Jason R Plemel

Jason R Plemel
University of Alberta | UAlberta · Division of Neurology

Ph.D.
Husband, Father, and Assistant Prof @UAlberta_FoMD. Studying in all things glia.

About

51
Publications
12,580
Reads
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3,214
Citations
Introduction
Dr. Plemel and his laboratory will investigate how microglia play an important role in the regeneration of injured white matter, but also how microglia can induce injury to white matter during different disease conditions.
Additional affiliations
June 2018 - present
University of Alberta
Position
  • Professor (Assistant)
January 2013 - May 2018
The University of Calgary
Position
  • PostDoc Position
August 2012 - December 2012
University of British Columbia - Vancouver
Position
  • PostDoc Position
Education
September 2005 - August 2012

Publications

Publications (51)
Article
Full-text available
Background The dietary consumption of cuprizone – a copper chelator – has long been known to induce demyelination of specific brain structures and is widely used as model of multiple sclerosis. Despite the extensive use of cuprizone, the mechanism by which it induces demyelination are still unknown. With this review we provide an updated understand...
Preprint
Full-text available
Multiple Sclerosis (MS) is an autoimmune disease with notable sex differences. Women are not only more likely to develop MS but are also more likely than men to experience neuropathic pain in the disease. It has been postulated that neuropathic pain in MS can originate in the peripheral nervous system at the level of the dorsal root ganglia (DRG),...
Preprint
Multiple Sclerosis (MS) is an autoimmune disease with notable sex differences. Women are not only more likely to develop MS but are also more likely than men to experience neuropathic pain in the disease. It has been postulated that neuropathic pain in MS can originate in the peripheral nervous system at the level of the dorsal root ganglia (DRG),...
Preprint
Social isolation is a profound form of psychological stress that impacts the mental health of a large proportion of society. Other experimental models of stress and injury have demonstrated microglia activation and alterations in neural activity. Microglia and neural activity undergo coordinated changes under physiological and pathological states....
Article
Full-text available
There are over 15 disease-modifying drugs that have been approved over the last 20 years for the treatment of relapsing–remitting multiple sclerosis (MS), but there are limited treatment options available for progressive MS. The development of new drugs for the treatment of progressive MS remains challenging as the pathophysiology of progressive MS...
Article
Full-text available
Background CD33 is genetically linked to Alzheimer’s disease (AD) susceptibility through differential expression of isoforms in microglia. The role of the human CD33 short isoform (hCD33m), preferentially encoded by an AD-protective CD33 allele (rs12459419T), is unknown. Here, we test whether hCD33m represents a loss-of-function or gain-of-function...
Article
Full-text available
Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system (CNS). Repair through remyelination can be extensive, but quantification of remyelination remains challenging. To date, no method for standardized digital quantification of remyelination of MS lesions exists. This methodological study aims to pres...
Article
The dynamic expansions and contractions of the microglia population in the central nervous system (CNS) to achieve homeostasis are likely vital for their function. Microglia respond to injury or disease but also help guide neurodevelopment, modulate neural circuitry throughout life, and direct regeneration. Throughout these processes, microglia den...
Article
With substantial progress in experimental therapeutics to enhance the nervous system’s capacity for remyelination, new methods to detect myelin are important advances. We discuss a small-angle X-ray scattering tensor tomography approach presented recently by Georgiadis et al. and the method’s promise in providing a new window into the brain to eval...
Article
Full-text available
Multiple Sclerosis (MS) is a neurodegenerative disease characterized by multiple focal lesions, ongoing demyelination and, for most people, a lack of remyelination. MS lesions are enriched with monocyte-derived macrophages and brain-resident microglia that, together, are likely responsible for much of the immune-mediated neurotoxicity. However, mic...
Article
Age is a critical risk factor for many neurologic conditions, including progressive multiple sclerosis. Yet the mechanisms underlying the relationship are unknown. Using lysolecithin-induced demyelinating injury to the mouse spinal cord, we characterized the acute lesion and investigated the mechanisms of increased myelin and axon damage with age....
Article
Full-text available
Remyelination following CNS demyelination restores rapid signal propagation and protects axons; however, its efficiency declines with increasing age. Both intrinsic changes in the oligodendrocyte progenitor cell population and extrinsic factors in the lesion microenvironment of older subjects contribute to this decline. Microglia and monocyte-deriv...
Article
Full-text available
