Background The fastest-growing neurological disorder is Parkinson disease (PD), a progressive neurodegenerative disease that affects 10 million people worldwide. PD is typically treated with levodopa, an oral pill taken to increase dopamine levels, and other dopaminergic agonists. As the disease advances, the efficacy of the drug diminishes, necessitating adjustments in treatment dosage according to the patient’s symptoms and disease progression. Therefore, remote monitoring systems that can provide more detailed and accurate information on a patient’s condition regularly are a valuable tool for clinicians and patients to manage their medication. The Parkinson’s Remote Interactive Monitoring System (PRIMS), developed by PragmaClin Research Inc, was designed on the premise that it will be an easy-to-use digital system that can accurately capture motor and nonmotor symptoms of PD remotely. Objective We performed a usability evaluation in a simulated clinical environment to assess the ease of use of the PRIMS and determine whether the product offers suitable functionality for users in a clinical setting. Methods Participants were recruited from a user sign-up web-based database owned by PragmaClin Research Inc. A total of 11 participants were included in the study based on the following criteria: (1) being diagnosed with PD and (2) not being diagnosed with dementia or any other comorbidities that would make it difficult to complete the PRIMS assessment safely and independently. Patient users completed a questionnaire that is based on the Movement Disorder Society–sponsored revision of the Unified Parkinson’s Disease Rating Scale. Interviews and field notes were analyzed for underlying themes and topics. Results In total, 11 people with PD participated in the study (female individuals: n=5, 45%; male individuals: n=6, 55%; age: mean 66.7, SD 7.77 years). Thematic analysis of the observer’s notes revealed 6 central usability issues associated with the PRIMS. These were the following: (1) the automated voice prompts are confusing, (2) the small camera is problematic, (3) the motor test exhibits excessive sensitivity to the participant’s orientation and position in relation to the cameras, (4) the system poses mobility challenges, (5) navigating the system is difficult, and (6) the motor test exhibits inconsistencies and technical issues. Thematic analysis of qualitative interview responses revealed four central themes associated with participants’ perspectives and opinions on the PRIMS, which were (1) admiration of purpose, (2) excessive system sensitivity, (3) video instructions preferred, and (4) written instructions disliked. The average system usability score was calculated to be 69.2 (SD 4.92), which failed to meet the acceptable system usability score of 70. Conclusions Although multiple areas of improvement were identified, most of the participants showed an affinity for the overarching objective of the PRIMS. This feedback is being used to upgrade the current PRIMS so that it aligns more with patients’ needs.

Background Assessing the impact of cannabis on cognitive and physical performance is imperative, especially in safety-sensitive environments. This study investigated the degree and duration of performance impairment after cannabis consumption. Methods Fourteen cannabis users were subjected to physical and cognitive testing before and after smoking cannabis. Tests included assessment of intoxication, vital signs, psychomotor abilities, and muscle function. Blood, urine and saliva were analyzed for Delta-9-tetrahydrocannabinol (THC) and Carboxy-THC at baseline, and 1-, 6-, and 12-hours post-consumption. Results Blood THC levels peaked significantly at 1 hour and declined by 6 hours (p < 0.001), whereas Carboxy-THC levels showed a less pronounced but consistent variation over time (p = 0.005). Urine Carboxy-THC levels displayed a non-significant similar trend (p = 0.068). Acute cannabis use significantly (p = 0.01 – p < 0.001) raised systolic blood pressure and heart rate, increased force variability, reduced rate of force development, and compromised balance and muscle endurance up to 12 hours post-consumption. Conclusions Acute cannabis consumption results in physical impairments, impacting essential functions required for safety-sensitive tasks. The sustained presence of Carboxy-THC indicates prolonged pharmacological effects and necessitates cautious policy-making for workplaces. Trial Registration This study was not registered as a clinical trial as the ClinicalTrials.gov indicates that the study must answer yes to all four questions on their checklist. Although, our study was interventional, it was not conducted in the US nor involved a new FDA investigational new drug application, and the cannabis was not manufactured or exported from the US. The focus of the study was on the recreational use of a single cannabis cigarette on subsequent physiological or work performance and safety measures over 12 hours.

