Browsing by Author "Dunn, Jeffery F."

Now showing 1 - 7 of 7
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    Detection of inter-hemispheric functional connectivity in motor cortex with coherence analysis
    (European Optical Society, 2012) Varshney, V.P.; Liapounova, N.; Golestani, A. M.; Goodyear, B.; Dunn, Jeffery F.
    Functional near-infrared spectroscopy (fNIRS) is showing promise as an alternate method to fMRI for studying cortical function. Resting state studies in both methods are showing functional linkages. The strength of functional connections is typically quantified by the level of significance of the temporal synchrony between brain regions, termed resting-state functional connectivity. Coherence analysis of resting state allows for phase insensitive and frequency specific analysis. This paper provides a detailed method for undertaking fNIRS in combination with resting-state coherence analysis. We show that maps of inter-hemispheric resting-state functional connectivity between the motor cortices can be reliably generated, and the frequency responses (to 50 Hz) for both oxy- and deoxyhemoglobin. Frequencies of 0-0.1 Hz provide robust data as have been shown previously. Higher frequencies (up to 5 Hz) also exhibit high coherence. Deoxyhemoglobin also shows high coherence above 10Hz. Coherence is similar during both resting and task activated states. fNIRS allows for mapping cortical function and, in combination with coherence analysis, allows one to study variations in frequency response.
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    High altitude exposure and ischemic stroke: A literature review
    (2011) Ortiz-Prado, Esteban; Dunn, Jeffery F.
    Despite our understanding of stroke, the risk factors involved and its treatment and prevention, stroke remains the second leading cause of death among humans worldwide. Several risk factors have been associated with higher incidences of stroke, such as hypertension or diabetes, while non-traditional risk factors such as vitamin D deficiency or cardiac valvular thickness have recently been identified. The potential role of hypoxia or high altitude exposure as a risk factor has not been clearly established. This review includes the relationship between acute and chronic high altitude exposure and the possible development of ischemic stroke in high altitude populations. Several risk factors are identified in high altitude dwellers such as polycythemia, increased platelet adhesiveness and greater risk to develop vascular thrombosis. Other conditions such as dehydration, extreme cold and immobilization might lead to increased risk of ischemic stroke in newcomers. Taking into account the limited number of studies, it is argued that high altitude and chronic hypoxia may be risk factors for the development of ischemic stroke. The altitude associated with higher prevalence of ischemic stroke is not clear, but it appears that there is increased risk above 3000m.
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    Hypoxia and Inflammation-Induced Disruptions of the Blood-Brain and Blood-Cerebrospinal Fluid Barriers Assessed Using a Novel T1-Based MRI Method
    (Springer Verlag, 2016-01) Nathoo, Nabeela; Jalal, Hamza; Natah, Sirajedin S.; Zhang, Qiong; Wu, Ying; Dunn, Jeffery F.
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    Intra-articular injection of synovial mesenchymal stem cells improves cartilage repair in a mouse injury model
    (Nature Publishing Group, 2016-03-17) Mak, J.; Jablonski, C. L.; Leonard, C. A.; Dunn, Jeffery F.; Raharjo, E.; Matyas, J. R.; Biernaskie, J.; Krawetz, R. J.
    Controversy remains whether articular cartilage has an endogenous stem/progenitor cell population, since its poor healing capacity after injury can lead to diseases such as osteoarthritis. In the joint environment there are mesenchymal stem/progenitor cells (MSCs) in the synovial membrane and synovial fluid that can differentiate into cartilage, but it is still under debate if these cells contribute to cartilage repair in vivo. In this study, we isolated a Sca-1 positive, chondrogenesis capable population of mouse synovial MSCs from C57BL6 and MRL/MpJ “super-healer” strains. Intra-articular injection of Sca-1 + GFP + synovial cells from C57BL6 or MRL/MpJ into C57BL6 mice following cartilage injury led to increased cartilage repair by 4 weeks after injury. GFP expression was detected in the injury site at 2 weeks, but not 4 weeks after injury. These results suggest that synovial stem/progenitor cells, regardless of strain background, have beneficial effects when injected into an injured joint. MSCs derived from MRL/MpJ mice did not promote an increased repair capacity compared to MSCs derived from non-healing C57BL6 controls; however, MRL/MpJ MSCs were observed within the defect area at the time points examined, while C57BL6 MSCs were not.
