Axonal ion channels from bench to bedside: A translational neuroscience perspective

Krishnan, Arun V.; Lin, Cindy S.‐Y.; Park, Susanna B.; Kiernan, Matthew C.

doi:10.1016/j.pneurobio.2009.08.002

Cited by 150 publications

(138 citation statements)

References 352 publications

Supporting

Mentioning

134

Contrasting

Unclassified

Order By: Relevance

“…The resting membrane potential, depolarization and repolarization of axons are mediated by a series of voltage-gated sodium (Na V ) channels, potassium (K V ) channels, calcium channels and various ligand-gated channels (for example, transient receptor potential channels) 132 . In myelinated axons, the ion channels are clustered at the nodes of Ranvier to facilitate saltatory conduction, whereas in nonmyelinated axons, the channels are distributed diffusely and almost homogeneously along the axon 133,134 . Schwann cells are not excitable themselves, but do express ion channels that are involved in forming the nodal and paranodal regions where the neuronal ion channels are clustered, giving them the potential to influence axonal excitability.…”

Section: Microvascular Changes and Schwann Cells Microvascular Damagmentioning

confidence: 99%

Schwann cell interactions with axons and microvessels in diabetic neuropathy

et al. 2017

View full text Add to dashboard Cite

The incidence of diabetes mellitus has increased dramatically over the past two to three decades. According to the International Diabetes Federation Diabetes Atlas, 415 million people worldwide had diabetes in 2015, and this number is expected to grow by 5% annually, predominantly as a result of increasing prevalence of type 2 diabetes. Furthermore, an estimated 100 million Europeans and 80 million Americans have impaired glucose tolerance or prediabetes. Few people die from acute diabetes in countries with comprehensive health care systems, but the disease is inflicting a huge medical, social and economic burden on society owing to the need for lifelong treatment of its systemic consequences and the insidious development of multi-organ damage.Peripheral neuropathy (BOXES 1,2) is a common but often neglected complication of long-term diabetes, and the lack of treatment options reflects an incomplete understanding of the pathogenic mechanisms. Hyperglycaemia is generally accepted as the primary pathogenic insult in type 1 and type 2 diabetic neuropathy, although roles are emerging for other factors, such as impaired insulin signalling, hypertension and dyslipidaemia (particularly for type 2 diabetes), which might precede overt hyperglycaemia 1 . Many preclinical studies, and occasional clinical studies, have indicated that diabetic neuropathy -like diabetic nephropathy and retinopathy -results from microvascular disease, with a focus on axonal degeneration as a consequence of ischaemia and/or hypoxia. This mechanism, however, is likely to be only one aspect of a more complex pathogenesis.The earliest descriptions of pathology in diabetic neuropathy indicated that Schwannopathy accompanied axonal degeneration. The majority of clinical and basic research in diabetic neuropathy since then has focused on the effects on neurons. However, accumulating data from research into the development and regeneration of the PNS has identified Schwann cells as equally indispensable components that maintain neuronal structure and function, nourish axons, and promote survival and growth upon injury. The early reports from 1979 that demonstrated morphological changes in Schwann cells in human diabetic neuropathy 2 are now supported by an increased awareness of molecular alterations in Schwann cells during diabetes 3 . Schwann cells express a wide range of receptors and, when they sense insults or danger signals, they upregulate synthesis and secretion of factors that stimulate neuroprotection, regrowth and remyelination, or factors that aggravate disease phenotypes 4 . The most recent studies have demonstrated that Schwann cells regulate many aspects of axonal function, so that disruption of their metabolism by diabetes results in the accumulation of neurotoxic intermediates and compromises production of neuronal support factors, contributing to axonal degeneration, endothelial dysfunction and diabetic neuropathy. Abstract | The prevalence of diabetes worldwide is at pandemic levels, with the number of patients increasing by 5% annu...

show abstract

Section: Microvascular Changes and Schwann Cells Microvascular Damagmentioning

confidence: 99%

Schwann cell interactions with axons and microvessels in diabetic neuropathy

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The importance of ion channel subtypes will not be described in detail here, because extensive literature on this topic exists (Krishnan et al, 2009;Zamponi et al, 2009). As described above, sodium channels generate action potentials, and they can be seen as the accelerator of nociceptive messaging (Harvey and Dickenson, 2008).…”

Section: B Cellular and Receptor Levelmentioning

confidence: 99%

Human Experimental Pain Models for Assessing the Therapeutic Efficacy of Analgesic Drugs

et al. 2012

View full text Add to dashboard Cite

“…Although it has been reported that oxaliplatin-induced neurotoxicity is reversible upon treatment cessation [1,3,5], other reports suggest that oxaliplatin-induced neurotoxicity may be long lasting [6, 10,11]. Recently, axonal excitability studies [12,13] provided evidence for striking progressive changes in peripheral nerve function that developed across oxaliplatin treatment, predicting the development of neuropathy [6,8,14,15]. In the present study, prospective and longitudinal assessments of oxaliplatin-treated patients were undertaken to determine the extent to which oxaliplatin treatment induces long-standing alterations in peripheral nerve function.…”

Section: Introductionmentioning

confidence: 99%

Long-Term Neuropathy After Oxaliplatin Treatment: Challenging the Dictum of Reversibility

et al. 2011

Self Cite

View full text Add to dashboard Cite

After completing this course, the reader will be able to:1. Define the symptoms of sensory neurotoxicity in oxaliplatin-treated patients and identify the long-term natural history of nerve dysfunction as a long-lasting complication of treatment that does not necessarily resolve within 6 months.2. Use sensory excitability techniques to predict long-standing changes in sensory nerve function produced by oxaliplatin.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTObjectives. Oxaliplatin-induced neuropathy is a significant and dose-limiting toxicity that adversely affects quality of life. However, the long-term neurological sequelae have not been adequately described. The present study aimed to describe the natural history of oxaliplatin-induced neuropathy, using subjective and objective assessments. The Oncologist CME Program is located online at http://cme.theoncologist.com/. To take the CME activity related to this article, you must be a registered user. Methods. From a population of 108 oxaliplatin-treated Symptom Management and Supportive CareThe Oncologist 2011;16:708 -716 www.TheOncologist.com Results. At follow-up, 79.2% of patients reported residual neuropathic symptoms, with distal loss of pinprick sensibility in 58.3% of patients and loss of vibration sensibility in 83.3% of patients. Symptom severity scores were significantly correlated with cumulative dose. There was no recovery of sensory action potential amplitudes in upper and lower limbs, consistent with persistent axonal sensory neuropathy. Sensory excitability parameters had not returned to baseline levels, suggesting persisting abnormalities in nerve function. The extent of excitability abnormalities during treatment was significantly correlated with clinical outcomes at follow-up.Conclusions. These findings establish the persistence of subjective and objective deficits in oxaliplatin-treated patients post-oxaliplatin, suggesting that sensory neuropathy is a long-term outcome, thereby challenging the literature on the reversibility of oxaliplatin-induced neuropathy. The Oncologist 2011;16:708 -716

show abstract

Axonal ion channels from bench to bedside: A translational neuroscience perspective

Cited by 150 publications

References 352 publications

Schwann cell interactions with axons and microvessels in diabetic neuropathy

Schwann cell interactions with axons and microvessels in diabetic neuropathy

Human Experimental Pain Models for Assessing the Therapeutic Efficacy of Analgesic Drugs

Long-Term Neuropathy After Oxaliplatin Treatment: Challenging the Dictum of Reversibility

Contact Info

Product

Resources

About