Check out some of the papers that were recently published by DMCBH members:

Anthony Traboulsee, Shannon Kolind: Ocrelizumab-treated patients with relapsing multiple sclerosis show volume loss rates similar to healthy aging

Journal: Multiple Sclerosis Journal

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by two major and interconnected hallmarks: inflammation and progressive neurodegeneration. The aim of this work was to compare neurodegenerative processes, in the form of global and regional brain volume loss rates, in healthy controls (HCs) and in patients with relapsing MS treated with ocrelizumab, which suppresses acute inflammation.

Ocrelizumab-treated patients showed global and regional brain volume loss rates that were approaching that of HCs. These findings are consistent with an important role of inflammation on overall tissue loss and the role of ocrelizumab in reducing this phenomenon.

Cornelia Laule, Piotr Kozlowski, Erin MacMillan, Irene Vavasour:
Myelin biomarkers in the healthy adult brain: Correlation, reproducibility, and the effect of fiber orientation

Journal: Magnetic Resonance in Medicine

This study investigated the correlation, reproducibility, and effect of white matter fiber orientation for three myelin-sensitive MRI techniques: magnetization transfer ratio (MTR), inhomogeneous magnetization transfer ratio (ihMTR), and gradient and spin echo–derived myelin water fraction (MWF). The three metrics were measured in 17 white and three deep grey matter regions in 17 healthy adults.

Results revealed a strong correlation between ihMTR and MTR, and ihMTR and MWF. All three metrics varied with fiber direction. However, separating the apparent orientation dependence by white matter region revealed large dissimilarities in the trends, suggesting that real differences in myelination between regions are confounding the apparent orientation dependence measured using this method. The strong correlation between ihMTR and MWF suggests that these techniques are measuring the same myelination; however, the larger dynamic range of MWF may provide more power to detect small differences in myelin.

Anthony Phillips, Terry Snutch:
Morphine withdrawal-induced hyperalgesia in models of acute and extended withdrawal is attenuated by l-Tetrahydropalmatine

Journal: International Journal of Molecular Sciences

Effective pain control is an underappreciated aspect of managing opioid withdrawal, and its absence presents a significant barrier to successful opioid detoxification. Accordingly, there is an urgent need for effective non-opioid treatments to facilitate opioid detoxification. l-Tetrahydropalmatine (l-THP) possesses powerful analgesic properties and is an active ingredient in botanical formulations used in Vietnam for the treatment of opioid withdrawal syndrome.

In this study, rats receiving morphine displayed a progressive increase in pain thresholds during acute withdrawal. A single dose of l-THP administered during the 4th and 5th weeks of morphine treatment significantly improves pain tolerance scores. A 7-day course of l-THP treatment in animals experiencing extended withdrawal significantly attenuates hyperalgesia and reduces the number of days to recovery to baseline pain thresholds by 61%. This indicates that the efficacy of l-THP on pain perception extends beyond its half-life. As a non-opioid treatment for reversing a significant hyperalgesic state during withdrawal, l-THP may be a valuable addition to the currently limited arsenal of opioid detoxification treatments.

Annie Ciernia, Brian MacVicar:
Modelling microglial innate immune memory in vitro: Understanding the role of aerobic glycolysis in innate immune memory 

Journal: International Journal of Molecular Sciences

Microglia, the resident macrophages of the central nervous system, play important roles in maintaining brain homeostasis and facilitating the brain’s innate immune responses. Following immune challenges, microglia also retain immune memories, which can alter responses to secondary inflammatory challenges. Microglia have two main memory states, training and tolerance, which are associated with increased and attenuated expression of inflammatory cytokines. However, the mechanisms differentiating these two distinct states are not well understood.

The research team investigated mechanisms underlying training versus tolerance memory paradigms in vitro using B-cell-activating factor (BAFF) or bacterial lipopolysaccharide (LPS) as a priming stimulus followed by LPS as a second stimulus. BAFF followed by LPS showed enhanced responses indicative of priming. LPS followed by LPS as the second stimulus caused reduced responses suggestive of tolerance. Inhibiting aerobic glycolysis during the priming stimulus prevented the establishment of the tolerized memory state. The researchers conclude that aerobic glycolysis triggered by the first LPS stimulus was a critical step in the induction of innate immune tolerance.

Noah Silverberg:
The American Congress of Rehabilitation Medicine diagnostic criteria for mild traumatic brain injury

Journal: Archives of Physical Medicine and Rehabilitation

The objective was to develop new diagnostic criteria for mild traumatic brain injury (TBI) that are appropriate for use across the lifespan and in sports, civilian trauma, and military settings. The new diagnostic criteria was developed through an evidence review and expert consensus process. The group convened a working group of 17 members and an external interdisciplinary expert panel of 32 clinician-scientists. Public stakeholder feedback was analyzed from 68 individuals and 23 organizations. Having unified diagnostic criteria for mild TBI will improve the quality and consistency of mild TBI research and clinical care.

