Furey Matthew J, Midha Rajiv, Xu Qing-Gui, Belkas Jason, Gordon Tessa
Center for Neuroscience, University of Alberta, Edmonton, Canada.
Neurosurgery. 2007 Apr;60(4):723-32; discussion 732-3. doi: 10.1227/01.NEU.0000255412.63184.CC.
To investigate whether or not it is the frustrated growth state (no axon growth) that reduces regenerative capacity or the inability of axotomized motoneurons to remake muscle connections (axon growth-no muscle contact) that accounts for poor regenerative capacity of chronically axotomized motoneurons.
We chronically axotomized rat femoral motoneurons for 2 months by cutting the nerve and either capping the proximal nerve to prevent axon regeneration (Group 1, no axon growth for 2 mo) or encouraging axon regeneration but not target reinnervation by suture to the distal stump of cut saphenous nerve (Group 2, axon growth with no muscle contact). In the control fresh axotomy group (axon growth with muscle contact), femoral nerve stumps were resutured immediately. Two months later, the femoral nerve was recut and sutured immediately to encourage regeneration in a freshly cut saphenous nerve stump for 6 weeks. Regenerating axons in the saphenous nerve were back-labeled with fluorogold for enumeration of the femoral motoneurons that regenerated their axons into the distal nerve stump.
We found that significantly fewer chronically axotomized motoneurons regenerated their axons than freshly axotomized motoneurons that regenerated their axons to reform nerve-muscle connections in the same length of time. The number of motoneurons that regenerated their axons was reduced in both the conditions of no axon growth and axon growth with no muscle contact; thus chronic axotomy for a 2-month period reduced regenerative success irrespective of whether the motoneurons were prevented from regenerating or encouraged to regenerate their axons in that same period of time.
Axonal regeneration does not protect motoneurons from the negative effects of prolonged axotomy on regenerative capacity. It is the period of chronic axotomy, in which motoneurons remain without target nerve-muscle connection, and not simply a state of frustrated growth that accounts for the reduced regenerative capacity of those neurons.
研究是受挫的生长状态（无轴突生长）降低了再生能力，还是轴突切断后的运动神经元无法重新建立肌肉连接（轴突生长但无肌肉接触）导致慢性轴突切断的运动神经元再生能力差。
我们通过切断神经对大鼠股运动神经元进行慢性轴突切断2个月，要么封闭近端神经以防止轴突再生（第1组，2个月无轴突生长），要么通过缝合到切断的隐神经远端残端来促进轴突再生但不进行靶再支配（第2组，轴突生长但无肌肉接触）。在对照新鲜轴突切断组（轴突生长且有肌肉接触）中，股神经残端立即重新缝合。两个月后，再次切断股神经并立即缝合，以促进在新鲜切断的隐神经残端中再生6周。用荧光金对隐神经中的再生轴突进行逆行标记，以计数其轴突再生到远端神经残端的股运动神经元。
我们发现，与在相同时间内轴突再生以重新形成神经 - 肌肉连接的新鲜轴突切断的运动神经元相比，慢性轴突切断的运动神经元再生轴突的数量明显减少。在无轴突生长和轴突生长但无肌肉接触的两种情况下，再生轴突的运动神经元数量均减少；因此，2个月的慢性轴突切断降低了再生成功率，无论运动神经元在此期间是被阻止再生还是被鼓励再生轴突。
轴突再生并不能保护运动神经元免受长期轴突切断对再生能力的负面影响。是慢性轴突切断期，在此期间运动神经元一直没有靶神经 - 肌肉连接，而不仅仅是受挫的生长状态导致了这些神经元再生能力的降低。