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    Iron in multiple sclerosis: roles in neurodegeneration and repair
    (Nature Publishing Group, 2014-07-08) Stephenson, Erin; Nathoo, Nabeela; Mahjoub, Yasamin; Dunn, Jeffery F.; Yong, V. Wee
    MRI and histological studies have shown global alterations in iron levels in the brains of patients with multiple sclerosis (MS), including increases in the iron stored by macrophages and microglia. Excessive free iron can be toxic, and accumulation of iron in MS has generally been thought to be detrimental. However, iron maintains the integrity of oligodendrocytes and myelin, and facilitates their regeneration following injury. The extracellular matrix, a key regulator of remyelination, might also modulate iron levels. This Review highlights key histological and MRI studies that have investigated changes in iron distribution associated with MS. Potential sources of iron, as well as iron regulatory proteins and the detrimental roles of excessive iron within the CNS, are also discussed, with emphasis on the importance of iron within cells for oxidative metabolism, proliferation and differentiation of oligodendrocytes, and myelination. In light of the beneficial and detrimental properties of iron within the CNS, we present considerations for treatments that target iron in MS. Such treatments must balance trophic and toxic properties of iron, by providing sufficient iron levels for remyelination and repair while avoiding excesses that might overwhelm homeostatic mechanisms and contribute to damage.
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    Monitoring angiogenesis using a human compatible calibration for broadband near-infrared spectroscopy
    (Society of Photo-optical Instrumentation Engineers (SPIE), 2013-01) Yang, Runze; Zhang, Qiong; Wu, Ying; Dunn, Jeffery F.
    Angiogenesis is a hallmark of many conditions, including cancer, stroke, vascular disease, diabetes, and high-altitude exposure. We have previously shown that one can study angiogenesis in animal models by using total hemoglobin (tHb) as a marker of cerebral blood volume (CBV), measured using broadband near-infrared spectroscopy (bNIRS). However, the method was not suitable for patients as global anoxia was used for the calibration. Here we determine if angiogenesis could be detected using a calibration method that could be applied to patients. CBV, as a marker of angiogenesis, is quantified in a rat cortex before and after hypoxia acclimation. Rats are acclimated at 370-mmHg pressure for three weeks, while rats in the control group are housed under the same conditions, but under normal pressure. CBV increased in each animal in the acclimation group. The mean CBV (%volume∕volume) is 3.49% 0.43% (mean SD) before acclimation for the experimental group, and 4.76% 0.29% after acclimation. The CBV for the control group is 3.28% 0.75%, and 3.09% 0.48% for the two measurements. This demonstrates that angiogenesis can be monitored noninvasively over time using a bNIRS system with a calibration method that is compatible with human use and less stressful for studies using animals.
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    Therapeutic activation of macrophages and microglia to suppress brain tumor-initiating cells
    (Nature Publishing Group, 2013-12-08) Sarkar, Susobhan; Doring, Axinia; Zemp, Franz J; Silva, Claudia; Lun, Xueqing; Wang, Xiuling; Kelly, John; Hader, Walter; Hamilton, Mark; Mercier, Philippe; Dunn, Jeffery F.; Kinniburgh, Dave; van Rooijen, Nico; Robbins, Stephen; Forsyth, Peter; Cairncross, Gregory; Weiss, Samuel; Yong, V Wee
    Brain tumor initiating cells (BTICs) contribute to the genesis and recurrence of gliomas. We examined whether the microglia and macrophages that are abundant in gliomas alter BTIC growth. We found that microglia derived from non-glioma human subjects markedly mitigated the sphere-forming capacity of glioma patient–derived BTICs in culture by inducing the expression of genes that control cell cycle arrest and differentiation. This sphere-reducing effect was mimicked by macrophages, but not by neurons or astrocytes. Using a drug screen, we validated amphotericin B (AmpB) as an activator of monocytoid cells and found that AmpB enhanced the microglial reduction of BTIC spheres. In mice harboring intracranial mouse or patient-derived BTICs, daily systemic treatment with non-toxic doses of AmpB substantially prolonged life. Notably, microglia and monocytes cultured from glioma patients were inefficient at reducing the sphere-forming capacity of autologous BTICs, but this was rectified by AmpB. These results provide new insights into the treatment of gliomas.