Evaluation of the Parkinson's Remote Interactive Monitoring System in a Clinical Setting: Usability Study.

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.

The Pathology of Parkinson's Disease and Potential Benefit of Dietary Polyphenols.

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.

Cannabis use in pregnancy and breastfeeding: The pharmacist's role.

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 and .

Binge drinking in male adolescent rats and its relationship to persistent behavioral impairments and elevated proinflammatory/proapoptotic proteins in the cerebellum.

Rationale: 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.

Methods: 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.

Biochemical Properties and Neuroprotective Effects of Compounds in Various Species of Berries.

Several species of berries, such as blueberries () and lingonberries ( 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.

Chemical Analysis of Extracts from Newfoundland Berries and Potential Neuroprotective Effects.

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 (), lingonberries () and black currant ().

Mice deficient in carbonic anhydrase type 8 exhibit motor dysfunctions and abnormal calcium dynamics in the somatic region of cerebellar granule cells.

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.

Assessing Antioxidant Capacity in Brain Tissue: Methodologies and Limitations in Neuroprotective Strategies.

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.

Chemical analysis and effect of blueberry and lingonberry fruits and leaves against glutamate-mediated excitotoxicity.

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.

Effects of intermittent binge alcohol exposure on long-term motor function in young rats.

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.

Altered calcium signaling following traumatic brain injury.

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.

Potential neuroprotective effects of oxyresveratrol against traumatic injury.

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.

The role of calcium in synaptic plasticity and motor learning in the cerebellar cortex.

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.

Causal role of apoptosis-inducing factor for neuronal cell death following traumatic brain injury.

Traumatic brain injury (TBI) consists of two phases: an immediate phase in which damage is caused as a direct result of the mechanical impact; and a late phase of altered biochemical events that results in delayed tissue damage and is therefore amenable to therapeutic treatment. Because the molecular mechanisms of delayed post-traumatic neuronal cell death are still poorly understood, we investigated whether apoptosis-inducing factor (AIF), a pro-apoptotic mitochondrial molecule and the key factor in the caspase-independent, cell death signaling pathway, plays a causal role in neuronal death following TBI. Using an in vitro model of neuronal stretch injury, we demonstrated that AIF translocated from mitochondria to the nucleus of neurons displaying axonal disruption, chromatin condensation, and nuclear pyknosis in a caspase-independent manner, whereas astrocytes remained unaffected.

Alcohol impairs long-term depression at the cerebellar parallel fiber-Purkinje cell synapse.

Acute alcohol consumption causes deficits in motor coordination and gait, suggesting an involvement of cerebellar circuits, which play a role in the fine adjustment of movements and in motor learning. It has previously been shown that ethanol modulates inhibitory transmission in the cerebellum and affects synaptic transmission and plasticity at excitatory climbing fiber (CF) to Purkinje cell synapses. However, it has not been examined thus far how acute ethanol application affects long-term depression (LTD) and long-term potentiation (LTP) at excitatory parallel fiber (PF) to Purkinje cell synapses, which are assumed to mediate forms of cerebellar motor learning.

Changes of cerebral blood flow during the secondary expansion of a cortical contusion assessed by 14C-iodoantipyrine autoradiography in mice using a non-invasive protocol.

Although changes of cerebral blood flow (CBF) in and around traumatic contusions are well documented, the role of CBF for the delayed death of neuronal cells in the traumatic penumbra ultimately resulting in secondary contusion expansion remains unclear. The aim of the current study was therefore to investigate the relationship between changes of CBF and progressive peri-contusional cell death following traumatic brain injury (TBI). CBF and contusion size were measured in C57Bl6 mice under continuous on-line monitoring of (ETp)CO2 before, and at 15 min and 24 h following controlled cortical impact by 14C-iodoantipyrine autoradiography (IAP-AR; n = 5-6 per group) and by Nissl staining, respectively.

Aldolase C-positive cerebellar Purkinje cells are resistant to delayed death after cerebral trauma and AMPA-mediated excitotoxicity.

The cerebellum has been shown to be vulnerable to global ischemic damage in tightly controlled zones of Purkinje cells (PCs) that lack aldolase C, an enzyme critical for glycolysis. Here, we investigated whether aldolase C-negative PCs were more likely to die after cerebral trauma in vivo, and whether this death was mediated by excitotoxic [alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-mediated] means in vitro. Mice were subjected to controlled cortical impact, or remained uninjured, and were killed at 6 h, 24 h or 7 days after injury.

