Axonal regeneration in the rat sciatic nerve: Effect of a conditioning lesion and of dbcAMP

McQuarrie, Irvine G.; Grafstein, Bernice; Gershon, Michael D.

doi:10.1016/0006-8993(77)90193-7

Cited by 285 publications

(145 citation statements)

References 15 publications

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“…Preconditioning dramatically ramps up regenerative neurite outgrowth, a mechanism that involves, among others, heightened intracellular cAMP and increased expression of many regenerationassociated genes, including ␤III tubulin, GAP43/B50, and others (McQuarrie and Grafstein, 1973;McQuarrie et al, 1977;Forman et al, 1980;Oblinger and Lasek, 1984;Schreyer and Skene, 1991). Our prediction was that preconditioning would suppress PTEN activity, so that little added benefit would accrue from its inhibition.…”

Section: Inhibition Of Pten At the Protein Level In Vitro Increases Nmentioning

confidence: 91%

PTEN Inhibition to Facilitate Intrinsic Regenerative Outgrowth of Adult Peripheral Axons

Christie¹,

Webber²,

Martinez³

et al. 2010

Journal of Neuroscience

294

281

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In vivo regeneration of peripheral neurons is constrained and rarely complete, and unfortunately patients with major nerve trunk transections experience only limited recovery. Intracellular inhibition of neuronal growth signals may be among these constraints. In this work, we investigated the role of PTEN (phosphatase and tensin homolog deleted on chromosome 10) during regeneration of peripheral neurons in adult Sprague Dawley rats. PTEN inhibits phosphoinositide 3-kinase (PI3-K)/Akt signaling, a common and central outgrowth and survival pathway downstream of neuronal growth factors. While PI3-K and Akt outgrowth signals were expressed and activated within adult peripheral neurons during regeneration, PTEN was similarly expressed and poised to inhibit their support. PTEN was expressed in neuron perikaryal cytoplasm, nuclei, regenerating axons, and Schwann cells. Adult sensory neurons in vitro responded to both graded pharmacological inhibition of PTEN and its mRNA knockdown using siRNA. Both approaches were associated with robust rises in the plasticity of neurite outgrowth that were independent of the mTOR (mammalian target of rapamycin) pathway. Importantly, this accelerated outgrowth was in addition to the increased outgrowth generated in neurons that had undergone a preconditioning lesion. Moreover, following severe nerve transection injuries, local pharmacological inhibition of PTEN or siRNA knockdown of PTEN at the injury site accelerated axon outgrowth in vivo. The findings indicated a remarkable impact on peripheral neuron plasticity through PTEN inhibition, even within a complex regenerative milieu. Overall, these findings identify a novel route to propagate intrinsic regeneration pathways within axons to benefit nerve repair.

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Section: Inhibition Of Pten At the Protein Level In Vitro Increases Nmentioning

confidence: 91%

PTEN Inhibition to Facilitate Intrinsic Regenerative Outgrowth of Adult Peripheral Axons

Christie¹,

Webber²,

Martinez³

et al. 2010

Journal of Neuroscience

294

281

View full text Add to dashboard Cite

show abstract

“…not enhance the rate of axon regeneration [55,97,98]. Findings that rolipram, a type IV inhibitor of the enzyme phosphodiesterase that breaks down cAMP, promoted nerve outgrowth in the CNS inspired our examination of whether local delivery of rolipram might enhance axon regeneration in the PNS [99][100][101].…”

