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Recovery of motor control after hemisection of the spinal cord in primate: electrophysiological study

English title Recovery of motor control after hemisection of the spinal cord in primate: electrophysiological study
Applicant Belhaj-Saif Abderraouf
Number 120411
Funding scheme Project funding (Div. I-III)
Research institution Département de Médecine Université de Fribourg
Institution of higher education University of Fribourg - FR
Main discipline Neurophysiology and Brain Research
Start/End 01.09.2008 - 31.12.2011
Approved amount 335'392.00
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Keywords (5)

spinal lesion; EMG; Stimulus triggered averaging; Monkey; Behavioral

Lay Summary (English)

Lay summary
In the USA, for example, spinal cord injury affects between 250,000 and 350,000 Americans with 6,000 to 10,000 new cases each year. Most of these injuries include damage to the major pathways descending from the brain to the spinal cord. These tracts carry the signals from the brain that eventually engage the activity of muscles to initiate and control voluntary movements. The corticospinal tract is one of these pathways. It arises from the cerebral cortex of the brain and is particularly important for skilled voluntary movements involving the distal extremities, especially the hand. The ability of the nervous system to partially compensate for injury to the corticospinal pathway is widely accepted both from experimental studies in animals and from clinical reports in humans. However, the mechanisms underlying this motor recovery process are not understood. In the past decade, enormous progress was achieved in our understanding of the post-lesion plasticity of the central nervous system in the adult in general and in the spinal cord in particular. This progress was particularly due to the discovery of an antibody neutralizing neurite growth inhibitors (Anti-Nogo-A) by Prof. Martin Schwab (University of Zürich). In fact, the anti-Nogo-A treatment in non-human primate (macaca fascicularis, mulatta) following unilateral lesion of the cervical spinal cord at the level of C7/C8 produced a significant recovery of the manual hand dexterity. The anatomical results showed significant outgrowth of new projections around the lesion site for the treated monkeys and none or only a limited one in monkeys treated with a control antibody. Such corticospinal sprouting reached up to 10 to 12 mm caudal to the lesion site. Taking together, these findings suggest that these new projections are the anatomical support for the hand dexterity improvement. Moreover, it suggests that these projections reach directly or indirectly the motor nuclei that controls distal forelimb muscles, which explain the observed recovery of the hand dexterity. Nevertheless, at that step, there is no evidence showing the functional role of such re-established projections.The goal of the present proposal is to investigate the function of these new projections, by taking advantage of the strengths of the technique “stimulus triggered averaging” of EMG activity from chronically recorded forelimb muscles in monkeys subjected to spinal cord lesion. We have applied extensively this technique in the past to investigate the proprieties of the corticospinal and rubrospinal projections in healthy animals and red nucleus output reorganization following corticospinal lesion in Prof. Cheney’s laboratory. In this project, we will focus principally on the primary motor cortex (M1). Specifically, we propose to directly investigate the factors contributing to recovery of motor function in non-human primates with injury to the corticospinal tract following anti-Nogo-A antibody treatment. The hypothesis we plan to test is that the sprouting fibers of descending pathway promoted with anti-Nogo-A antibody treatment along with "spared" corticospinal neurons, change their properties so as to compensate for motor function lost as a result of the injury. These changes may take the form of strengthened connections with motoneurons in the spinal cord or enhancement of the signals transmitted to the motoneurons. A greater understanding of the neural mechanisms involved might suggest methods of manipulating and enhancing the recovery process.For this purpose, four adult monkeys will be trained in various tasks involving mainly hand dexterity. Once the monkeys will reach high performance in all tasks a lesion of one side the spinal cord will be performed under deep anesthesia. This lesion will interrupt axons innervating the motoneurons of the hand muscles which disable the fine finger movements. Two animals will be treated with anti-Nogo-A antibody and the other two with a control antibody. Collaborators:E.M. Rouiller: Dept. Med. Univ. Fribourg, 1700 Fribourg, Switzerland J. Bloch: Dept. Neurosurg., Univ. Lausanne, 1011 Lausanne, Switzerland A. Mir: Inst. Biomed. Res., Novartis, 4002 Basel, Switzerland M.E. Schwab: Dept. Neuromorphol. Univ. Zurich, 8057 Zurich, Switzerland P.D Cheney: Dept. Molecul. & Physiol. Integr. Univ. Kansas Med. Ctr. Kansas City, KS 66160 Kansas, USA.
Direct link to Lay Summary Last update: 21.02.2013

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