Browsing by Subject "Stroke"
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Item An analysis of modular patterns in healthy and post-stroke hemiparetic gait(2014-08) Routson, Rebecca Linn; Neptune, Richard R.Recent studies have suggested the biomechanical subtasks of walking can be produced using a reduced set of co-excited muscles or modules. Individuals post-stroke often exhibit poor inter-muscular coordination characterized by poor timing and merging of modules that are normally independent in healthy individuals. However, whether locomotor therapy can influence module quality (timing and composition) and whether these improvements lead to improved walking performance is unclear. Further, it is unknown whether the same modules that produce self-selected walking can also produce the execution of different mobility tasks. In this study, experimental analyses were used to compare module quality pre- and post-therapy. In subjects with four modules pre- and post-therapy, locomotor training resulted in improved timing of the ankle plantarflexor module and a more extended paretic leg angle that allowed the subjects to walk faster with more symmetrical propulsion. In addition, subjects with three modules pre-therapy increased their number of modules and improved walking performance post-therapy. Thus, locomotor training was found to influence module composition and timing, which can lead to improvements in walking performance. Experimental and simulation analyses were then used to characterize modular organization in specific mobility tasks (walking at self-selected speed with maximum cadence, maximum step length, and maximum step height). We found that the same underlying modules (number and composition) in each subject that contribute to steady-state walking also contribute to the different mobility tasks. In healthy subjects, module timing, but not composition, changed when the task demands were altered. This adaptability in module timing, in addition to the ability to adapt to the changing task demands, was limited in the post-stroke subjects. The primary difference in the execution of the walking biomechanical subtasks occurred in the control of the leg during pre-swing and swing. To increase cadence, the ankle plantarflexors and dorsiflexors contributed more power to the ipsilateral leg in pre-swing and swing, respectively. To increase step height, the hamstrings provided energy to the ipsilateral leg that accelerated the leg into swing in pre-swing and swing. These results provide a first step towards linking impaired module patterns to mobility task performance in persons post-stroke.Item Assessing Visuospatial Neglect in Children with Brain Injury(2014-05-28) Wahlberg, Andrea ChristineVisuospatial neglect (VSN), the failure to report, respond, or orient to novel or meaningful visual stimuli presented in a specific location, is a frequently occurring outcome following stroke. VSN can negatively impact the functions of daily life and is an important predictor for long term outcomes. The phenomenon is frequently studied in adult populations; however, the nature and incidence of VSN following childhood stroke is virtually unknown. Current research investigating the neuroanatomical correlates of VSN and hypothesized models of dysfunction all assume a fully mature brain and thus lack a developmental perspective. Similarly, current neuropsychological measures used to assess VSN are almost exclusively developed and normed with adult populations. While some individual adult tests have been modified for use with children, no standardized battery to assess VSN in young children currently exists. The present study investigated the reliability and validity of a five-task neuropsychological testing battery, the Pediatric Visuospatial Neglect Battery, developed at the Children?s Hospital of Philadelphia (CHOP) to assess VSN in young children ages 2-6 following stroke. Although there were some exceptions, the reliability estimates of task scores obtained from the present sample were generally low. With regard to criterion-related validity, sensitivity to detect brain injury was generally poor while specificity was high. Some of the low reliability and validity estimates were due to measurement problems of the calculated variables. These variables can be reexamined and likely improved in future studies. In other instances, modifications to the tasks are recommended. Specific recommendations for improving the five existing tasks are provided as well as suggestions for additional tasks that could potentially be added to the battery in future administrations. Although somewhat disappointing, low initial reliability and validity estimates are part and parcel to test development. This study represents an important first step in developing a standardized battery to detect VSN in children. With refinement and additional testing, the Pediatric Visuospatial Neglect Battery may soon become an excellent instrument for investigating the VSN phenomenon in children.Item Bayesian forecasting of motor recovery following cortical infarcts(2015-12) Woodie, Daniel Aaron; Walker, Stephen G., 1945-; Jones, TheresaGlobally, about 15 million people suffer a stroke each year. Of these affected, about 5 million die and another 6 million are left with long-term disability. The cause of this disability is often due to motor, or muscle, impairments that make everyday tasks like walking or opening a door difficult or even impossible. Improvements in motor function after an injury is due in large part to reorganization of spared neural tissue. To better understand the