Section: The Effect Of Electrical Stimulation On Nerve Regeneration Imentioning

confidence: 99%

Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans

2016

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Injured peripheral nerves regenerate their lost axons but functional recovery in humans is frequently disappointing. This is so particularly when injuries require regeneration over long distances and/or over long time periods. Fat replacement of chronically denervated muscles, a commonly accepted explanation, does not account for poor functional recovery. Rather, the basis for the poor nerve regeneration is the transient expression of growth-associated genes that accounts for declining regenerative capacity of neurons and the regenerative support of Schwann cells over time. Brief low-frequency electrical stimulation accelerates motor and sensory axon outgrowth across injury sites that, even after delayed surgical repair of injured nerves in animal models and patients, enhances nerve regeneration and target reinnervation. The stimulation elevates neuronal cyclic adenosine monophosphate and, in turn, the expression of neurotrophic factors and other growth-associated genes, including cytoskeletal proteins. Electrical stimulation of denervated muscles immediately after nerve transection and surgical repair also accelerates muscle reinnervation but, at this time, how the daily requirement of long-duration electrical pulses can be delivered to muscles remains a practical issue prior to translation to patients. Finally, the technique of inserting autologous nerve grafts that bridge between a donor nerve and an adjacent recipient denervated nerve stump significantly improves nerve regeneration after delayed nerve repair, the donor nerves sustaining the capacity of the denervated Schwann cells to support nerve regeneration. These reviewed methods to promote nerve regeneration and, in turn, to enhance functional recovery after nerve injury and surgical repair are sufficiently promising for early translation to the clinic.

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“…Studies of axonal regeneration in the sciatic nerve have shown that a conditioning lesion of the tibial nerve (a branch of the sciatic nerve) made 2 weeks before a sciatic nerve injury causes a significant increase in axon outgrowth. 40,41 Further work has shown that regeneration of dorsal root ganglion central processes into a peripheral nerve graft and regeneration of dorsal column fibers into a spinal cord lesion site is significantly improved by performing a peripheral nerve lesion. Thus, a preconditioning nerve lesion seems to increase the intrinsic regenerative ability of central axons by enhancing endogenous repair processes, such as elevation of intracellular cyclic adenosine monophosphate that allow axons to overcome myelin inhibition or by promoting of neuronal survival through attenuation of several injury-inducing mechanisms such as excitotoxicity, ion/pH imbalance, oxidative stress, metabolic dysfunction, and inflammation.…”

Section: -26mentioning

confidence: 99%

The Role of Diabetes Mellitus in the Clinical Presentation and Prognosis of Bell Palsy

Riga

Kefalidis

Danielides

2012

The Journal of the American Board of Family Medicine

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Background: Bell palsy is considered to be an entrapment neuropathy resulting from inflammation, edema, and strangulation. Diabetes, hypertension, and hypercholesterolemia have all been related to microangiopathies. However, the relationship between the frequency, severity, and recovery course of Bell palsy in patients with these pathologies is a matter of controversy.Methods: Fifty-six patients with Bell palsy were evaluated according to the House-Brackmann grading system a few days after the onset of the disease and 6 months later and correlated to their hypertension, hypercholesterolemia, and diabetes records. Diabetes was evaluated by the use of serum glycosylated hemoglobin (HbA1c).Results: The 20 patients with abnormal HbA1c values were more frequently diagnosed with Bell palsy of grade V/VI (P ‫؍‬ .008; odds ratio, 4.7; 95% CI, 1.4 -15.2). However, their House-Brackmann scores were not found to be worse at the 6-month follow-up visit (P ‫؍‬ .9). No correlations were found for hypertension and hypercholesterolemia.Conclusions: A relationship between the severity of Bell palsy and abnormal HbA1c values seems to be demonstrated. However, the prognosis of these patients does not seem to be worse because at the 6-month follow-up visit they present similar scores to nondiabetic patients. (J Am Board Fam Med 2012;25:819 -826.)

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Axonal regeneration in the rat sciatic nerve: Effect of a conditioning lesion and of dbcAMP

Cited by 285 publications

References 15 publications

PTEN Inhibition to Facilitate Intrinsic Regenerative Outgrowth of Adult Peripheral Axons

PTEN Inhibition to Facilitate Intrinsic Regenerative Outgrowth of Adult Peripheral Axons

Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans

The Role of Diabetes Mellitus in the Clinical Presentation and Prognosis of Bell Palsy

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