Experimental models of repetitive brain injuries.

Repetitive traumatic brain injury (TBI) occurs in a significant portion of trauma patients, especially in specific populations, such as child abuse victims or athletes involved in contact sports (e.g. boxing, football, hockey, and soccer).

Climbing fiber-triggered metabotropic slow potentials enhance dendritic calcium transients and simple spike firing in cerebellar Purkinje cells.

Cerebellar Purkinje cells (PCs) receive synaptic input from numerous parallel fibers (PFs) and from a single climbing fiber (CF). At both types of synapses, fast synaptic transmission is mediated by AMPA receptors, while at PF synapses burst activity can additionally recruit metabotropic glutamate receptors (mGluRs) that mediate a slow depolarizing potential. Here, we show that mGluR-activated slow potentials can be evoked throughout the dendrite by CF-evoked complex spike firing in the presence of an mGluR agonist.

Calcium homeostasis following traumatic neuronal injury.

Cell death and dysfunction following traumatic brain injury (TBI) consists of a primary phase, which causes immediate consequences to cells by direct mechanical disruption of the brain, and a secondary phase which consists of delayed events initiated at the time of insult. One of the major culprits that contributes to delayed neuronal damage and death after a traumatic insult is the calcium ion. The original calcium hypothesis suggests that a large, sustained influx of calcium into cells initiates cell death signalling cascades.

Combined effects of mechanical and ischemic injury to cortical cells: secondary ischemia increases damage and decreases effects of neuroprotective agents.

Traumatic brain injury (TBI) involves direct mechanical damage, which may be aggravated by secondary insults such as ischemia. We utilized an in vitro model of stretch-induced injury to investigate the effects of mechanical and combined mechanical/ischemic insults to cultured mouse cortical cells. Stretch injury alone caused significant neuronal loss and increased uptake of the dye, propidium iodide, suggesting cellular membrane damage to both glia and neurons.

The extent of damage following repeated injury to cultured hippocampal cells is dependent on the severity of insult and inter-injury interval.

Recent evidence suggests repeated mild brain trauma may result in cumulative damage. We investigated cell damage and death in hippocampal cultures following repeated mechanical trauma in vitro by measuring propidium iodide (PrI) uptake, release of neuron-specific enolase (NSE) and glial S-100beta protein, and performing neuronal counts. Cultures receiving two mild injuries (31% stretch) 1 or 24 h apart displayed different profiles of PrI uptake and S-100beta release, although neuronal loss and NSE release was similar in both paradigms.

Don't get too excited: mechanisms of glutamate-mediated Purkinje cell death.

Purkinje cells (PCs) present a unique cellular profile in both the cerebellum and the brain. Because they represent the only output cell of the cerebellar cortex, they play a vital role in the normal function of the cerebellum. Interestingly, PCs are highly susceptible to a variety of pathological conditions that may involve glutamate-mediated 'excitotoxicity', a term coined to describe an excessive release of glutamate, and a subsequent over-activation of excitatory amino acid (NMDA, AMPA, and kainite) receptors.

Bidirectional parallel fiber plasticity in the cerebellum under climbing fiber control.

Cerebellar parallel fiber (PF)-Purkinje cell (PC) synapses can undergo postsynaptically expressed long-term depression (LTD) or long-term potentiation (LTP) depending on whether or not the climbing fiber (CF) input is coactivated during tetanization. Here, we show that modifications of the postsynaptic calcium load using the calcium chelator BAPTA or photolytic calcium uncaging result in a reversal of the expected polarity of synaptic gain change. At higher concentrations, BAPTA blocks PF-LTP.

Glutamate-induced elevations in intracellular chloride concentration in hippocampal cell cultures derived from EYFP-expressing mice.

The homeostasis of intracellular Cl(-) concentration ([Cl(-)](i)) is critical for neuronal function, including gamma-aminobutyric acid (GABA)ergic synaptic transmission. Here, we investigated activity-dependent changes in [Cl(-)](i) using a transgenetically expressed Cl(-)-sensitive enhanced yellow-fluorescent protein (EYFP) in cultures of mouse hippocampal neurons. Application of glutamate (100 microm for 3 min) in a bath perfusion to cell cultures of various days in vitro (DIV) revealed a decrease in EYFP fluorescence.