The article Niacin‑mediated rejuvenation of macrophage/microglia enhances remyelination of the aging central nervous system, written by Khalil S. Rawji, Adam M.H. Young, Tanay Ghosh, Nathan J. Michaels, Reza Mirzaei, Janson Kappen, Kathleen L. Kolehmainen, Nima Alaeiilkhchi, Brian Lozinski, Manoj K. Mishra, Annie Pu, Weiwen Tang, Salma Zein, Deepak...
Article
Full-text available
Microglia and infiltrating macrophages are thought to orchestrate the central nervous system (CNS) response to injury; however, the similarities between these cells make it challenging to distinguish their relative contributions. We genetically labeled microglia and CNS-associated macrophages to distinguish them from infiltrating macrophages. Using...
Article
Full-text available
In diseases such as multiple sclerosis (MS), inflammation can injure the myelin sheath that surrounds axons, a process known as demyelination. The spontaneous regeneration of myelin, called remyelination, is associated with restoration of function and prevention of axonal degeneration. Boosting remyelination with therapeutic intervention is a promi...
Article
Oligodendrocyte progenitor cells (OPCs) are the most proliferative and dispersed population of progenitor cells in the adult central nervous system, which allows these cells to rapidly respond to damage. Oligodendrocytes and myelin are lost after traumatic spinal cord injury (SCI), compromising efficient conduction and, potentially, the long‐term h...
Article
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that involves demyelination and axonal degeneration. Although substantial progress has been made in drug development for relapsing-remitting MS, treatment of the progressive forms of the disease, which are characterized clinically by the accumulation of disabili...
Article
Full-text available
Remyelination occurs after spinal cord injury (SCI) but its functional relevance is unclear. We assessed the necessity of myelin regulatory factor (Myrf) in remyelination after contusive SCI by deleting the gene from platelet-derived growth factor receptor alpha positive (PDGFRα-positive) oligodendrocyte progenitor cells (OPCs) in mice prior to SCI...
Article
Full-text available
Although immune attack against central nervous system (CNS) myelin is a central feature of multiple sclerosis (MS), its root cause is unresolved. In this report, we provide direct evidence that subtle biochemical modifications to brain myelin elicit pathological immune responses with radiological and histological properties similar to MS lesions. A...
Article
Aging impairs regenerative processes including remyelination, the synthesis of a new myelin sheath. Microglia and other infiltrating myeloid cells such as macrophages are essential for remyelination through mechanisms that include the clearance of inhibitory molecules within the lesion. Prior studies have shown that the quantity of myeloid cells an...
Research
Full-text available
Multiple sclerosis (MS) is a chronic inflammatory disease that, for most people, ultimately transitions into a progressive neurodegenerative condition referred to as progressive MS. According to the national MS society, there are currently 16 FDA approved medications for the treatment of MS which may give the impression that MS is a treatable disea...
Article
It is widely recognized that myelination of axons greatly enhances the speed of signal transmission. An exciting new finding is the dynamic communication between axons and their myelin-forming oligodendrocytes, including activity-dependent signalling from axon to myelin. The oligodendrocyte–myelin complex may in turn respond by providing metabolic...
Article
For decades lysophosphatidylcholine (LPC, lysolecithin) has been used to induce demyelination, without a clear understanding of its mechanisms. LPC is an endogenous lysophospholipid so it may cause demyelination in certain diseases. We investigated whether known receptor systems, inflammation or nonspecific lipid disruption mediates LPC-demyelinati...
Article
Full-text available
Remyelination is limited in the majority of multiple sclerosis (MS) lesions despite the presence of oligodendrocyte precursor cells (OPCs) in most lesions. This observation has led to the view that a failure of OPCs to fully differentiate underlies remyelination failure. OPC differentiation requires intricate transcriptional regulation, which may b...
Article
Spontaneous remyelination occurs after spinal cord injury (SCI), but the extent of myelin repair and identity of the cells responsible remain incompletely understood and contentious. We assessed the cellular origin of new myelin by fate mapping PDGFRα+, Olig2+, and P0+ cells following contusion SCI in mice. Oligodendrocyte precursor cells (OPCs; PD...
Article
Multiple sclerosis is characterized by inflammatory activity that results in destruction of the myelin sheaths that enwrap axons. The currently available medications for multiple sclerosis are predominantly immune-modulating and do not directly promote repair. White matter regeneration, or remyelination, is a new and exciting potential approach to...
Article
Spinal cord injury can lead to severe motor, sensory and autonomic dysfunction. Currently, there is no effective treatment for the injured spinal cord. The transplantation of Schwann cells, neural stem cells or progenitor cells, olfactory ensheathing cells, oligodendrocyte precursor cells and mesenchymal stem cells has been investigated as potentia...
Article
Full-text available