physiological changes relevant to recovery of motor function, experimental stroke models have been developed. Many studies have focused on neural reorganization as it relates to improvements in motor function following stroke but little has been done to explore the neurovascular remodeling as it relates to these alterations in motor function. To better understand the relationship between restoration of cortical blood flow and improvements in motor function, we first developed a mouse model of stroke that results in recoverable forelimb impairments and then construct statistical models to best link stroke severity and functional outcomes.Item The coordinated plasticity of astrocytes and synapses in learning and post-stroke recovery(2011-05) Kim, Soo Young, 1980-; Jones, Theresa A.; Gore, Andrea C.; Harris, Kristen M.; Schallert, Timothy; Delville, YvonStroke typically occurs in one hemisphere and often results in long-term disability in the contralateral body side (paretic side). Greater reliance on the non-paretic body side is used to compensate for this disability. Meanwhile, the brain undergoes degenerative and plastic changes in both hemispheres. Many previous studies have investigated post-stroke brain plasticity, and explored how it is shaped by behavioral experiences, to better understand the mechanisms of functional recovery. However, these studies have primarily focused on neurons and synapses. Given the abundant evidence that astrocytes actively control activity and plasticity of synapses, it seems reasonable to investigate how astrocytes are involved in behavior- and injury-driven brain plasticity. The central hypothesis of these studies is that synaptic plasticity underlying motor skill learning and post-stroke motor rehabilitation is coordinated with structural and functional plasticity of perisynaptic astrocytes. This was tested in a rat model of motor learning and "re-learning" after unilateral stroke-like damage to sensorimotor cortex. In the contralesional homotopic cortex, astrocytic volume varied with lesion size, as did the number of synapses. In the remaining motor cortex of the injured hemisphere, rehabilitative training with the paretic limb increased the proportion of astrocytic membrane apposed with synapses along with density of synapses. Furthermore, the percentage of synapses with astrocytic contacts was significantly correlated with functional outcome. Training with the non-paretic limb also induced greater synaptic density than controls in peri-infarct cortex, but functional outcome was negatively correlated with this and was not correlated with astrocytic contacts with synapses. These findings suggest that plasticity of, and association between, synapses and astrocytes vary with the type of experiences. Moreover, pharmacological upregulation of astrocytic glutamate uptake, which is one of the key ways that astrocytes modulate synaptic activity, interfered with functional recovery, supporting a critical role for astrocytic glutamate uptake in functional outcome following a stroke. Taken together, these studies contribute to better understanding of how lesions and experiences affect plasticity of astrocytes and synapses. These findings suggest that post-injury experiences alter astrocytic association with synapses, and that the coordinated plasticity of astrocytes and synapses is likely to be a critical mediator to functional outcome.Item Cortical hemodynamics and motor recovery after cortical infarcts(2015-05) Woodie, Daniel Aaron; Jones, Theresa A.; Dunn, Andrew KStroke is the leading cause of disability and the fourth leading cause of death in the United States. Of those that survive a stroke, many are left with long term functional motor impairments. Spontaneous recovery of motor function occurs after a stroke and the reorganization of spared neural tissue is a contributing factor. To study motor recovery following a stroke, rodent models have been especially useful because experimental manipulations can be paired with controlled infarcts to understand physiologically relevant changes. For example, stroke to the sensory-motor cortex (SMC) in mice produces functional motor impairments which are dependent on the reorganization of the remaining cortex. Ironically, after about 20 years of research on the reorganization of the peri-lesion following cortical ischemia, there has been a lack of focus on the neuro-vascular changes as they relate to functional outcome after stroke. The central hypothesis of this report is that spontaneous vascular remodeling contributes to behavioral recovery and cortical reorganization following ischemic insult. To investigate the relationship between blood flow recovery and improvement of motor function after an ischemic insult, we developed a mouse model of upper extremity impairment after a stroke that can be repeatedly imaged in vivo. Specifically, 14 C57/BL6 mice either received photo-thrombotic cortical lesions (n=7) or vehicle procedures (n=7), were allowed 3 days to recover, and then received forelimb function probes using the pasta matrix reaching task (PMRT), an assay for skilled forelimb function, in tandem with the imaging of cortical blood flow using multi-exposure speckle imaging (MESI) at Days 3, 5, 10, and 20. Results indicate that the mice that received injections with Rose Bengal displayed significantly decreased performance on the PMRT and a significantly reduced amount of cortical blood flow compared to both their baseline performance and the control group. Skilled forelimb performance following the ischemic lesion correlated strongly with stroke severity (as