Significant Motor Impairment Research Articles

Rest the brain to learn new gait patterns after stroke

BackgroundThe ability to relearn a lost skill is critical to motor recovery after a stroke. Previous studies indicate that stroke typically affects the processes underlying motor control and execution but not the learning of those skills. However, these studies could be confounded by the presence of significant motor impairments. Furthermore, prior research involving the upper extremity indicates that stroke survivors have an advantage in offline motor learning when compared with controls. However, this has not been examined using motor acuity tasks (i.e., tasks focusing on the quality of executed actions) that have direct functional relevance to rehabilitation.ObjectiveInvestigate how stroke affects leg motor skill learning during walking in stroke survivors.MethodsTwenty-five participants (10 stroke; 15 controls) were recruited for this prospective, case-control study. Participants learned a novel foot-trajectory tracking task on two consecutive days while walking on a treadmill. The task necessitated greater hip and knee flexion during the swing phase of the gait. Online learning was measured by comparing tracking error at the beginning and end of each practice session, offline (rest-driven) learning was measured by comparing the end of the first practice session to the beginning of the second, and retention was measured by comparing the beginning of the first practice session to the beginning of the second. Online learning, offline learning, and retention were compared between the stroke survivors and uninjured controls.ResultsStroke survivors improved their tracking performance on the first day (p = 0.033); however, the amount of learning in stroke survivors was lower in comparison with the control group on both days (p ≤ 0.05). Interestingly, stroke survivors showed higher offline learning gains when compared with uninjured controls (p = 0.011).ConclusionsEven stroke survivors with no perceivable motor impairments have difficulty acquiring new motor skills related to walking, which may be related to the underlying neural damage caused at the time of stroke. Furthermore, stroke survivors may require longer training with adequate rest to acquire new motor skills.

Cerebellar haemorrhage and atrophy in infants born extremely preterm with intraventricular haemorrhage.

To investigate the impact of cerebellar haemorrhage (CBH) and atrophy in infants born extremely preterm with intraventricular haemorrhage (IVH) on neurodevelopment at 2 years of age. This retrospective case-control study included infants born at less than 28 weeks' gestation with IVH over a 10-year period. CBH, along with the assessment of cerebellar size, using magnetic resonance imaging, were studied. The impact of injuries on neurodevelopmental outcome at 2 years' corrected age was conducted, using multivariable regression analysis for comprehensive evaluation. In a cohort of 103 patients, 69 (67.0%) showed CBH with a median grade of 1 (interquartile range = 0-3). At the corrected age of 2 years, CBH was significantly associated with impaired cognitive and motor outcome. CBH emerged as an independent predictor of poor cognitive and motor development, as well as cerebral palsy. Cerebellar atrophy, affecting 30 (29.1%) infants, was linked to a significantly worse outcome across all domains. Conversely, an increase in cerebellar size was correlated with improved motor development. Infants born extremely preterm with IVH and concomitant CBH exhibited significant cognitive and motor impairment. The severity of developmental delay correlated with the grade of CBH. These findings hold potential to support the prediction of long-term outcome and parental counselling.

Deletion of Slc1a4 Suppresses Single Mauthner Cell Axon Regeneration In Vivo through Growth-Associated Protein 43.

Spinal cord injury (SCI) is a debilitating central nervous system (CNS) disorder that leads to significant motor and sensory impairments. Given the limited regenerative capacity of adult mammalian neurons, this study presents an innovative strategy to enhance axonal regeneration and functional recovery by identifying a novel factor that markedly promotes axonal regeneration. Employing a zebrafish model with targeted single axon injury in Mauthner cells (M-cells) and utilizing the Tg (Tol056: EGFP) transgenic line for in vivo monitoring, we investigate the intrinsic mechanisms underlying axonal regeneration. This research specifically examines the role of amino acid transport, emphasizing the role of the solute carrier 1A4 amino acid transporter in axonal regeneration. Our findings demonstrate that Slc1a4 overexpression significantly enhances axonal regeneration in M-cells, whereas Slc1a4 deficiency impedes this process, which is concomitant with the downregulation of the P53/Gap43 signaling pathway. By elucidating the fundamental role of Slc1a4 in axonal regeneration and uncovering its underlying mechanisms, this study thus provides novel insights into therapeutic strategies for SCI.