Wilfred Jefferies:
Specific cannabinoids revive adaptive immunity by reversing immune evasion mechanisms in metastatic tumours

Journal: Frontiers in Immunology

Immune subversion by metastatic tumours can be achieved through several mechanisms; one of the most frequently observed involves the loss of expression or mutation of genes composing the MHC-I antigen presentation machinery that yields tumours invisible to Cytotoxic T lymphocytes, the key component of the adaptive cellular immune response. Findings indicate that cannabinoids inhibit the growth and progression of several categories of cancer; however, the mechanisms underlying these observations remain clouded in uncertainty.

Here, the researchers screened a library of cannabinoid compounds and found molecular selectivity amongst specific cannabinoids, where related molecules can reverse the metastatic immune escape phenotype in vitro by inducing MHC-I cell surface expression in metastatic tumours that subsequently sensitize tumours to T lymphocyte recognition. Overall, the data suggest that specific cannabinoids may have utility in cancer immunotherapy regimens by overcoming immune escape and augmenting cancer immune surveillance in metastatic disease.

Judy Illes:
Engaging with Indigenous communities in brain science: not only the what, but the way

Journal: The Canadian Journal of Neurological Sciences

This study explores how incorporating Indigenous methodologies can help the neurological sciences community in a way that centers Indigenous knowledge. The research team brought together Indigenous methodologies and Western approaches to create a 20-member Indigenous brain wellness and mental health working group.

The team found the need to reaffirm holistic conceptualizations of brain wellness and mental health, integrate Indigenous and Western healing approaches, pursue systems and community-level changes to overcome the continuing health impacts of racism and colonization, and regain connections with culture and spirit. Indigenous methodologies can help researchers to break away from the status quo of Western thinking in neuroscience and work in a way that is ethically grounded, sustainable, and transformative.

Weihong Song
: USP25 contributes to defective neurogenesis and cognitive impairments

Journal: Federation of American Societies for Experimental Biology

Both Down syndrome (DS) individuals and animal models exhibit hypo-cellularity in hippocampus indicated by enhanced neuronal death and compromised neurogenesis. Ubiquitin-specific peptidase 25 (USP25), a human chromosome 21 gene, encodes for a deubiquitinating enzyme overexpressed in DS patients. Dysregulation of USP25 has been associated with Alzheimer’s phenotypes in DS, but its role in defective neurogenesis in DS has not been defined.

In this study, the researchers found that USP25 upregulation impaired cell cycle regulation during embryonic neurogenesis and cortical development. Overexpression of USP25 in hippocampus reduced neurogenesis. USP25-Tg mice showed increased anxiety/depression-like behaviors and learning and memory deficits. These results suggested that USP25 overexpression resulted in defective neurogenesis and cognitive impairments, which could contribute to the pathogenesis of DS. USP25 may be a potential pharmaceutical target for DS.

Judy Illes:
Mapping the landscape of equitable access to advanced neurotechnologies in Canada

Journal: The Canadian Journal of Neurological Sciences

Geographic, social, political, and economic factors shape access to advanced neurotechnologies, yet little previous research has explored the barriers and areas of opportunity for equitable access for diverse patient communities across Canada. This study applied a mixed-model approach to consult with 24 medical experts who are involved in the care of patients who undergo functional neurosurgery targeting the brain.

Descriptive statistics suggest that interviewees perceive a disparity between the imperative of access to advanced neurotechnologies for people living in rural and remote areas and the likelihood of achieving such access. The results depict a complex picture of access to functional neurosurgery in Canada with a motivation to improve the availability of care for vulnerable populations through the expansion of distributed care models, improved health care system efficiencies, increasing funding and support for patient travel, and increasing awareness about and advocacy for advanced neurotechnologies.

Khaled Abdelrahman:
VGLUT3 deletion rescues motor deficits and neuronal loss in the zQ175 mouse model of Huntington’s disease

Journal: Journal of Neuroscience

Huntington’s disease (HD) is an autosomal-dominant neurodegenerative disease characterized by progressive motor and cognitive impairments, with no disease-modifying therapies yet available. The vesicular glutamate transporter-3 (VGLUT3) regulates the striatal network that is centrally affected by HD. Nevertheless, current evidence on the role of VGLUT3 in HD pathophysiology is lacking.

Here, the researchers crossed mice lacking Slc17a8 gene with heterozygous knock-in mouse model of HD. Longitudinal assessment of motor and cognitive functions reveals that VGLUT3 deletion rescues motor coordination, neuronal loss, and short-term memory deficits in mice. These findings provide novel evidence that VGLUT3, despite its limited expression, can be a vital contributor to HD pathophysiology and a viable target for HD therapeutics.

Mypinder Sekhon:
A brain-based definition of death and criteria for its determination after arrest of circulation or neurologic function in Canada: a 2023 clinical practice guideline

Journal: Canadian Journal of Anaesthesia

This 2023 Clinical Practice Guideline provides the biomedical definition of death based on permanent cessation of brain function that applies to all persons, as well as recommendations for death determination by circulatory criteria for potential organ donors and death determination by neurologic criteria for all mechanically ventilated patients regardless of organ donation potential.