indexed by cortical blood flow in the lesion core 2 hours following lesion induction). Additionally, the re-establishment of cortical blood flow to the infarct core precedes the recovery of motor performance, indicating potential importance for the re-establishment of blood flow to support the adaptive plasticity required for motor recovery.Item Diacylglycerol, novel protein kinase C isozymes [eta] and [theta], and other diacylglycerol activated proteins promote neuroprotective plasmalemmal sealing in B104 neurons in vitro and rat sciatic nerve axons in vivo(2012-12) Zuzek, Aleksej; Bittner, George D.; Ben-Yakar, Adela; Dalby, Kevin N; Thompson, Wesley J; Zakon, Harold HTo survive, neurons and other eukaryotic cells must rapidly repair (seal) plasmalemmal damage. Such repair occurs by an accumulation of intracellular vesicles at or near the plasmalemmal disruption. Diacylglycerol (DAG)-dependent and cAMP-dependent proteins are involved in many vesicle trafficking pathways. Although recent studies have implicated the signaling molecule cAMP in sealing, no study has investigated how DAG and DAG-dependent proteins affect sealing and, whether pharmacological inhibition of such proteins could promote immediate repair of damaged mammalian axons. To this end, I investigated the role of DAG, protein kinase C (PKC) and other DAG-activated proteins in plasmalemmal sealing in B104 neurons in vitro and rat sciatic nerves in vivo. Using dye exclusion to assess Ca2+-dependent vesicle-mediated sealing of transected neurites of individually identifiable rat hippocampal B104 cells, I now report that, compared to non-treated controls, sealing probabilities and rates are increased by DAG and cAMP analogs that activate PKC and Munc13-1, and protein kinase A (PKA). Sealing is decreased by inhibiting DAG-activated novel protein kinase C isozymes η (nPKCη) and θ (nPKCθ) and, Munc13-1, the PKC effector myristoylated alanine rich PKC substrate (MARCKS) or phospholipase C (PLC). DAG-increased sealing is prevented by inhibiting MARCKS or PKA. Sealing probability is further decreased by simultaneously inhibiting nPKCη, nPKCθ and PKA. Extracellular Ca2+, DAG or cAMP analogs do not affect this decrease in sealing. I also report that applying inhibitors of nPKC and PKA to rat sciatic axons crush-severed in vivo under physiological calcium, do not promote immediate repair by polyethylene glycol (PEG), as assessed by compound action potential conduction and dye diffusion through crush sites. These and other data suggest that DAG increases sealing through MARCKS and that nPKCη, nPKCθ and PKA are all required to seal plasmalemmal damage in B104 neurons, and likely all eukaryotic cells.Item Post-stroke aphasia rehabilitation : a review of the history and findings for constraint-induced therapy(2013-05) Benning, Caroline Catherine; Marquardt, Thomas P.Constraint-induced (CI) therapy is an approach adapted from motor rehabilitation to treat language deficits in individuals with poststroke aphasia. The principles of CI therapy were established from behavioral research with animal models that were later applied to human neurorehabilitation. There is a substantial body of evidence to support CI therapy for the treatment of postroke motor deficits; however, evidence for CI aphasia therapy is less established. This report examines the history and current state of evidence for the use of CI-based therapy to treat adults with poststroke aphasia.Item Transcallosal axonal sprouting patterns after ischemic motor cortical lesions and varying forelimb experiences(2014-05) Lubs, Jessica Leighila; Jones, Theresa A.In rodent models of motor cortical stroke, skill learning with the non-paretic forelimb worsens rehabilitation outcomes of the paretic forelimb. The neural basis of this effect is not fully understood. A possible mechanism for this effect is activity-dependent synaptic competition between projections from remaining regions of the ipsi- and contralesional motor cortex, specifically from the ipsilesional rostral forelimb area (RFA) and the contralesional caudal forelimb area (CFA). Previous studies have found that this effect is negated by callosal transections or inhibition of the contralesional cortex, suggesting that the contralesional hemisphere plays a key role. The purpose of this study was to investigate the influence of differential forelimb experience on the cortical plasticity of callosal projections from the contralesional CFA, which is known to contribute to the reinnervation of peri-lesion cortex. Since axonal sprouting is activity dependent, one would expect animals trained with the non-paretic forelimb to have an increase in axonal fibers and bouton densities from the contralesional CFA. Adult male Long-Evans rats were trained to proficiency using their dominant (for reaching) forelimb on the single-pellet-retrieval skilled reaching task. Animals subsequently received unilateral cortical ischemic lesions in the CFA of the hemisphere contralateral to the trained forelimb. On post-infarct day five, rats began 15 days of reach training either with their non-paretic forelimb (NPT), their paretic forelimb (rehabilitation training, RT), or no-training control procedures (CTRL). On post-infarct day 23 all animals received an injection of biotinylated dextran amine (BDA) into the contralesional CFA to label callosal projections from the spared hemisphere into peri-infarct motor cortex. Contrary to the hypothesis, results indicate no significant differences in axonal fiber or synaptic bouton densities across any of the groups within any of the examined regions of peri-lesion