler, Emile R., III ;

Moy, Claudia S. ;

Mussolino, Michael E. ;

Neumar, Robert W. ;

Nichol, Graham ;

Pandey, Dilip K. ;

Paynter, Nina P. ;

Reeves, Matthew J. ;

Sorlie, Paul D. ;

Stein, Joel ;

Towfighi, Amytis ;

Turan, Tanya N. ;

Virani, Salim S. ;

Wong, Nathan D. ;

Woo, Daniel ;

Turner, Melanie B. .

CIRCULATION, 2014, 129 (03) :E28-E292

[16]

GOLDSTEIN LB, 1991, RESTOR NEUROL NEUROS, V3, P41, DOI 10.3233/RNN-1991-3105

[17] Recordings from the rat locus coeruleus during acute vagal nerve stimulation in the anaesthetised rat [J].

Groves, DA ;

Bowman, EM ;

Brown, VJ .

NEUROSCIENCE LETTERS, 2005, 379 (03) :174-179

[18] Neuromodulatory transmitter systems in the cortex and their role in cortical plasticity [J].

Gu, Q .

NEUROSCIENCE, 2002, 111 (04) :815-835

[19]

HAYES SH, 1986, ARCH PHYS MED REHAB, V67, P319

[20] Vagus Nerve Stimulation During Rehabilitative Training Improves Functional Recovery After Intracerebral Hemorrhage [J].

Hays, Seth A. ;

Khodaparast, Navid ;

Hulsey, Daniel R. ;

Ruiz, Andrea ;

Sloan, Andrew M. ;

Rennaker, Robert L., II ;

Kilgard, Michael P. .

STROKE, 2014, 45 (10) :3097-+

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