The use of ciliary neurotrophic factor to promote recovery after peripheral nerve injury by delivering it at the site of the cell body

被引：16

作者：

Kelleher M.O. ^{[1
]}

Myles L.M. ^{[2
]}

Al-Abri R.K. ^{[2
]}

Glasby M.A. ^{[2
]}

机构：

[1] Department of Neurosurgery, Beaumont Hospital, Dublin

[2] Department of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Edinburgh

来源：

Acta Neurochirurgica | 2006年 / 148卷 / 1期

关键词：

CNTF; Intrathecal; Nerve repair; Neurotrophic factors;

D O I：

10.1007/s00701-005-0631-2

中图分类号：

学科分类号：

摘要：

Despite a body of evidence showing that various neurotrophic factors support the survival of nerve cells and stimulate axonal outgrowth, doubt remains about their optimal site of application as well as the more compelling question of what clinical benefit, if any, they would confer. Ciliary neurotrophic factor (CNTF) supports the survival of motorneurons in vitro and in vivo. Direct delivery of CNTF to the cell bodies may help reduce the side effects and overcome the problem of rapid systemic clearance. The aim of this study was to establish whether nerve regeneration may be improved upon by the controlled addition of a specific humoral neurotrophic substance (CNTF) at the level of the cell body. Three groups of five adult sheep were used. The first group acted as normal controls. In the second and third groups, the median nerve was divided and repaired using an epineurial suture technique. In the second group, CNTF was supplied into the CSF at the level of C6 by an implanted osmotic pump. In the third group physiological saline was placed in the osmotic pump. The animals underwent comprehensive electrophysiological and isometric tension experiments at six months. All of the animals had reduced electrophysiological, morphometric and isometric tension indices after surgery compared to normal. The CNTF group had better results than the saline group in the following; (1) area and amplitude of the muscle action potential (2) the percentage of tetanus and muscle mass preserved after repair. These differences were only statistically significant for amplitude of the muscle action potential. No statistical difference was found in the morphological indices (fibre diameter, axon diameter, myelin thickness and internodal length) between the CNTF and saline groups. CNTF does not confer a functional benefit when applied at the level of the cell body. © Springer-Verlag 2005.

引用

页码：55 / 60

页数：5

共 27 条

[1]

Manthorpe M., Skaper S., Adler R., Landa K., Varon S., Cholinergic neuronotrophic factors: Fractionation properties of an extract from selected chick embryonic eye tissues., J Neurochem, 34, pp. 69-75, (1980)

[2]

Sendtner M., Carroll P., Holtmann B., Hughes R.A., Thoenen H., Ciliary neurotrophic factor., J Neurobiol, 25, pp. 1436-1453, (1994)

[3]

Oppenheim R.W., Prevette D., Yin Q.W., Collins F., MacDonald J., Control of embryonic motoneuron survival in vivo by ciliary neurotrophic factor., Science, 251, pp. 1616-1618, (1991)

[4]

Li L., Oppenheim R.W., Lei M., Houenou L.J., Neurotrophic agents prevent motoneuron death following sciatic nerve section in the neonatal mouse., J Neurobiol, 25, pp. 759-766, (1994)

[5]

Sendtner M., Kreutzberg G.W., Thoenen H., Ciliary neurotrophic factor prevents the degeneration of motor neurons after axotomy., Nature, 345, pp. 440-441, (1997)

[6]

Kwon Y.W., Gurney M.E., Systemic injections of ciliary neurotrophic factor induce sprouting by adult motor neurons., NeuroReport, 5, pp. 789-792, (1994)

[7]

Gurney M.E., Yamamoto H., Kwon Y., Induction of motor neuron sprouting in vivo by ciliary neurotrophic factor and basic fibroblast growth factor., J Neurosci, 12, pp. 3241-3247, (1992)

[8]

Lewin S.L., Utley D.S., Cheng E.T., Verity A.N., Terris D.J., Simultaneous treatment with BDNF and CNTF after peripheral nerve transection and repair enhances rate of functional recovery compared with BDNF treatment alone., Laryngoscope, 107, pp. 992-999, (1997)

[9]

Sahenk Z., Seharaseyon J., Mendell J.R., CNTF potentiates peripheral nerve regeneration., Brain Res, 655, pp. 246-250, (1994)

[10]

Dittrich F., Thoenen H., Sendtner M., Ciliary neurotrophic factor: Pharmacokinetics and acute-phase response in rat., Ann Neurol, 35, pp. 151-163, (1994)

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