Brett J Hilton

Brett J Hilton
University of British Columbia - Vancouver | UBC · Department of Cellular and Physiological Sciences

PhD

About

23
Publications
6,872
Reads
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1,403
Citations
Citations since 2017
12 Research Items
1319 Citations
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Introduction
My goals are to understand why nerve cells don't regenerate after brain or spinal cord injury and to develop effective strategies to regenerate and rewire lost circuits following injury or disease.
Additional affiliations
April 2017 - present
Deutsches Zentrum für Neurodegenerative Erkrankungen
Position
  • Fellow
January 2017 - March 2017
University of British Columbia - Vancouver
Position
  • Fellow
September 2010 - December 2016
University of British Columbia - Vancouver
Position
  • PhD Student
Description
  • Regeneration and plasticity of descending motor pathways following spinal cord injury.
Education
September 2010 - May 2016
University of British Columbia - Vancouver
Field of study
  • Zoology (Neuroscience)
September 2005 - November 2010
University of British Columbia - Vancouver
Field of study
  • Cell Biology & Genetics
September 2005 - November 2010
University of British Columbia - Vancouver
Field of study
  • English Literature

Publications

Publications (23)
Article
Full-text available
In the adult mammalian central nervous system (CNS), neurons typically fail to regenerate their axons after injury. During development, by contrast, neurons extend axons effectively. A variety of intracellular mechanisms mediate this difference, including changes in gene expression, the ability to form a growth cone, differences in mitochondrial fu...
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
Unlabelled: Motor cortical plasticity contributes to spontaneous recovery after incomplete spinal cord injury (SCI), but the pathways underlying this remain poorly understood. We performed optogenetic mapping of motor cortex in channelrhodopsin-2 expressing mice to assess the capacity of the cortex to re-establish motor output longitudinally after...
Article
Full-text available
How aging impacts axon regeneration after CNS injury is not known. We assessed the impact of age on axon regeneration induced by Pten deletion in corticospinal and rubrospinal neurons, two neuronal populations with distinct innate regenerative abilities. As in young mice, Pten deletion in older mice remains effective in preventing axotomy-induced d...
Article
Full-text available
Axons in the adult mammalian central nervous system fail to regenerate after spinal cord injury. Neurons lose their capacity to regenerate during development, but the intracellular processes underlying this loss are unclear. We found that critical components of the presynaptic active zone prevent axon regeneration in adult mice. Transcriptomic anal...
Article
Full-text available
An inhibitory extracellular milieu and neuron-intrinsic processes prevent axons from regenerating in the adult central nervous system (CNS). Here we show how the two aspects are interwoven. Genetic loss-of-function experiments determine that the small GTPase RhoA relays extracellular inhibitory signals to the cytoskeleton by adapting mechanisms set...
Article
In this issue of Neuron, Wang et al. demonstrate that both cell-intrinsic and -extrinsic factors restrict the myelination of newly regenerated axons. Pharmalogical targeting of GPR17 signaling in oligodendrocyte precursor cells (OPCs) and microglial inhibition of oligodendrocyte maturation together promote robust myelination of regenerated axons af...
Article
Full-text available
The specification of an axon and its subsequent outgrowth are key steps during neuronal polarization, a prerequisite to wire the brain. The Rho-guanosine triphosphatase (GTPase) RhoA is believed to be a central player in these processes. However, its physiological role has remained undefined. Here, genetic loss- and gain-of-function experiments com...
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
Injured axons fail to regenerate in the adult CNS, which contrasts with their vigorous growth during embryonic development. We explored the potential of re-initiating axon extension after injury by reactivating the molecular mechanisms that drive morphogenetic transformation of neurons during development. Genetic loss- and gain-of-function experime...
Article
Here we present a protocol for analyses of axon regeneration and density in unsectioned adult mouse spinal cord. This includes methods for injury and tracing of dorsal column sensory and corticospinal axons; clearing and staining of unsectioned spinal cord; visualization of axon degeneration and regeneration in cleared and uncleared specimens using...
Article
Axons in the adult mammalian brain and spinal cord fail to regenerate upon lesion. In vivo imaging serves as a tool to investigate the immediate response of axons to injury and how the same injured axons behave over time. Here, we describe the dynamic changes that injured sensory axons undergo and methods of imaging them in vivo. First, we explain...
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
Spinal cord injury disrupts connectivity between the brain and the body. With electrochemical neuromodulation and intensive rehabilitation training, the cortex can functionally connect with spinal circuits below injury by relaying signals through the brainstem.
Article
Full-text available
Spinal cord injury (SCI) in the mammalian CNS results in the formation of a glial scar around the lesion site ([Fig. 1][1] A ). The scar limits axon regeneration but it also serves a protective role by sequestering inflammatory cells to the lesion center, reducing tissue damage ([Herrmann et al.,
Article
Full-text available
We evaluated the effects of ministrokes targeted to individual pial arterioles on motor function in Thy-1 line 18 channelrhodopsin-2 (ChR2) transgenic mice within the first hours after ischemia. Using optogenetics, we directly assessed both the excitability and motor output of cortical neurons in a manner independent of behavioral state or training...
Article
Full-text available
High fat, low carbohydrate ketogenic diets (KD) are validated non-pharmacological treatments for some forms of drug-resistant epilepsy. Ketones reduce neuronal excitation and promote neuroprotection. Here, we investigated the efficacy of KD as a treatment for acute cervical spinal cord injury (SCI) in rats. Starting 4 hours following C5 hemi-contus...
Article
Full-text available
Though upper extremity functional recovery is a high priority for spinal cord injured patients with cervical injuries, few injury models have been developed in mice with sustained deficits in forelimb motor function. Here we characterize a dorsolateral funiculus crush model in mice, which ablates the rubrospinal tract unilaterally and thus allows c...
Article
Full-text available
The limited potential for regeneration and plasticity of adult mammalian CNS axons is a major impediment to functional recovery following spinal cord injury (SCI). Inhibitory extracellular matrix, particularly chondroitin sulfate proteoglycans (CSPGs), associated with the lesion penumbra and
Conference Paper
Background: The paralysis that occurs following spinal cord injury (SCI) is largely the result of transected central nervous system (CNS) axons failing to regenerate. Previous research has indicated that a major contributor to this regenerative failure is a diminished intrinsic capacity of adult CNS axons to grow, based largely on inactivity in the...
Article
Full-text available
This study investigates wasting disease in the northeast Pacific keystone predatory sea star Pisaster ochraceus on the outer west coast of Vancouver Island (British Columbia, Canada). To quantify the effects of temperature, season and locality on the vulnerability of P. ochraceus to wasting disease, we conducted surveys and experiments in early and...

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