There are many different types of berry-producing plants that grow throughout North America. These various species of plants produce berries, known by their common names, such as blueberry, lingonberry, cranberry, crowberry, blackberry, bunchberry, bearberry, and strawberry. The berry fruits are important food sources and can be eaten fresh or preserved. The leaves of several species can also be enjoyed in teas. Contemporary medicine has demonstrated many potential health benefits of berries due to their antioxidant and anti-inflammatory activity. Indigenous Peoples have not only utilized berries as food, likely over many centuries, but have also passed down knowledge on the medicinal uses of various parts of these plants including the fruits, leaves and roots. This short review provides a synopsis of some of the major species of berry producing plants that are prevalent in Canada, particularly eastern Canada. Current knowledge and traditional uses of important species of berry-producing plants are discussed.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by a loss of dopaminergic neurons, leading to bradykinesia, rigidity, tremor at rest, and postural instability, as well as non-motor symptoms such as olfactory impairment, pain, autonomic dysfunction, impaired sleep, fatigue, and behavioral changes. The pathogenesis of PD is believed to involve oxidative stress, disruption to mitochondria, alterations to the protein α-synuclein, and neuroinflammatory processes. There is currently no cure for the disease. Polyphenols are secondary metabolites of plants, which have shown benefit in several experimental models of PD. Intake of polyphenols through diet is also associated with lower PD risk in humans. In this review, we provide an overview of the pathology of PD and the data supporting the potential neuroprotective capacity of increased polyphenols in the diet. Evidence suggests that the intake of dietary polyphenols may inhibit neurodegeneration and the progression of PD. Polyphenols appear to have a positive effect on the gut microbiome, which may decrease inflammation that contributes to the disease. Therefore, a diet rich in polyphenols may decrease the symptoms and increase quality of life in PD patients.

BACKGROUND:The recent legalization of cannabis use in Canada requires pharmacists to be able to support their patients with accurate knowledge of its known risks and benefits. Certain populations, such as pregnant and breastfeeding women and their developing children, may be at higher risk than other populations.METHODS:The authors independently searched the literature for clinical reports or reviews of the literature regarding the safety of cannabis use in pregnancy and breastfeeding using search terms such as cannabis, marijuana, pregnancy and breastfeeding.RESULTS:This review combines the relevant pharmacological, pharmacokinetic and clinical evidence for the effects of cannabis in this special patient population. The literature demonstrates that some of the constituents of cannabis can reach children in utero and through breastmilk. Given that Δ⁹-tetrahydrocannabinol can be present in breastmilk as quickly as 1 hour after consumption and last up to 6 days, it may not be possible to use cannabis and avoid infant exposure. There is evidence that this exposure may result in cognitive, social and motor defects. Some of these effects may be long term, lasting years. The pharmacist must be able to educate and screen patients regarding marijuana use in pregnancy and breastfeeding, with the ultimate aim of harm reduction.

For the treatment of neurological disorders, polyphenols in Vaccinium berry species may be an effective addition to standard medicinal products. Polyphenols may reduce oxidative stress and inflammation, processes believed to contribute to disorders such as Parkinson’s disease. We performed an analysis of polyphenol content, biochemical attributes and neurobiological activity of extracts from wild blueberries native to Newfoundland and Labrador. Fruits and leaves of samples contained several polyphenolic compounds, such as anthocyanins, and demonstrated high antioxidant capacity. Cell cultures of microglia, the innate immune cells of the brain, were exposed to glutamate or α-synuclein in order to induce inflammatory responses, which decreased the amount of cells after 24 h. Overall, treatment of cells with fruit or leaf extracts inhibited cell death and decreased morphological criteria associated with inflammation. These results suggest that dietary intake of blueberry fruits and leaves or supplements may be protective against neurodegenerative disorders that include a neuroinflammatory component.