cortex. This suggests that the mechanism behind the detrimental effects of NPT on the paretic limb does not involve a net change in densities of neural connections from the contralesional CFA. Future research should explore possible changes in the structure of synapses or variations in relative densities of excitatory and inhibitory post-synaptic cells as possible contributors to the neural basis of the deleterious effect of NPT.Item Understanding dynamic balance during walking using whole-body angular momentum(2014-08) Vistamehr, Arian; Neptune, Richard R.Maintaining dynamic balance during walking is a major challenge in many patient populations including older adults and post-stroke hemiparetic subjects. To maintain dynamic balance, whole-body angular-momentum has to be regulated through proper foot placement and generation of the ground-reaction-forces. Thus, the overall goal of this research was to understand the mechanisms and adaptations used to maintain dynamic balance during walking by analyzing whole-body angular-momentum, foot placement and ground-reaction-forces in older adults and post-stroke subjects. The analysis of healthy older adults showed that they regulated their frontal-plane angular-momentum poorly compared to the younger adults. This was mainly related to the increased step width, which when combined with the dominant vertical ground-reaction-force, created a higher destabilizing external moment during single-leg stance. The results also suggested that exercise programs targeting appropriate foot placement and lower extremity muscle strengthening, particularly of the ankle plantarflexors and hip abductors, may enhance balance control in older adults. During post-stroke hemiparetic walking, ankle-foot-orthosis and locomotor therapy are used in an effort to improve the overall mobility. However, the analyses of healthy subjects walking with and without a solid ankle-foot-orthosis showed that they can restrict ankle plantarflexor output and limit the successful regulation of angular-momentum and generation of forward propulsion. Thus, the prescription of solid ankle-foot-orthosis should be carefully considered. The analysis of hemiparetic subjects walking pre- and post-therapy showed that locomotor training did not improve dynamic balance. However, for those subjects who achieved a clinically meaningful improvement in their self-selected walking speed, their change in speed was correlated with improved dynamic balance. Also, improved balance was associated with narrower mediolateral paretic foot placement, longer anterior nonparetic steps, higher braking ground-reaction-force peaks and impulses, higher (lower) propulsive ground-reaction-force peaks and impulses from the paretic (nonparetic) leg, and higher vertical ground-reaction-force impulses from both legs during the late stance. Further, simulation analyses of hemiparetic walking highlighted the importance of ankle plantarflexors, knee extensors and hip abductors in maintaining balance and revealed the existence of compensatory mechanisms due to the paretic leg muscle weakness. Collectively, these studies showed the importance of ankle plantarflexors and hip abductors in maintaining dynamic balance.Item Women's early symptom experience of stroke : a narrative study(2010-05) Beal, Claudia Calle; Stuifbergen, Alexa K.; Becker, Heather; Harrison, Tracie; Pennebaker, James; Volker, DeborahThe purpose of this study was to gain understanding of the early symptom experience of ischemic stroke in women. This is the only study of which the researcher is aware in which narrative inquiry was used to examine the period of time from symptom onset until emergency department arrival in women. Data collection was achieved by in-depth interviews during which participants’ stories of stroke were elicited. Individual narrative accounts were created and analyzed using within and across case techniques. The participants were nine women ranging in age from 24-86 years (average age 53). Four participants were Caucasian, three were Hispanic, one was African American and one woman was of mixed race. The participants experienced the onset of stroke as the inability to carry out accustomed activities in usual ways. There was a tendency to objectify the body. Only two participants considered stroke as a possible cause for their symptoms, and the other women attributed symptoms everyday bodily experiences and/or other health conditions. Most participants did not perceive themselves at risk for stroke although all but one woman had risk factors. The participants displayed a variety of responses to symptoms, including trying to continue with usual activities and seeking help as well as deciding not to tell anyone about their symptoms. Symptom response was related to women’s evaluation of and emotional response to symptoms. The actions taken by the participants in response to symptoms were informed by the meaning of the symptoms, and meaning was formed within the context of each woman’s life situation. Few women made the decision to seek medical care on their own, and in every case family members or co-workers were reported to take an active role in getting the participant to the hospital. Some family members were reported to consult with one another before making the decision to call EMS or transporting the participant to the emergency department. Consistent with what was expected from extant research the majority of the participants did not arrive at the hospital in time to be offered treatment with t-PA. Recommendations for future research, stroke education and practice were discussed.