Biomimetic multi-channel nerve conduits with micro/nanostructures for rapid nerve repair

Peripheral nervous system (PNS) injuries often lead to significant sensory and motor impairments. Traditional artificial nerve conduits, lacking anisotropic structures, have been associated with prolonged repair time and failures in nerve regeneration. This study aimed to address these challenges by developing a novel approach for rapid repair of peripheral nerve injuries (PNI). A 3D oriented fibers scaffold featuring distinct radial (RFs) and longitudinal (LFs) fibers orientations was engineered using coaxial electrospinning and gas directional foaming techniques. This scaffold was then integrated with a shape memory conduit to form a directional multi-channel nerve conduit with micro/nanostructures. The results revealed that the grooved surface of the fibers significantly improved cellular directional guidance, effectively facilitating the migration of SCs from the periphery towards the center and from the base to the apex of the scaffold. In a rat model with a 10 mm nerve defect, the ND-PLATMC/LF ND-PCL scaffold significantly enhanced nerve regeneration and motor function recovery within 4 weeks. These results suggest the potential of this innovative scaffold for efficient repair of the nerve injuries.

Heterozygous loss of Engrailed-1 and α-synucleinopathy (En1/SYN): A dual-hit preclinical mouse model of Parkinson's disease, analyzed with artificial intelligence

In this study, we develop and validate a new Parkinson's disease (PD) mouse model that can be used to better understand how the disease progresses and to test the effects of new, potentially disease-modifying, PD therapies. Our central hypothesis is that mitochondrial dysfunction intercalates with misfolded α-synuclein (α-syn) accumulation in a vicious cycle, leading to the loss of nigral neurons. Our hypothesis builds on the concept that PD involves multiple molecular insults, including mitochondrial dysfunction and aberrant α-syn handling. We predicted that mitochondrial deficits, due to heterozygous loss of Engrailed-1 (En1+/−), combined with bilateral injections of pathogenic α-syn fibrils (PFFs), will act to generate a highly relevant PD model – the En1/SYN model. Here, En1+/− mice received bilateral intrastriatal stereotaxic injections of either PBS or α-syn fibrils and were analyzed using automated behavioral tests and deep learning-assisted histological analysis at 2, 4, and 6 months post-injection. We observed significant and progressive Lewy body-like inclusion pathology in the amygdala, motor cortex, and cingulate cortex, as well as the loss of tyrosine hydroxylase-positive (TH+) cells in the substantia nigra. The En1/SYN model also exhibited significant motor impairments at 6 months post-injection, which were however not exacerbated as we had expected. Still, this model has a comprehensive number of PD-like phenotypes and is therefore superior when compared to the α-syn PFF or En1+/− models alone.

Targeted therapy and deep learning insights into microglia modulation for spinal cord injury

Spinal cord injury (SCI) is a devastating condition that can cause significant motor and sensory impairment. Microglia, the central nervous system's immune sentinels, are known to be promising therapeutic targets in both SCI and neurodegenerative diseases. The most effective way to deliver medications and control microglial inflammation is through nanovectors; however, because of the variability in microglial morphology and the lack of standardized techniques, it is still difficult to precisely measure their activation in preclinical models. This problem is especially important in SCI, where the intricacy of the glia response following traumatic events necessitates the use of a sophisticated method to automatically discern between various microglial cell activation states that vary over time and space as the secondary injury progresses. We address this issue by proposing a deep learning-based technique for quantifying microglial activation following drug-loaded nanovector treatment in a preclinical SCI model. Our method uses a convolutional neural network to segment and classify microglia based on morphological characteristics. Our approach's accuracy and efficiency are demonstrated through evaluation on a collection of histology pictures from injured and intact spinal cords. This robust computational technique has potential for analyzing microglial activation across various neuropathologies and demonstrating the usefulness of nanovectors in modifying microglia in SCI and other neurological disorders. It has the ability to speed development in this crucial sector by providing a standardized and objective way to compare therapeutic options.

