Toxicity risk from hip implant CoCrMo particles: The impact of dynamic flow rate on neuronal cells in microfluidic systems.

In patients with total hip replacements (THRs), wear products in the form of nanoparticles and ions are released, especially around implant failure. In this study, we use N2a cells, a neuroblastoma cell line, to evaluate the effects of different flow rates on neuronal toxicity amidst exposure to CoCrMo particles. We hypothesized that increasing flow rates would increase N2a cell viability and decrease N2a cell-degradation products (DPs) toxicity.

A call to implement preclinical study registration in animal ethics review.

Protocol registration is required in clinical trials. Registration of animal studies could improve research transparency and reduce redundancy, yet uptake has been minimal. Integrating study registration into institutional approval of animal use protocols is a promising approach to increase uptake.

Enriched Rehabilitation Reduces Abnormal Motor Synergies and Enhances Motor Plasticity Following Severe Stroke in Rats.

Background: Stroke results in loss of upper motor neuron control over voluntary movements and emergence of abnormal synergies. Presently, it is unclear to what extent poststroke recovery reflects true recovery (restitution), compensation, or some combination of these processes. Here, we investigated this question using behavioral and kinematic analyses of skilled reaching in rats subjected to severe stroke that affected both the forelimb motor cortex and dorsolateral striatum.

Self-reported sleep disturbances among people who have had a stroke: a cross-sectional analysis.

Background: Sleep disturbances and their potential association with stroke remains understudied at a population level. We sought to determine the prevalence of sleep disturbances among people who have effects of stroke compared with the general population.

Methods: We used data from people aged 18 years or older who responded to the sleep and chronic disease modules of the 2017-2018 cycle of the Canadian Community Health Survey (CCHS).

Identifying barriers and enablers to rigorous conduct and reporting of preclinical laboratory studies.

Use of rigorous study design methods and transparent reporting in publications are 2 key strategies proposed to improve the reproducibility of preclinical research. Despite promotion of these practices by funders and journals, assessments suggest uptake is low in preclinical research. Thirty preclinical scientists were interviewed to better understand barriers and enablers to rigorous design and reporting.

Regulation of autoreactive CD4 T cells by FoxO1 signaling in CNS autoimmunity.

Myelin-specific CD4 T effector cells (Teffs), Th1 and Th17 cells, are encephalitogenic in experimental autoimmune encephalomyelitis (EAE), a well-defined murine model of multiple sclerosis (MS) and implicated in MS pathogenesis. Forkhead box O 1 (FoxO1) is a conserved effector molecule in PI3K/Akt signaling and critical in the differentiation of CD4 T cells into T helper subsets. However, it is unclear whether FoxO1 may be a target for redirecting CD4 T cell differentiation and benefit CNS autoimmunity.

Localizing Microemboli within the Rodent Brain through Block-Face Imaging and Atlas Registration.

Brain microinfarcts are prevalent in humans, however because of the inherent difficulty of identifying and localizing individual microinfarcts, brain-wide quantification is impractical. In mice, microinfarcts have been created by surgically introducing microemboli into the brain, but a major limitation of this model is the absence of automated methods to identify and localize individual occlusions. We present a novel and semi-automated workflow to identify the anatomic location of fluorescent emboli (microspheres) within the mouse brain through histologic processing and atlas registration.

Developmental and Interventional Plasticity of Motor Maps after Perinatal Stroke.

Within the perinatal stroke field, there is a need to establish preclinical models where putative biomarkers for motor function can be examined. In a mouse model of perinatal stroke, we evaluated motor map size and movement latency following optogenetic cortical stimulation against three factors of post-stroke biomarker utility: (1) correlation to chronic impairment on a behavioral test battery; (2) amenability to change using a skilled motor training paradigm; and (3) ability to distinguish individuals with potential to respond well to training. mice received a photothrombotic stroke at postnatal day 7 and were evaluated on a battery of motor tests between days 59 and 70.

Remote Ischemic Conditioning and Stroke Recovery.

Remote ischemic conditioning (RIC) is a noninvasive procedure whereby several periods of ischemia are induced in a limb. Although there is growing interest in using RIC to improve stroke recovery, preclinical RIC research has focused exclusively on neuroprotection, using male animals and the intraluminal suture stroke model, and delivered RIC at times not relevant to either brain repair or behavioral recovery. In alignment with the Stroke Recovery and Rehabilitation Roundtable, we address these shortcomings.

An Exercise Mimetic Approach to Reduce Poststroke Deconditioning and Enhance Stroke Recovery.

Evidence supports early rehabilitation after stroke to limit disability. However, stroke survivors are typically sedentary and experience significant cardiovascular and muscular deconditioning. Despite growing consensus that preclinical and clinical stroke recovery research should be aligned, there have been few attempts to incorporate cardiovascular and skeletal muscle deconditioning into animal models of stroke.

Neuroprotection by Remote Ischemic Conditioning in Rodent Models of Focal Ischemia: a Systematic Review and Meta-Analysis.

Remote ischemic conditioning (RIC) is a promising neuroprotective therapy for ischemic stroke. Preclinical studies investigating RIC have shown RIC reduced infarct volume, but clinical trials have been equivocal. Therefore, the efficacy of RIC in reducing infarct volume and quality of current literature needs to be evaluated to identify knowledge gaps to support future clinical trials.

The Home-Cage Automated Skilled Reaching Apparatus (HASRA): Individualized Training of Group-Housed Mice in a Single Pellet Reaching Task.

