Regeneration of motor axons in the rat sciatic nerve studied by labeling with axonally transported radioactive proteins

Forman, David S.; Berenberg, Richard A.

doi:10.1016/0006-8993(78)90504-8

Cited by 151 publications

(68 citation statements)

References 25 publications

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“…Previous studies have demonstrated that GAP-43, also known as B-50 (Nielander et al, 1987), GAP-48, Fl (Rosenthal et al, 1987), pp46 (Meiri et al, 1986), and P57 (Cimler et al, 1987), is a fast axonally transported phosphoprotein that is important in axon growth (Benowitz and Routtenberg, 1987;Skene, 1989;Stewart et al, 1993) and its phosphorylation by protein kinase C has been implicated in long term potentiation, signal transduction, and neurotransmitter release (Linden et al, 1988;Vanhooff et al, 1988;Nairn and Shenolikar, 1992;Swope et al, 1992). GAP-43 protein content and mRNA expression are upregulated in both the PNS (Forman and Berenberg, 1978) and CNS (Skene and Willard, 1981;Benowitz and Schmidt, 1987) following axotomy and levels of GAP-43 protein increase dramatically in the dentate gyms following an EC lesion, coincident with the expansion of the C/A fiber plexus into the middle molecular layer of the dentate gyrus (Benowitz et al, 1990). In addition, previous studies have found that there is a twofold increase in the transport of newly synthesized GAP-43 to the AGED NF-88 mRNA contralateral hippocampus between 6 and 15 d following an EC lesion, a time when sprouting from C/A axons occurs (Lin et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Lesion-induced sprouting of commissural/associational axons and induction of GAP-43 mRNA in hilar and CA3 pyramidal neurons in the hippocampus are diminished in aged rats

et al. 1995

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Removal of synaptic connections following a partial deafferentation lesion results in a sprouting of remaining afferents that terminate near the denervated area. However, while the ability to form new synapses in response to injury has been reported in both young and aged rats, previous studies have suggested that the injury-induced response in the hippocampus of aged rats may be delayed and/or not as extensive as compared to young adults. Given that growth associated proteins are central for the regulation of neurite outgrowth during both development and regeneration, we were interested in determining if the magnitude and time course of the sprouting response of hippocampal neurons to deafferentation might correlate with induction of growth associated proteins and whether these parameters could be modulated with age. For our studies we used the Holmes fiber stain to determine the expansion of the C/A fiber plexus following denervation and compared the time course of the sprouting response with that observed by in situ hybridization for the neurite outgrowth proteins, growth associated protein-43 (GAP-43), superior cervical ganglion-10 (SCG-10), and neurofilament-68 (NF-68) at various time points after the lesion for each age group. We found that the commissural/associational (C/A) fiber plexus expanded by 45% in young adult rats at 30 and 45 d postlesion and was accompanied by a significant increase in expression of GAP-43 mRNA in both ipsilateral and contralateral hilar and CA3 pyramidal neurons, the cell bodies of origin for the C/A pathway. In contrast, a dampened sprouting response was observed in aged rats at all time points postlesion and coincided with a lack of induction of any of the growth-associated proteins. These results suggest that GAP-43 is involved in outgrowth of C/A axons in the hippocampus in response to a partial deafferentation lesion. However, factors that stimulate neurite outgrowth and upregulate GAP-43 mRNA in response to a partial deafferentation lesion diminish with age.

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Section: Discussionmentioning

confidence: 99%

Lesion-induced sprouting of commissural/associational axons and induction of GAP-43 mRNA in hilar and CA3 pyramidal neurons in the hippocampus are diminished in aged rats

et al. 1995

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“…In the regeneration speed experiments, fast axonal transport was used to determine the locations of regenerating motor fibers either 4 or 8 d after regeneration was initiated by crushing the sciatic nerve, with or without electrical stimulation (Forman and Berenberg, 1978). Crush was chosen to initiate regeneration to eliminate the confounding effects of regeneration stagger that accompany nerve transection and suture.…”