Abstract TMP120: Contralesional Corticospinal Tract Reinnervates Cervical Spinal Anatomical Regions With Highest Pre-Lesion Synapse Density After Unilateral M1 Stroke in Mice

Introduction: Stroke leaves many patients with significant motor impairment. Following ischemic lesions of the rodent primary motor cortex, sprouting of the contralesional corticospinal tract (cCST) into the injured hemicord is associated with improved motor recovery. In adult mice, most corticospinal neurons project to spinal interneurons, and few synapse directly on alpha motor neurons. We examined the distribution of newly formed corticospinal synapses in the mouse spinal cord, using genetically encoded tracers, 3D microscopy, and a spinal atlas with machine learning-based automated classification and registration. Hypothesis: We tested the hypothesis that cCST neurons innervate homotopic regions in the injured hemicord after unilateral motor cortex stroke in adult mice. Method: We induced a photothrombotic motor cortex stroke or performed sham surgery (n=4 per group) in 8-11 week old male C57/B6 mice and administered a contralesional motor cortex injection of an anterograde adeno-associated virus expressing both membrane-targeted tdTomato and synaptically-targeted eGFP. Cervical spinal cords were subjected to volumetric imaging via serial two-photon tomography (TissueCyte 1000) to characterize synaptic and axonal density of cCST collaterals in whole cervical spinal cords in both stroke and sham mice. Unbiased, global quantification of axonal and synaptic density across the entire cervical cord was accomplished by the development of a custom automated image analysis pipeline, incorporating a novel 3D spinal cord reference volume, published spinal cord annotations comprising 47 distinct anatomical regions (SpinalJ), and machine learning based pixel classification. Results: We observed cCST synapses in the 6-week post-stroke injured hemicord innervating lamina IV & IX most densely at C7 & C8 (See Figure). Conclusions: Contralesional CST reinnervation of the denervated hemicord is targeted to both lamina and cervical level specific.

Patient-advocate-led global coalition adapting fit-for-purpose outcomes measures to assure meaningful inclusion of DEEs in clinical trials.

Existing clinical tools that measure non-seizure outcomes lack the range and granularity needed to capture skills in developmental and epileptic encephalopathy (DEE)-affected individuals who also fall in the severe to profound range of intellectual disability. This effectively excludes those with severe impairments from clinical trials, impeding the ability of sponsors to evaluate disease-modifying therapies (DMTs). The Inchstone Project, an international, patient advocate-led collaboration, brings together leading researchers, clinicians, pharmaceutical companies, and advocates to develop an adapted, validated assessment battery within 5 years. The goal is to support trials of DMTs for the DEEs by providing sufficiently sensitive measurement tools to demonstrate therapeutic efficacy. An initial pilot study administered 7 established assessments to 10 individuals affected by SCN2A-DEE, identifying specific limitations of existing measures and areas for improvement. It was clear that most tools do not account for challenges throughout the DEE population, including vision impairments, significant motor impairments and profound intellectual disability, which need to be accounted for in creating a 'fit-for-purpose' battery for the DEE population. Several novel assessments, including two measures of responsivity developed for use in monitoring recovery after acquired brain injury as well as individualized Goal Attainment Scaling, showed promise in this group. The team also completed a DEE-wide survey with over 270 caregivers documenting their children's abilities and priorities for their improvement from new treatments. The Inchstone team is using this information to evaluate how existing tools might be updated to better capture what is most important to families and measure their child's small but important improvements over time. These efforts are building a coherent picture across multiple DEEs of what domains, or concepts of interest, have the greatest impact on most patients and families. The Inchstone team is on course to adapt non-seizure outcome measures that are (1) sufficiently sensitive to measure small increments of meaningful change ('Inchstones') and (2) applicable to multiple DEE conditions.