The single pellet reaching task is commonly used in rodents to assess the acquisition of fine motor skill and recovery of function following nervous system injury. Although this task is useful for gauging skilled forelimb use in rodents, the process of training animals is labor intensive and variable across studies and labs. To address these limitations, we developed a single pellet reaching paradigm for training and testing group housed mice within their home cage.

Poststroke Impairment and Recovery Are Predicted by Task-Specific Regionalization of Injury.

Lesion size and location affect the magnitude of impairment and recovery following stroke, but the precise relationship between these variables and functional outcome is unknown. Herein, we systematically varied the size of strokes in motor cortex and surrounding regions to assess effects on impairment and recovery of function. Female Sprague Dawley rats ( = 64) were evaluated for skilled reaching, spontaneous limb use, and limb placement over a 7 week period after stroke.

Influence of metabolic syndrome on cerebral perfusion and cognition.

Vascular cognitive impairment (VCI) is associated with chronic cerebral hypoperfusion (CCH) and memory deficits, and often occurs concurrently with metabolic syndrome (MetS). Despite their common occurrence, it is unknown whether CCH and MetS act synergistically to exacerbate VCI-associated pathology. Here, using male Sprague-Dawley rats, we examined the effects of a clinically relevant model of adolescent-onset MetS and adult-onset CCH on neuro-vascular outcomes, combining a cafeteria diet with a 2-vessel occlusion (2VO) model.

Cognition in Stroke Rehabilitation and Recovery Research: Consensus-Based Core Recommendations From the Second Stroke Recovery and Rehabilitation Roundtable.

Cognitive impairment is an important target for rehabilitation as it is common following stroke, is associated with reduced quality of life and interferes with motor and other types of recovery interventions. Cognitive function following stroke was identified as an important, but relatively neglected area during the first Stroke Recovery and Rehabilitation Roundtable (SRRR I), leading to a Cognition Working Group being convened as part of SRRR II. There is currently insufficient evidence to build consensus on specific approaches to cognitive rehabilitation.

Cognition in stroke rehabilitation and recovery research: Consensus-based core recommendations from the second Stroke Recovery and Rehabilitation Roundtable.

Cognitive impairment is an important target for rehabilitation as it is common following stroke, is associated with reduced quality of life and interferes with motor and other types of recovery interventions. Cognitive function following stroke was identified as an important, but relatively neglected area during the first Stroke Recovery and Rehabilitation Roundtable (SRRR I), leading to a Cognition Working Group being convened as part of SRRR II. There is currently insufficient evidence to build consensus on specific approaches to cognitive rehabilitation.

An RFID-based activity tracking system to monitor individual rodent behavior in environmental enrichment: Implications for post-stroke cognitive recovery.

Background: Diminished cognitive flexibility is a common form of executive dysfunction that results from stroke in the prefrontal cortex. Potential therapies targeting this type of cognitive deficit following stroke are lacking.

New Method: Here, we used environmental enrichment (EE) as a rehabilitation approach, integrated with a radio frequency identification (RFID)-based activity tracking system to evaluate the contribution of individual EE elements to promote cognitive recovery.

Characterizing Spontaneous Motor Recovery Following Cortical and Subcortical Stroke in the Rat.

Background: Stroke is a leading cause of neurological disability, often resulting in long-term motor impairments due to damage to cortical or subcortical motor areas. Despite the high prevalence of subcortical strokes in the clinical population, preclinical research has primarily focused on investigating and treating cortical strokes. Moreover, while both humans and animals show spontaneous recovery following stroke, little is known about how injury location affects this process.

Electromagnetic simulation for diagnosing damage to femoral neck vasculature: A feasibility study.

Background: Femoral neck fractures are common injuries managed by orthopedic surgeons across the world. From pediatrics to geriatrics, disruption of the blood supply to the femoral neck is a well-recognized source of morbidity and mortality, oftentimes resulting in avascular necrosis of the femoral head. This devastating complication occurs in 10-45% of femoral neck fractures.

Is Environmental Enrichment Ready for Clinical Application in Human Post-stroke Rehabilitation?

Environmental enrichment (EE) has been widely used as a means to enhance brain plasticity mechanisms (e.g., increased dendritic branching, synaptogenesis, etc.

Metformin Preconditioning of Human Induced Pluripotent Stem Cell-Derived Neural Stem Cells Promotes Their Engraftment and Improves Post-Stroke Regeneration and Recovery.

While transplantation of human induced pluripotent stem cell-derived neural stem cells (hiPSC-NSCs) shows therapeutic potential in animal stroke models, major concerns for translating hiPSC therapy to the clinic are efficacy and safety. Therefore, there is a demand to develop an optimal strategy to enhance the engraftment and regenerative capacity of transplanted hiPSC-NSCs to produce fully differentiated neural cells to replace lost brain tissues. Metformin, an FDA-approved drug, is an optimal neuroregenerative agent that not only promotes NSC proliferation but also drives NSCs toward differentiation.

Post-stroke kinematic analysis in rats reveals similar reaching abnormalities as humans.

A coordinated pattern of multi-muscle activation is essential to produce efficient reaching trajectories. Disruption of these coordinated activation patterns, termed synergies, is evident following stroke and results in reaching deficits; however, preclinical investigation of this phenomenon has been largely ignored. Furthermore, traditional outcome measures of post-stroke performance seldom distinguish between impairment restitution and compensatory movement strategies.