Section: Methodsmentioning

confidence: 99%

“…However, use of radiotracers to pinpoint the location of growth cones throughout the nerve should be more informative. In fact, both studies of transected and sutured nerve (Forman and Berenberg, 1978;Danielsen et al, 1986) identified substantial numbers of axons that failed to Fig. 1).…”

Section: Staggered Regenerationmentioning

confidence: 98%

“…Attempts to quantify axon behavior after peripheral nerve transection and repair have focused on the number of axons regenerating (Jenq and Coggeshall, 1984;Scherer and Easter, 1984;Mackinnon et al, 1991), their speed (Forman and Berenberg, 1978;Forman et al, 1979;Danielsen et al, 1986;Jacquin et al, 1992), and their initial delay at the suture line (Forman et al, 1979;Danielsen et al, 1986;Holmquist et al, 1993). The asynchrony of axon regeneration, which we have termed "staggered regeneration," has received little attention.…”

Section: Staggered Regenerationmentioning

confidence: 99%

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Electrical Stimulation Promotes Motoneuron Regeneration without Increasing Its Speed or Conditioning the Neuron

Hoffman²,

et al. 2002

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Motoneurons reinnervate the distal stump at variable rates after peripheral nerve transection and suture. In the rat femoral nerve model, reinnervation is already substantial 3 weeks after repair, but is not completed for an additional 7 weeks. However, this "staggered regeneration" can be temporally compressed by application of 20 Hz electrical stimulation to the nerve for 1 hr. The present experiments explore two possible mechanisms for this stimulation effect: (1) synchronization of distal stump reinnervation and (2) enhancement of regeneration speed. The first possibility was investigated by labeling all motoneurons that have crossed the repair at intervals from 4 d to 4 weeks after rat femoral nerve transection and suture. Although many axons did not cross until 3-4 weeks after routine repair, stimulation significantly increased the number crossing at 4 and 7 d, with only a few crossing after 2 weeks. Regeneration speed was studied by radioisotope labeling of transported proteins and by anterograde labeling of regenerating axons, and was not altered by stimulation. Attempts to condition the neuron by stimulating the femoral nerve 1 week before injury were also without effect. Electrical stimulation thus promotes the onset of motor axon regeneration without increasing its speed. This finding suggests a combined approach to improving the outcome of nerve repair, beginning with stimulation to recruit all motoneurons across the repair, followed by other treatments to speed and prolong axonal elongation.

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“…One must keep in mind that nerve regeneration and reinnervation is a slow process, in the order of about 1-4 mm/day [9][10][11]. Thus, serial EMG testing may be helpful to monitor recovery.…”

Section: Discussionmentioning

confidence: 99%

Brachial Plexopathy/Nerve Root Avulsion in a Football Player: The Role of Electrodiagnostics

et al. 2008

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Electromyography (EMG) studies are a useful tool in anatomical localization of peripheral nerve and brachial plexus injuries. They are especially helpful in distinguishing between brachial plexopathy and nerve root injuries where surgical intervention may be indicated. EMG can also assist in providing prognostic information after nerve injury as well as after nerve repair. In this case report, a football player presented with weakness in his right upper limb after a traction/traumatic injury to the right brachial plexus. EMG studies revealed evidence of both pre-and postganglionic injury to multiple cervical roots. The injury was substantial enough to cause nerve root avulsions involving the C6 and C7 levels. Surgical referral led to nerve grafts targeted at regaining function in shoulder abduction and elbow flexion. After surgery, the patient's progress was monitored utilizing EMG to assist in identifying true axonal regeneration.

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Regeneration of motor axons in the rat sciatic nerve studied by labeling with axonally transported radioactive proteins

Cited by 151 publications

References 25 publications

Lesion-induced sprouting of commissural/associational axons and induction of GAP-43 mRNA in hilar and CA3 pyramidal neurons in the hippocampus are diminished in aged rats

Lesion-induced sprouting of commissural/associational axons and induction of GAP-43 mRNA in hilar and CA3 pyramidal neurons in the hippocampus are diminished in aged rats

Electrical Stimulation Promotes Motoneuron Regeneration without Increasing Its Speed or Conditioning the Neuron

Brachial Plexopathy/Nerve Root Avulsion in a Football Player: The Role of Electrodiagnostics

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