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- Creators: School of Life Sciences
- Creators: Wolf, Steven L.
Description
Traumatic brain injury (TBI)—sudden impact or acceleration trauma to the head—is a major cause of death and disability worldwide and is particularly amplified in pediatric cases. TBI is the leading cause of mortality and morbidity in children and adolescents. Adolescence is a critical time where the brain undergoes cognitive development and brain injury-induced disruptions to these processes can lead to life-long debilitating morbidities. The aim of this study was to determine if exercising spatial and contextual memory circuits using a novel rehabilitation strategy called Peg Forest Rehabilitation (PFR) could mitigate the onset of injury-induced cognitive deficits in juvenile rats subjected to diffuse TBI. The PFR aims to synthesize neuroplasticity-based enrichment to improve cognitive outcomes after TBI. We hypothesized that PFR treatment would mitigate the onset of brain injury-induced cognitive deficits and reduce neuroinflammation. Juvenile male Sprague-Dawley rats (post-natal day 35) were subjected to diffuse traumatic brain injury via midline fluid percussion injury or a control surgery. One-week post-injury, rats were exposed to PFR or cage control exploration (15 min/day). PFR allowed free navigation through random configuration of the peg-filled arena for 10 days over 2 weeks. Control rats remained in home cages in the center of the arena with the peg-board removed for 15 min/day/10 days. One-week post-rehabilitation (one-month post-injury), cognitive performance was assessed for short-term (novel object recognition; NOR), long-term (novel location recognition; NLR), and working (temporal order recognition; TOR) memory performance, calculated as a discrimination index between novel and familiar objects. Tissue was collected for immunohistochemistry and stained for ionized calcium binding proteins (Iba-1) to visualize microglia morphology, and somatostatin. PFR attenuated TBI-induced deficits on the NOR task, where the TBI-PFR treatment group spent significantly more time with the novel object compared with the familiar (*p=0.0046). Regardless of rehabilitation, brain-injured rats had hyper-ramified microglia in the hypothalamus indicated by longer branch lengths and more endpoints per cell compared with uninjured shams. Analysis of somatostatin data is ongoing. In this study, passive, intermittent PFR that involved dynamic, novel spatial navigation, prevented TBI-induced cognitive impairment in adolescent rats. Spatial navigation training may have clinical efficacy and should be further investigated.
ContributorsAftab, Umar (Author) / Rowe, Rachel K. (Thesis director) / Newbern, Jason M. (Thesis director) / Ortiz, J. Bryce (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Vascular inflammation is a key component for cerebrovascular disease and ischemic injury is suggested to be a significant contributor, resulting in either myocardial ischemia or stroke. A strong inflammatory response is characterized by the release of inflammatory cytokines, thus producing and/or activating pro-inflammatory proteins in the cell. Our previous studies have demonstrated that hypoxia plus glucose deprivation (HGD), an in vitro model of ischemia, increases the proinflammatory mediator, cyclooxygenase-2 levels (COX-2), in vascular tissues. Nuclear factor kappa B (NF-κB) activation is an upstream transcription factor of COX-2 and had been suggested to be involved in “sterile” inflammation in experimental stroke models. Mechanisms underlying the development and progression of inflammation in the cerebrovasculature following ischemic injury in human tissue has not been addressed. Thus, the purpose of this study was to examine the impact of HGD on NF-κB expression and activation in human brain vascular smooth muscle cells (HBVSMC). In addition, we assessed pro-inflammatory mediator levels of downstream NF-κB transcription products, COX-2 and iNOS, and level of its upstream receptor, TLR4. Primary HBVSMC at passage 7 were treated with normoxia (room air) or HGD (1% O2). Following exposure to HGD (3h), cells were isolated, homogenized, and total protein content determined. Lysates, either whole cell or nuclear and cytosolic fractions, were prepped for western blot and analysis. Anti-α-smooth muscle actin was used to verify HBVSMC origin and -actin was used as a loading control. NF-κBp65, phosphorylated NF-κBp65, COX-2, and TLR4 protein levels were all measured post HGD. NF-κBp65 total protein was expressed in HBVSMC and a trend for an increase in levels following HGD was observed. Indirect activation of pNF-kBp65 was assessed via nuclear fractionation studies and was increased following HGD. Lamin AC was used to verify nuclear fractionation. Additional findings suggested that HBVSMC expressed TLR4 however, total protein levels of TLR4 were not altered by HGD. COX-2 and iNOS protein levels were also increased following HGD. In conclusion, these studies indicate that HGD alters proinflammatory enzyme levels, potentially by altering NF-κBp65 activation in human vascular smooth muscle cells. Funding Support: University of Arizona Sarver Heart Center and University of Arizona Valley Research Project Grant VRP P1 (RG).