To demonstrate that repeated episodes of binge drinking during the adolescent period can lead to long-term deficits in motor function and memory in adulthood, and increase proteins in the brain involved with inflammation and apoptotic cell death. Groups of early adolescent (PND 26) and periadolescent (PND 34) Sprague-Dawley rats were exposed to either ethanol or plain air through a vapor chamber apparatus for five consecutive days (2 h per day), achieving a blood ethanol concentration equivalent to 6–8 drinks in the treatment group. Subjects then underwent a series of behavioral tests designed to assess memory, anxiety regulation, and motor function. Brains were collected on PND 94 for subsequent western blot analysis. Behavioral testing using the rota-rod, cage-hang, novel object recognition, light-dark box, and elevated plus maze apparatuses showed significant differences between groups; several of which persisted for up to 60 days after treatment. Western blot testing indicated elevated levels of caspase-3/cleaved caspase-3, NF-kB, and PKC/pPKC proteins in the cerebella of ethanol-treated animals. Differences on anxiety tests indicate a possible failure of behavioral inhibition in the treatment group leading to riskier behavior. Binge drinking also impairs motor coordination and object memory, which involve the cerebellar and hippocampal brain regions, respectively. These experiments indicate the potential dangers of binge drinking while the brain is still developing and indicate the need for future studies in this area.

Several species of berries, such as blueberries (Vaccinium angustifolium) and lingonberries (Vaccinium vitis-idaea L.), have attracted much scientific attention in recent years, especially due to their reported antioxidant and anti-inflammatory properties. Berries, as with other types of plants, have developed metabolic mechanisms to survive various environmental stresses, some of which involve reactive oxygen species. In addition, the fruits and leaves of berries have high amounts of polyphenols, such as flavonoids, which act as potent antioxidants. These compounds could potentially be beneficial for brain aging and neurodegenerative disorders. There are now several studies documenting the beneficial effects of various berries in cell models of neurotoxicity as well as in vivo models of neurodegenerative disease. In the current review, we discuss the metabolic strategies that plants and animals have developed in order to combat reactive oxygen species. We then discuss issues of bioavailability of various compounds in mammals and provide a synopsis of studies demonstrating the neuroprotective ability of berries and polyphenols. We also summarize findings from our own research group. For example, we have detected various polyphenols in samples of blueberries and lingonberries and have found that the leaves have a much higher antioxidant capacity than the fruits. Extracts from these species have also demonstrated neuroprotective effects in cellular models of toxicity and inflammation, which are being further pursued in animal models.

Various species of berries have been reported to contain several polyphenolic compounds, such as anthocyanins and flavonols, which are known to possess high antioxidant activity and may be beneficial for human health. To our knowledge, a thorough chemical analysis of polyphenolics in species of these plants native to Newfoundland, Canada has not been conducted. The primary objective of this study was to determine the polyphenolic compounds present in commercial extracts from Newfoundland berries, which included blueberries (V. angustifolium), lingonberries (V. vitis-idaea) and black currant (Ribes lacustre). Anthocyanin and flavonol glycosides in powdered extracts from Ribes lacustre and the Vaccinium species were identified using the high performance liquid chromatographic (HPLC) separation method with mass spectrometric (MS) detection. The identified compounds were extracted from dried berries by various solvents via ultrasonication followed by centrifugation. A reverse-phase analytical column was employed to identify the retention time of each chemical component before submission for LC–MS analysis. A total of 21 phenolic compounds were tentatively identified in the three species. Further, we tested the effects of the lingonberry extract for its ability to protect neurons and glia from trauma utilizing an in vitro model of cell injury. Surprisingly, these extracts provided complete protection from cell death in this model. These findings indicate the presence of a wide variety of anthocyanins and flavonols in berries that grow natively in Newfoundland. These powdered extracts maintain these compounds intact despite being processed from berry fruit, indicating their potential use as dietary supplements. In addition, these recent findings and previous data from our lab demonstrate the ability of compounds in berries to protect the nervous system from traumatic insults.

