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Axotomized motoneurons can be rescued from cell death by peripheral nerve grafts: The effect of donor age

Low, HL; Nogradi, A; Vrbova, G; Greensmith, L; (2003) Axotomized motoneurons can be rescued from cell death by peripheral nerve grafts: The effect of donor age. J NEUROPATH EXP NEUR , 62 (1) 75 - 87.

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Abstract

Injury to neonatal nerves, unlike adult nerves, results in poor regeneration and extensive motoneuron death. We examined whether exposure to a more mature nerve environment could rescue axotomized motoneurons following neonatal injury. The sciatic nerve in 1 hindlimb of 3-day-old (P3) rats was transected and the cut end sutured to a nerve graft taken from donor rats, which ranged between P3 and P21. The extent of motoneuron survival and axon regeneration was established 7 days later. Since integrins play an important role in regeneration, we also examined the effect of manipulating integrin binding in nerve grafts. Following axotomy at P3 and implantation of nerve grafts from 3-day-old rats, approximately 38% of motoneurons survived. In contrast, grafts from rats aged 5 days and older resulted in an improvement in regeneration, and over 70% of motoneurons survived. This survival-promoting effect of P5 grafts was prevented by blocking beta(1)-integrins. In contrast, increasing beta(1)-integrin levels in grafts from P3 rats dramatically increased motoneuron survival. Thus, following neonatal nerve injury, exposure to a more mature nerve environment significantly increases motoneuron survival, an effect that is dependent upon beta(1)-integrin signaling. Therefore, pharmacological upregulation of beta(1)-integrins may significantly improve the outcome of neonatal nerve injuries.

Type:Article
Title:Axotomized motoneurons can be rescued from cell death by peripheral nerve grafts: The effect of donor age
Keywords:axons, axotomy, beta(1)-integrins, development, motoneuron survival, neurofilaments, regeneration, RAT SPINAL MOTONEURONS, TRANSMITTER RELEASE, SCHWANN-CELLS, NEUROMUSCULAR-JUNCTIONS, POSTNATAL-DEVELOPMENT, NEUROTROPHIC FACTORS, AXONAL REGENERATION, MOTOR-NEURONS, NEWBORN RATS, SURVIVAL
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > Motor Neuroscience and Movement Disorders
UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of)

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