Clinical and laboratory status in Parkinson’s disease patients with and without polyneuropathy

Background/Aim. The etiology of polyneuropathy (PNP) in patients with Parkinson?s disease (PD) is unclear, and there is a possible association between levodopa therapy, hyperhomocysteinemia, and PNP development due to methylation processes involving vitamin B12 and folic acid. The aim of this study was to analyze the difference in clinical presentation and disease severity between PD patients with and without PNP and to evaluate blood levels of vita-min B12, homocysteine, and folic acid in these patients. Methods. This cross-sectional study included 200 consecutive patients diagnosed with PD, divided into two groups: those with PNP and those without PNP. Diagnosis of PNP was confirmed by electromyoneurography. The first group consisted of 50 patients with PD with confirmed PNP, and the second 50 patients with PD without PNP. All patients were receiving levodopa therapy. Laboratory tests analyzed vitamin B12, folic acid, and homocysteine levels. Results. Patients with PNP were older when PNP was diagnosed (71 vs. 66 years, p < 0.0001), without differences in duration of levodopa therapy (p = 0.359) or daily dose (p = 0.442), and with significant motor impairment according to Unified Parkinson?s Disease Rating Scale III (p = 0.017). No difference was found between groups for vitamin B12 (p = 1.0), folic acid (p = 0.124), and homocysteine (p = 0.313) serum levels. Conclusion. PD patients with PNP have a more pronounced motor deficit, while differences in vitamin B12, homocysteine, and folic acid values compared to the group without PNP were not registered.

The role of ventral tegmental area in chronic stroke rehabilitation: an exploratory study.

The acknowledged role of external rewards in chronic stroke rehabilitation, offering positive reinforcement and motivation, has significantly contributed to patient engagement and perseverance. However, the exploration of self-reward's importance in this context remains limited. This study aims to investigate the functional connectivity of the ventral tegmental area (VTA), a key node in the brain's reward circuitry, during motor task-based rehabilitation and its correlation with the recovery process. Twelve right-handed healthy volunteers (4 men, 8 women, aged 57.4 ± 11.3 years) and twelve chronic stroke patients (5 men, 7 women, aged 48.1 ± 11.1 years) with clinically significant right-sided motor impairment (mean FM-UE score of 27.6 ± 8.7) participated. The analysis employed the CONN toolbox to assess the association between motor tasks and VTA connectivity using psychophysiological interaction (PPI). PPI analysis revealed motor-dependent changes in VTA connectivity, particularly with regions within the motor circuitry, cerebellum, and prefrontal cortex. Notably, stronger connectivity between the ipsilesional VTA and cerebellum was observed in healthy controls compared to chronic stroke patients, highlighting the importance of VTA-cerebellum interactions in motor function. Stroke patients' motor performance was associated with VTA modulation in areas related to both motor tasks and reward processing, emphasizing the role of self-reward processes in rehabilitation. Changes in VTA influence on motor circuitry were linked to improvements in motor performance resulting from rehabilitation. Our findings underscore the potential of neuroimaging techniques in quantifying and predicting rehabilitation outcomes by examining self-reward processes. The observed associations between VTA connectivity and motor performance in both healthy and stroke-affected individuals emphasize the role of psychological factors, particularly self-reward, in the rehabilitation process. This study contributes valuable insights into the intricate interplay between reward circuits and motor function, highlighting the importance of addressing psychological dimensions in neurorehabilitation strategies.

Epidemiology, causes, and morbidities of stroke in the young.

The purpose is to describe the latest research on epidemiology, causes, and morbidities of stroke in neonates and children. The global incidence of childhood stroke is approximately 2 per 100 000 person-years, which is significantly lower compared to neonates (20-40 per 100 000 live births) and adults (80-90 per 100 000 person-years). Placental abnormalities are a risk factor for perinatal stroke, although cause is usually multifactorial. In children, nonatherosclerotic arteriopathies and arteriovenous malformations are major causes of ischemic and hemorrhagic strokes, respectively. The perinatal period confers a high risk of stroke and can lead to long-term disability, including motor delay, cognitive or speech impairment, and epilepsy. Recent studies suggest that at least 50% of survivors of perinatal stroke have abnormal neurodevelopmental scores in long-term follow up. Childhood stroke is associated with significant morbidity, including epilepsy, motor impairments, and behavioral disability. Recent studies have also identified an association between pediatric stroke and behavioral disorders, such as attention deficit hyperactivity disorder and autism. Perinatal and childhood strokes are important causes of neurological morbidity. Given the low incidence of childhood stroke, prospective research studies on epidemiology, causes, and outcomes remain limited, highlighting the need for continued multisite collaborations.