The waddles (wdl) mouse is characterized by a namesake "side-to-side" waddling gait due to a homozygous mutation of the Car8 gene. This mutation results in non-functional copies of the protein carbonic anhydrase type 8. Rota-rod testing was conducted to characterize the wdl mutations' effect on motor output. Results indicated that younger homozygotes outperformed their older cohorts, an effect not seen in previous studies. Heterozygotes, which were thought to be free of motor impairment, displayed motor learning deficiencies when compared with wild type performance. Acute cerebellar slices were then utilized for fluorescent calcium imaging experiments, which revealed significant alterations in cerebellar granule cell somatic calcium signaling when exposed to glutamate. The contribution of GABAergic signaling to these alterations was also verified using bath application of bicuculline. Changes in somatic calcium signals were found to be applicable to an in vivo scenario by comparing group responses to electrical stimulation of afferent mossy fiber projections. Finally, intracellular calcium store function was also found to be altered by the wdl mutation when slices were treated with thapsigargin. These findings, taken together with previous work on the wdl mouse, indicate a widespread disruption in cerebellar circuitry hampering proper neuronal communication.

Berry fruits are known for their high antioxidant potential pertaining to their high phenolic content. Antioxidant capacities and phenolic content of blueberry and lingonberry fruits and leaves were studied. Concentrations of total flavonoids, tannins, proanthocyanidin as well as reduced and oxidized levels of ascorbate and glutathione were also determined in these extracts. This study also determined the potential neuroprotective effect of extracts from fruits and leaves against glutamate-mediated excitotoxicity, which is believed to contribute to disorders such as stroke and neurodegenerative diseases. Brain-derived cell cultures from rats were prepared and grown for about 2 weeks. Cell cultures were treated with glutamate (0.1 mM) for 24 h, and the effect of extracts was determined on cells subjected to this excitotoxicity. Blueberry fruits and leaves from both the extracts showed a significant neuroprotective effect. In this study we have shown how phenolic compounds as well as reduced and oxidized levels of ascorbate and glutathione correlate with neuroprotective effect.

Plant-derived polyphenols have attracted the attention of scientists, the public, and the media due to their potential use as nutraceutical products. The high quantities of polyphenols found in some berry species, e.g. Vaccinium species such as blueberries and lingonberries, and their reported antioxidant and anti-inflammatory properties, could be beneficial for brain aging and neurodegenerative disorders. The neuroprotective potential of various polyphenolic compounds have been validated using a variety of in vivo and in vitro techniques. Both in vivo and in vitro methodologies have their respective advantages and disadvantages, including, but not limited to, cost, time, use of resources and technical limitations. For example, in vivo studies can better evaluate the effects of protective compounds and/or their metabolites on various tissues, including the brain, whereas in vitro studies can better discern the cellular and/or mechanistic effects of compounds. This short review is meant to provide a synopsis of some of the inherent benefits and drawbacks of methods used for assessing neuroprotection and how findings may translate to the human population, particularly related to my specific area of research analyzing the potential neuroprotective effects of berries and their associated polyphenolic compounds.

The number of putative neuroprotective compounds with antioxidant activity described in the literature continues to grow. Although these compounds are validated using a variety of in vivo and in vitro techniques, they are often evaluated initially using in vitro cell culture techniques in order to establish toxicity and effective concentrations. Both in vivo and in vitro methodologies have their respective advantages and disadvantages, including, but not limited to, cost, time, use of resources and technical limitations. This review expands on the inherent benefits and drawbacks of in vitro and in vivo methods for assessing neuroprotection, especially in light of proper evaluation of compound efficacy and neural bioavailability. For example, in vivo studies can better evaluate the effects of protective compounds and/or its metabolites on various tissues, including the brain, in the whole animal, whereas in vitro studies can better discern the cellular and/or mechanistic effects of compounds. In particular, we aim to address the question of appropriate and accurate extrapolation of findings from in vitro experiment-where compounds are often directly applied to cellular extracts, potentially at higher concentrations than would ever cross the blood-brain barrier-to the more complex scenario of neuroprotection due to pharmacodynamics in vivo.