ContributorsRahman, Sanna (Author) / Sweazea, Karen (Thesis director) / Gonzales, Rayna (Committee member) / Li, Yu-Jing (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
As the application of interactive media systems expands to address broader problems in health, education and creative practice, they fall within a higher dimensional space for which it is inherently more complex to design. In response to this need an emerging area of interactive system design, referred to as experiential media systems, applies hybrid knowledge synthesized across multiple disciplines to address challenges relevant to daily experience. Interactive neurorehabilitation (INR) aims to enhance functional movement therapy by integrating detailed motion capture with interactive feedback in a manner that facilitates engagement and sensorimotor learning for those who have suffered neurologic injury. While INR shows great promise to advance the current state of therapies, a cohesive media design methodology for INR is missing due to the present lack of substantial evidence within the field. Using an experiential media based approach to draw knowledge from external disciplines, this dissertation proposes a compositional framework for authoring visual media for INR systems across contexts and applications within upper extremity stroke rehabilitation. The compositional framework is applied across systems for supervised training, unsupervised training, and assisted reflection, which reflect the collective work of the Adaptive Mixed Reality Rehabilitation (AMRR) Team at Arizona State University, of which the author is a member. Formal structures and a methodology for applying them are described in detail for the visual media environments designed by the author. Data collected from studies conducted by the AMRR team to evaluate these systems in both supervised and unsupervised training contexts is also discussed in terms of the extent to which the application of the compositional framework is supported and which aspects require further investigation. The potential broader implications of the proposed compositional framework and methodology are the dissemination of interdisciplinary information to accelerate the informed development of INR applications and to demonstrate the potential benefit of generalizing integrative approaches, merging arts and science based knowledge, for other complex problems related to embodied learning.
ContributorsLehrer, Nicole (Author) / Rikakis, Thanassis (Committee member) / Olson, Loren (Committee member) / Wolf, Steven L. (Committee member) / Turaga, Pavan (Committee member) / Arizona State University (Publisher)
Created2014
Description
Stroke is a leading cause of disability with varying effects across stroke survivors necessitating comprehensive approaches to rehabilitation. Interactive neurorehabilitation (INR) systems represent promising technological solutions that can provide an array of sensing, feedback and analysis tools which hold the potential to maximize clinical therapy as well as extend therapy to the home. Currently, there are a variety of approaches to INR design, which coupled with minimal large-scale clinical data, has led to a lack of cohesion in INR design. INR design presents an inherently complex space as these systems have multiple users including stroke survivors, therapists and designers, each with their own user experience needs. This dissertation proposes that comprehensive INR design, which can address this complex user space, requires and benefits from the application of interdisciplinary research that spans motor learning and interactive learning. A methodology for integrated and iterative design approaches to INR task experience, assessment, hardware, software and interactive training protocol design is proposed within the comprehensive example of design and implementation of a mixed reality rehabilitation system for minimally supervised environments. This system was tested with eight stroke survivors who showed promising results in both functional and movement quality improvement. The results of testing the system with stroke survivors as well as observing user experiences will be presented along with suggested improvements to the proposed design methodology. This integrative design methodology is proposed to have benefit for not only comprehensive INR design but also complex interactive system design in general.
ContributorsBaran, Michael (Author) / Rikakis, Thanassis (Thesis advisor) / Olson, Loren (Thesis advisor) / Wolf, Steven L. (Committee member) / Ingalls, Todd (Committee member) / Arizona State University (Publisher)
Created2014