Chronic carbon disulfide exposure induces parkinsonian pathology via α-synuclein aggregation and necrosome complex interaction

Exposure to carbon disulfide (CS2) has been associated with an increased incidence of parkinsonism in workers, but the mechanism underlying this association remains unclear. Using a rat model, we investigated the effects of chronic CS2 exposure on parkinsonian pathology. Our results showed that CS2 exposure leads to significant motor impairment and neuronal damage, including loss of dopaminergic neurons and degeneration of the substantia nigra pars compacta (SNpc). The immunoassays revealed that exposure to CS2 induces aggregation of α-synuclein and phosphorylated α-synuclein, as well as activation of necroptosis in the SNpc. Furthermore, invitro and invivo experiments demonstrated that the interaction between α-synuclein and the necrosome complex (RIP1, RIP3, and MLKL) is responsible for the loss of neuronal cells after CS2 exposure. Taken together, our results demonstrate that CS2-mediated α-synuclein aggregation can induce dopaminergic neuron damage and parkinsonian behavior through interaction with the necrosome complex.

Tactile stimulation facilitates functional recovery and dendritic change following neonatal hemidecortication in rats

After large neocortical lesions, such as hemidecortication, children can show significant motor and cognitive impairments. It thus is of considerable interest to identify treatments that might enhance long-term functional outcome. We have previously shown that tactile stimulation enhances recovery from perinatal focal cortical lesions in rats, so the goal of the present experiment was to explore the effectiveness of postlesion tactile stimulation in reducing functional deficits associated with neonatal hemidecortication. Rats were given hemidecortications on postnatal day 10 (P10). Half of the group was then exposed to a daily tactile stimulation treatment for 15 min, three times a day for eleven days following the surgery. All groups were then tested on a number of behavioural tasks (Morris water task, skilled reaching, forelimb placing during spontaneous vertical exploration, and a sunflower seed opening task) beginning at P 120. The brains of the male animals were prepared for Golgi-Cox staining and subsequent analysis of dendritic arborisation and spine density. There were two main findings in this experiment: 1) Tactile stimulation improved cognitive ability and some motor performance after P 10 hemidecortication; and, 2) Tactile stimulation altered cortical organization after P10 hemidecortication. Tactile stimulation may provide an important noninvasive therapy after hemispherectomy in children.

F-words and early intervention ingredients for non-ambulant children with cerebral palsy: A scoping review.

To explore the ingredients of early interventions provided to young children with cerebral palsy (CP) who are classified in Gross Motor Function Classification System (GMFCS) levels IV and V, and to identify the 'F-words' addressed by the interventions. Searches were completed in four electronic databases. Inclusion criteria were the original experimental studies that fitted the following PCC components: population, young children (aged 0-5 years, at least 30% of the sample) with CP and significant motor impairment (GMFCS levels IV or V, at least 30% of the sample); concept, non-surgical and non-pharmacological early intervention services measuring outcomes from any of the International Classification of Functioning, Disability and Health domains; and context, studies published from 2001 to 2021, from all settings and not limited to any specific geographical location. Eighty-seven papers were included for review, with qualitative (n = 3), mixed-methods (n = 4), quantitative descriptive (n = 22), quantitative non-randomized (n = 39), and quantitative randomized (n = 19) designs. Fitness (n = 59), family (n = 46), and functioning (n = 33) ingredients were addressed by most experimental studies, whereas studies on fun (n = 6), friends (n = 5), and future (n = 14) were scarce. Several other factors (n = 55) related to the environment, for example, service provision, professional training, therapy dose, and environmental modifications, were also relevant. Many studies positively supported formal parent training and use of assistive technology to promote several F-words. A menu of intervention ingredients was provided, with suggestions for future research, to incorporate them into a real context within the family and clinical practice. Family-centred care (including coaching and caregiver-delivered interventions) and formal parental training are effective strategies for children in GMFCS levels IV and V. Assistive technology ingredients (power, mobility, supported, sitting, stepping, and standing) may promote several 'F-words' (functioning, fitness, family, fun, friends, and future). The lowest level of evidence was found for fun, friends, and future. Other factors (service provision, professional training, therapy dose, environmental modifications) are relevant for young children in GMFCS levels IV and V.