Phenolic compounds are a large class of phytochemicals that are widespread in the plant kingdom and known to have antioxidant capacities. This study aimed to determine the antioxidant capacities as well as the content of total soluble phenolics, anthocyanins, tannins, and flavonoids in the fruits and leaves of blueberries and lingonberries growing in Newfoundland. This study also determined the potential neuroprotective effect of extracts from fruits and leaves against glutamate-mediated excitotoxicity, which is believed to contribute to disorders such as stroke and neurodegenerative diseases. Lingonberry and blueberry plants were found to be rich sources of phenolic compounds. Total antioxidant capacities in terms of radical scavenging activity and reducing power were much higher in leaves of both plants as compared to their fruits. These results were in correlation with phenolic contents including total flavonoids, anthocyanins, and tannins. Brain-derived cell cultures from rats were prepared and grown for about 2 weeks. Cell cultures were treated with glutamate (100 μM) for 24 h, and the effect of extracts was determined on cells subjected to this excitotoxicity. Glutamate treatment caused approximately 23% cell loss when measured after 24 h of exposure. Whereas lingonberry fruit extract did not provide protection from glutamate toxicity, blueberry fruit extracts were extremely protective. Leaf extracts of both lingonberry and blueberry showed a significant neuroprotective effect. The greater protective effect of leaf extracts was in correlation with the levels of phenolics and antioxidant capacity. These findings suggest that berries or their components may contribute to protecting the brain from various pathologies.

Ethanol has well described acute effects on motor function, and chronic alcoholism can damage the cerebellum, which is associated with motor coordination, as well as motor learning. Binge drinking is common among preadolescents and adolescents, and this type of ethanol exposure may lead to long-term nervous system damage. In the current study, we analyzed the effects of periadolsecent/adolescent ethanol exposure on motor function in both male and female Sprague-Dawley rats. To simulate binge drinking, animals received an intraperitoneal injection of 25% (v/v) ethanol (3 g/kg) on postnatal days (PND) 25, 26, 29, 30, 33, 34, 37 and 38. On PND 42 and PND 61 animals were tested on their ability to traverse both square and round beams. There were no significant differences in the time to traverse the beams, or the amount of foot slips, between treated and untreated animals. On PND 48 and PND 62, animals were tested using a horizontal ladder walking apparatus. On PND 48 there were no differences in the ability of treated and untreated animals to traverse the ladder. On PND 62, there were no differences in the time to traverse the ladder, but ethanol treated animals had more foot slips than controls. On PND 43, we conducted footprint analysis of control and treated animals, which included measurements of stride length, paw overlap, and angle of foot placement. There was a significant difference in the angle of foot placement between treated and control animals, and this finding was significant for both male and female animals. There was also a significant overall difference in paw overlap between treatment groups. Although this effect was manifested in male animals there was no significant difference in females. These findings suggest that adolescent ethanol exposure can produce long-lasting effects on motor coordination, and that overall, effects are similar in males and females. In a second set of experiments, male rats received i.p. ethanol (3 g/kg) for 7 days (P31-37) or 4 days (P31,33,35,37). No significant differences were detected by footprint analysis when compared to control animals. However, ethanol treated animals had significantly less cerebellar Purkinje cells at 3 weeks after the last ethanol exposure. Altered motor function suggests a possible neurodegenerative effect in the cerebellum initiated by adolescent ethanol exposure, and may depend on the extent of exposure during the preadolescent and/or adolescent brain periods.

Cell death and dysfunction after traumatic brain injury (TBI) is caused by a primary phase, related to direct mechanical disruption of the brain, and a secondary phase which consists of delayed events initiated at the time of the physical insult. Arguably, the calcium ion contributes greatly to the delayed cell damage and death after TBI. A large, sustained influx of calcium into cells can initiate cell death signaling cascades, through activation of several degradative enzymes, such as proteases and endonucleases. However, a sustained level of intracellular free calcium is not necessarily lethal, but the specific route of calcium entry may couple calcium directly to cell death pathways. Other sources of calcium, such as intracellular calcium stores, can also contribute to cell damage. In addition, calcium-mediated signal transduction pathways in neurons may be perturbed following injury. These latter types of alterations may contribute to abnormal physiology in neurons that do not necessarily die after a traumatic episode. This review provides an overview of experimental evidence that has led to our current understanding of the role of calcium signaling in death and dysfunction following TBI.

