Effects of repetitive conditioning crush lesions on regeneration of the rat sciatic nerve

̈berg, Jacob Sjo; Kanje, Martin

doi:10.1016/0006-8993(90)90676-3

Cited by 25 publications

(11 citation statements)

References 19 publications

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“…The increased axonal outgrowth from the exercise-conditioned neurons closely resembles the conditioning effect of peripheral axotomy, where distal nerve injury primes neurons for more rapid axonal regeneration after a second injury placed proximal to the ''conditioning'' injury (27)(28)(29). In an analogous fashion, our results show enhanced nerve regeneration in animals that had exercised for 7 days compared with sedentary animals.…”

Section: Discussionsupporting

confidence: 70%

Voluntary exercise increases axonal regeneration from sensory neurons

Molteni

Zheng

Ying

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

167

128

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Recent advances in understanding the role of neurotrophins on activity-dependent plasticity have provided insight into how behavior can affect specific aspects of neuronal biology. We present evidence that voluntary exercise can prime adult dorsal root ganglion neurons for increased axonal regeneration through a neurotrophin-dependent mechanism. Dorsal root ganglion neurons showed an increase in neurite outgrowth when cultured from animals that had undergone 3 or 7 days of exercise compared with sedentary animals. Neurite length over 18 -22 h in culture correlated directly with the distance that animals ran. The exerciseconditioned animals also showed enhanced regrowth of axons after an in vivo nerve crush injury. Sensory ganglia from the 3-and 7-day-exercised animals contained higher brain-derived neurotrophic factor, neurotrophin 3, synapsin I, and GAP43 mRNA levels than those from sedentary animals. Consistent with the rise in brain-derived neurotrophic factor and neurotrophin 3 during exercise, the increased growth potential of the exercise-conditioned animals required activation of the neurotrophin signaling in vivo during the exercise period but did not require new mRNA synthesis in culture.neurotrophin ͉ gene expression ͉ plasticity ͉ neural activity ͉ experience A lterations in neuronal activity can lead to lasting changes in the ability of the nervous system to transduce information (1). Such synaptic plasticity is well documented in the developing nervous system where the levels of neuronal activity can influence the eventual organization of cortical circuits (2). More recent studies (3) indicate that activity-dependent plasticity is retained into adulthood. The morphological basis of lasting forms of activity-dependent synaptic plasticity is manifest as an overall change in the number and͞or area of synaptic contacts (1-3). In the developed organism, both of these processes require remodeling of synaptic structures, either through retraction of existing neuronal processes or by growth of new neuronal processes.Formation of synaptic contacts and growth is a dynamic process that is largely affected through interactions with the environment, such that experience can imprint the nervous system by regulating these events (3). Neurotrophins, originally described for their role on growth and differentiation of neurons, are becoming recognized as regulators of synaptic plasticity (4, 5). The levels of the neurotrophins and͞or their receptors can be altered by neuronal activity, thus providing a potential means to perpetuate changes in synaptic transmission (6, 7). Brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) are important for the regulation of sensorimotor function taking place at the muscle-dorsal root ganglion (DRG)-spinal cord interface (8-10). We previously showed that the expression of BDNF and NT-3 is increased in the spinal cord and skeletal muscle after voluntary exercise and this alters expression of synapsin I mRNA in motor neurons (11-13). Here, we have asked how voluntary exer...

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Section: Discussionsupporting

confidence: 70%

Voluntary exercise increases axonal regeneration from sensory neurons

Molteni

Zheng

Ying

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

167

128

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“…The immunopositive area for evaluation of p-ERK1/2 was present more predominantly at the site of the nerve lesion after immediate nerve repair, where 3 [H]-thymidine incorporation is maximal after a nerve injury [22,23]. The increased presence of p-ERK1/2 at site of lesion after immediate repair could be related to contact between Schwann cells and regenerating axons [24] and to a cellular response similar as suggested for STAT-3 in the distal nerve segment far from site of lesion [15].…”

Section: Discussionmentioning

confidence: 99%

“…first injury, can improve axonal outgrowth after a second lesion [25]. However, conditioning by transection [26] has a lower effect on axonal outgrowth than that of a conditioning crush lesion [23]. …”

Section: Discussionmentioning

confidence: 99%

Axonal outgrowth is associated with increased ERK 1/2 activation but decreased caspase 3 linked cell death in Schwann cells after immediate nerve repair in rats

2011

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BackgroundExtracellular-signal regulated kinase (ERK1/2) is activated by nerve damage and its activation precedes survival and proliferation of Schwann cells. In contrast, activation of caspase 3, a cysteine protease, is considered as a marker for apoptosis in Schwann cells. In the present study, axonal outgrowth, activation of ERK1/2 by phosphorylation (p-ERK 1/2 ) and immunoreactivity of cleaved caspase 3 were examined after immediate, delayed, or no repair of transected rat sciatic nerves.ResultsAxonal outgrowth, detected by neurofilament staining, was longer after immediate repair than after either the delayed or no repair conditions. Immediate repair also showed a higher expression of p-ERK 1/2 and a lower number of cleaved caspase 3 stained Schwann cells than after delayed nerve repair. If the transected nerve was not repaired a lower level of p-ERK 1/2 was found than in either the immediate or delayed repair conditions. Axonal outgrowth correlated to p-ERK 1/2, but not clearly with cleaved caspase 3. Contact with regenerating axons affected Schwann cells with respect to p-ERK 1/2 and cleaved caspase 3 after immediate nerve repair only.ConclusionThe decreased regenerative capacity that has historically been observed after delayed nerve repair may be related to impaired activation of Schwann cells and increased Schwann cell death. Outgrowing axons influence ERK 1/2 activation and apoptosis of Schwann cells.

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“…Downstream programs of neurite outgrowth are initiated, including reorganization of microtubules and microfilaments, upregulated expression of GAP-43 (a growth cone path-finding protein associated with nerve growth and plasticity) (Gold et al, 1998;Madsen et al, 1998), and potential crosstalk with signal transduction pathways for neurotrophic factors like NGF . As has been noted previously (Yan et al, 2011), the first injury in the saphenous nerve crush model induces a pre-conditioned nerve injury state that enhances the regenerative response to the second crush injury (McQuarrie, 1978;Forman et al, 1980;Sjoberg and Kanje, 1990;Lankford et al, 1998). Like FK-506, GA provides an additional benefit to nerve regeneration above that of pre-conditioning.…”

Section: Discussionmentioning

confidence: 77%