The pathogenesis of DLD-mediated cuproptosis induced spinal cord injury and its regulation on immune microenvironment.

Spinal cord injury (SCI) is a severe central nervous system injury that leads to significant sensory and motor impairment. Copper, an essential trace element in the human body, plays a vital role in various biological functions and is strictly regulated by copper chaperones and transporters. Cuproptosis, a novel type of metal ion-induced cell death, is distinct from iron deprivation. Copper deprivation is closely associated with mitochondrial metabolism and mediated by protein fatty acid acylation. In this study, we investigated the effects of cuproptosis-related genes (CRGs) on disease progression and the immune microenvironment in acute spinal cord injury (ASCI) patients. We obtained the gene expression profiles of peripheral blood leukocytes from ASCI patients using the Gene Expression Omnibus (GEO) database. We performed differential gene analysis, constructed protein-protein interaction networks, conducted weighted gene co-expression network analysis (WGCNA), and built a risk model. Our analysis revealed that dihydrolipoamide dehydrogenase (DLD), a regulator of copper toxicity, was significantly associated with ASCI, and DLD expression was significantly upregulated after ASCI. Furthermore, gene ontology (GO) enrichment analysis and gene set variation analysis (GSVA) showed abnormal activation of metabolism-related processes. Immune infiltration analysis indicated a significant decrease in T cell numbers in ASCI patients, while M2 macrophage numbers were significantly increased and positively correlated with DLD expression. In summary, our study demonstrated that DLD affects the ASCI immune microenvironment by promoting copper toxicity, leading to increased peripheral M2 macrophage polarization and systemic immunosuppression. Thus, DLD has potential as a promising biomarker for ASCI, providing a foundation for future clinical interventions.

Motor Impairments in Children with Autism Spectrum Disorder: A Systematic Review and Meta-analysis.

This article comprehensively reviews motor impairments in children with autism spectrum disorder (ASD) to: (1) determine the prevalence of motor problems in children with ASD; (2) understand the nature of motor difficulties in ASD and whether they are consistent with developmental coordination disorder (DCD); and (3) determine if the term DCD was used as a co-occurring diagnosis in children with ASD after publication of the DSM-5 in 2013. The following databases were systematically searched: MEDLINE, EMBASE, CINAHL, and PsycINFO from 2010 to December 2021. Articles were included if they: (1) were peer-reviewed and published in a scientific journal; (2) included children with ASD who were between 5 and 12years; (3) used motor or function measures to assess motor abilities in children with ASD. Studies that included children with intellectual disabilities were excluded. Two independent reviewers reviewed titles, abstracts, and full-text articles for inclusion. Twenty-seven studies met the inclusion criteria and wereassessed for quality by two independent reviewers using the Appraisal tool for Cross-Sectional Studies. The majority of articles (92.5%) indicated that 50-88% of children with ASD had significant motor impairments on standardized motor assessments and/or functional questionnaires. The nature of motor and function problems in ASD were consistent with DCD; however, only three out of 20 papers (15%) that were published from 2014 described the motor problems as DCD. One study reported that 15.1% of children with ASD with motor impairments had a co-occurring diagnosis of DCD, suggesting that DCD is under-recognized in this clinical population.

Neuroprotective effects of pre-ischemic exercise are linked to expression of NT-3/NT-4 and TrkB/TrkC in rats