Oxyresveratrol is a potent antioxidant and free-radical scavenger found in mulberry wood (Morus alba L.) with demonstrated protective effects against cerebral ischemia. We analyzed the neuroprotective ability of oxyresveratrol using an in vitro model of stretch-induced trauma in co-cultures of neurons and glia, or by exposing cultures to high levels of glutamate. Cultures were treated with 25μM, 50μM or 100μM oxyresveratrol at the time of injury. Trauma produced marked neuronal death when measured 24h post-injury, and oxyresveratrol significantly inhibited this death. Microscopic examination of glia suggested signs of toxicity in cultures treated with 100μM oxyresveratrol, as demonstrated by elevated S-100B protein release and a high proportion of cells with condensed nuclei. Cultures exposed to glutamate (100μM) for 24h exhibited ~37% neuronal loss, which was not inhibited by oxyresveratrol. These results show that the two pathologies of high glutamate exposure and trauma are differentially affected by oxyresveratrol treatment in vitro. Further studies using oxyresveratrol in trauma models are warranted, as toxicity to glia could be beneficial by inhibiting reactive gliosis, which often occurs after trauma.

The cerebellum is important for motor coordination, as well as motor learning and memories. Learning is believed to occur in the cerebellar cortex, in the form of synaptic plasticity. Central to motor learning theory are Purkinje cells (PCs), which are the sole output neurons of the cerebellar cortex. Motor memories are postulated to be stored in the form of long-term depression (LTD) at parallel fiber synapses with PCs, once thought to be the only plastic synapse in the cerebellar cortex. However, in the past few decades many studies have demonstrated that several other synapses in the cerebellar cortex are indeed plastic, and that LTD or long-term potentiation at these various synapses could affect the overall output signal of PCs from the cerebellar cortex. Almost all of these forms of synaptic plasticity are dependent on calcium to some extent. In the current review we discuss various types of synaptic plasticity in the cerebellar cortex and the role of calcium in these forms of plasticity.

Dementia in humans following traumatic brain injury (TBI) has been well documented in clinical populations, either after a single TBI or repeated mild TBI (rMTBI). In most cases, trauma-induced dementia follows a slow, chronic time-course, and in many cases mild injuries accumulate over time. Both single TBI and rMTBI have been modeled experimentally in vivo, most often in rodents, and various treatment strategies have been studied in order to reduce brain damage after injury. Here, we review the recent literature with regard to currently used in vivo models of TBI in animals, and studies conducted with them to investigate the link between TBI and the development of dementia-like pathology, such as that associated with Alzheimer’s disease (AD). We also discuss the potential use of in vitro models of trauma for investigating a link between trauma and dementia.

Chronic alcoholism can cause damage to the cerebellum, an area of the brain associated with motor learning and coordination. Recently, we found that adolescent exposure to ethanol in rats can cause altered motor function in adulthood. In the current study, we investigated the effects of adolescent ethanol exposure on the viability of cerebellar Purkinje cells (PCs). To simulate binge drinking, male Sprague‐Dawley rats received an intraperitoneal (i.p.) injection of 25% (v/v) ethanol in isotonic saline (3g/kg) for either 7 days (P31‐37) or 4 days (P31,33,35,37). Controls received an i.p. injection of isotonic saline (P31‐37). Animals administered ethanol displayed obvious loss of motor coordination within minutes of injection. Blood alcohol concentration at 30 min was 275± 16 mg/dl, which represents approximately 12‐15 drink equivalents. On P58, rats were sacrificed and coronal slices of the cerebellum were prepared and stained with cresyl violet. Slices from control animals displayed an intact PC layer. However, rats that had received either 4 or 7 injections of ethanol had a significant loss of PCs as compared to controls. Given the importance of PCs in motor control, these findings suggest that PC death caused by adolescent ethanol exposure may lead to long‐lasting adverse effects on motor coordination. Supported by ABMRF/The Foundation for Alcohol Research and Canada Foundation for Innovation.