Cellular injury and death are ubiquitous features of disease, yet tools to detect them are limited and insensitive to subtle pathological changes. Acridine orange (AO), a nucleic acid dye with unique spectral properties, enables real-time measurement of RNA and DNA as proxies for cell viability during exposure to various noxious stimuli. This tool...
Article
Full-text available
Remyelination is the generation of new myelin sheaths after injury facilitated by processes of differentiating oligodendrocyte precursor cells (OPCs). Although this repair phenomenon occurs in lesions of multiple sclerosis patients, many lesions fail to completely remyelinate. A number of factors have been identified that contribute to remyelinatio...
Data
Supplementary Figures 1-11, Supplementary Tables 1-3 and Supplementary Methods.
Article
Myelinated axons efficiently transmit information over long distances. The apposed myelin sheath confers favorable electrical properties, but restricts access of the axon to its extracellular milieu. Therefore, axonal metabolic support may require specific axo-myelinic communication. Here we explored activity-dependent glutamate-mediated signaling...
Article
Full-text available
Anti-oxidant compounds that are found in over-the-counter (OTC) supplements and foods are gaining interest as treatments for multiple sclerosis (MS). They are widely used by patients, sometimes without a clear evidence base. We conducted a systematic review of animal and clinical research to determine the evidence for the benefits of OTC anti-oxida...
Article
Historically, the immune response after spinal cord injury was considered largely detrimental owing to the release of neurotoxic factors. While there is validity to this view, there is much greater heterogeneity of immune cells than was previously realized. Associated with this heterogeneity of immune cell subtypes, there is diversity of functions...
Article
Full-text available
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...
Article
Myelin loss is a hallmark of multiple sclerosis (MS) and promoting central nervous system myelin repair has become a major therapeutic target. Despite the presence of oligodendrocytes precursors cells (OPCs) in chronic lesions of MS, remyelination often fails. The mechanism underlying this failure of remyelination remains unknown, but it is hypothe...
Article
Full-text available
Remyelination following spinal cord injury (SCI) is thought to be incomplete; demyelination is reported to persist chronically and is proposed as a compelling therapeutic target. Yet most reports do not distinguish between the myelin status of intact axons and injury-severed axons whose proximal stumps persist but provide no meaningful function. We...
Article
Spinal cord injury (SCI) results in substantial oligodendrocyte death and subsequent demyelination leading to white-matter defects. Cell replacement strategies to promote remyelination are under intense investigation; however, the optimal cell for transplantation remains to be determined. We previously isolated a platelet-derived growth factor (PDG...
Article
Full-text available
Spinal cord injury (SCI) often results in a loss of motor and sensory function. Currently there are no validated effective clinical treatments. Previously we found in rats that dietary restriction, in the form of every-other-day fasting (EODF), started prior to (pre-EODF), or after (post-EODF) an incomplete cervical SCI was neuroprotective, increas...
Article
Previously, we reported that every-other-day-fasting (EODF) in Sprague-Dawley rats initiated after cervical spinal cord injury (SCI) effectively promoted functional recovery, reduced lesion size, and enhanced sprouting of the corticospinal tract. More recently, we also showed improved behavioral recovery with EODF after a moderate thoracic contusio...
Article
The failure of CNS axons to regenerate following traumatic injury is due in part to a growth-inhibitory environment in CNS as well as a weak intrinsic neuronal growth response. Olfactory ensheathing cell (OECs) transplants have been reported to create a favorable environment promoting axonal regeneration, remyelination, and functional recovery afte...
Article
Full-text available
Cell transplantation therapies have become a major focus in pre-clinical research as a promising strategy for the treatment of spinal cord injury (SCI). In this article, we systematically review the available pre-clinical literature on the most commonly used cell types in order to assess the body of evidence that may support their translation to hu...
Article
Full-text available
Given the rising availability and use of genetically modified animals in basic science research, it has become increasingly important to develop clinically relevant models for spinal cord injury (SCI) for use in mice. We developed a graded forceps crush model of SCI in mice that uses three different forceps with spacers of 0.25, 0.4, and 0.55 mm, t...
Article
Full-text available
Transplantation of exogenous cells is one approach to spinal cord repair that could potentially enhance the growth and myelination of endogenous axons. Here, we asked whether skin-derived precursors (SKPs), a neural crest-like precursor that can be isolated and expanded from mammalian skin, could be used to repair the injured rat spinal cord. To as...

Questions

Question (1)
Question
Is anyone aware of a paper where cuprizone is injected into the brain or spinal cord? I was just wondering if it was possible to induce local demyelination this way.

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Projects (3)