Introduction and objectiveStroke causes irreversible damage, particularly to the hippocampus. Evidence suggests that exercise training may mitigate adverse structural and functional consequences of an ischemic lesion in the brain. The purpose of this study was to investigate the effects of preconditioning exercise on expression of neurotrophic factor genes and proteins in hippocampalCA1 region and their relationship with sensorimotor recovery following global ischemia/reperfusion (Is/Re) injury in a rat model of stroke. MethodsMale Wistar rats were randomly assigned to Exercise+Ischemia/Reperfusion (Ex+Is/Re),Control+Ischemia/Reperfusion (Co+Is/Re), and Sham treatments. Rats in the exercise groups ran on a treadmill for 45 min/d for five days/week for 8 consecutive weeks prior to Is/Re lesion.Ischemia was induced by common carotid artery occlusion (CCAO). The ladder rung walking task was used to assess functional impairments and recovery following ischemic lesion.Tissue from hippocampal area CA1 was inspected for ischemia-induced cell loss and gene and protein expression linked to neurotrophins NT-3, NT-4, and their receptorsTrkB and TrkC. ResultsCCAO caused hippocampal cell death in CA1 and resulted in significant sensori motor impairments in the ladder rung walking task. In contrast, pre-ischemic exercise considerably reduced cell death and supported sensorimotor recovery following CCAO.In addition, NT-3, NT-4,TrkB and TrkC gene expression and their protein levels were significantly increased inthe Ex+Is/Re group compared to Co+Is/Re (p < 0.05). ConclusionThe findings showed that pre-ischemic exercise can exert neuroprotective effects via NT-3 and NT-4 pathways against ischemia in hippocampal CA1 neurons and promote post-injury sensorimotor recovery.

Demands Associated With an Augmentative and Alternative Communication System in Relation to Alternative Forms of Access for Individuals With Motor Impairments

Successful adoption and use of aided augmentative and alternative communication (AAC) must address how to promote fluid, efficient, and organized execution of the motor behavior needed to access the AAC system. A substantial number of people who use AAC have significant motor impairments and require "alternative" access options, such as eye gaze or switch use. Such individuals may be particularly vulnerable to interference from a poorly designed system. However, the inherent demands of alternative access methods have received little direct study. The goal of this tutorial is to offer a clinically and theoretically guided framework for considerations concerning AAC access, with the hope of spurring further discussion and empirical research. A framework that draws upon dynamic systems theory was used to illustrate the interactions between the various elements of importance to AAC access. Information and research from the fields of motor learning, developmental dynamic systems theory, AAC, and assistive technology was integrated into this tutorial to examine their applications for alternative AAC access methods. The framework illustrated that AAC access involves a complex coordination between individual skills, the demands of the communication environment, the activity being undertaken, and the supports and demands inherent in the AAC system itself. Awareness of the many demands that alternative forms of access place on the person who uses them can guide clinicians during assessment and intervention decision making regarding access options for individuals with significant motor impairments. Specific directions for future research are considered.

Renin-angiotensin system in the central nervous system: focus on Huntington's disease.

Renin-angiotensin system in the central nervous system: focus on Huntington's disease.

Assessment of behavioral, neuroinflammatory, and histological responses in a model of rat repetitive mild fluid percussion injury at 2 weeks post-injury.

Repetitive mild traumatic brain injury (rmTBI) is a prominent public health concern, with linkage to debilitating chronic sequelae. Developing reliable and well-characterized preclinical models of rmTBI is imperative in the investigation of the underlying pathophysiological mechanisms, as models can have varying parameters, affecting the overall pathology of the resulting injury. The lateral fluid percussion injury (FPI) model is a reliable and frequently used method of TBI replication in rodent subjects, though it is currently relatively underutilized in rmTBI research. In this study, we have performed a novel description of a variation of the lateral repetitive mild FPI (rmFPI) model, showing the graded acute behavioral impairment and histopathology occurring in response to one, two or four mild FPI (1.25 atm) or sham surgeries, implemented 24h apart. Beam walking performance revealed significant motor impairment in injured animals, with dysfunction increasing with additional injury. Based upon behavioral responses and histological observations, we further investigated the subacute pathophysiological outcomes of the dual FPI (dFPI). Immunoreactivity assessments showed that dFPI led to regionally-specific reductions in the post-synaptic protein neurogranin and increased subcortical white matter staining of the presynaptic protein synaptophysin at 2 weeks following dFPI. Immunohistochemical assessments of the microglial marker Iba-1 showed a striking increase in in several brain regions, and assessment of the astrocytic marker GFAP showed significantly increased immunoreactivity in the subcortical white matter and thalamus. With this study, we have provided a novel account of the subacute post injury outcomes occurring in response to a rmFPI utilizing these injury and frequency parameters, and thereby also demonstrating the reliability of the lateral FPI model in rmTBI replication.