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Browsing by Subject "Two-photon"

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    In Vivo Wireless Brain Stimulation via Non-invasive and Targeted Delivery of Magnetoelectric Nanoparticles
    (Springer, 2021) Nguyen, Tyler; Gao, Jianhua; Wang, Ping; Nagesetti, Abhignyan; Andrews, Peter; Masood, Sehban; Vriesman, Zoe; Liang, Ping; Khizroev, Sakhrat; Jin, Xiaoming; Anatomy, Cell Biology and Physiology, School of Medicine
    Wireless and precise stimulation of deep brain structures could have important applications to study intact brain circuits and treat neurological disorders. Herein, we report that magnetoelectric nanoparticles (MENs) can be guided to a targeted brain region to stimulate brain activity with a magnetic field. We demonstrated the nanoparticles' capability to reliably evoke fast neuronal responses in cortical slices ex vivo. After fluorescently labeled MENs were intravenously injected and delivered to a targeted brain region by applying a magnetic field gradient, a magnetic field of low intensity (350-450 Oe) applied to the mouse head reliably evoked cortical activities, as revealed by two-photon and mesoscopic imaging of calcium signals and by an increased number of c-Fos expressing cells after stimulation. Neither brain delivery of MENs nor the magnetic stimulation caused significant increases in astrocytes and microglia. Thus, MENs could enable a non-invasive and contactless deep brain stimulation without the need of genetic manipulation.
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    Magneto-Electric Nanoparticles Cobalt Ferrite (CoFe2O4) -- Barium Titanate (BaTiO3) for Non-Invasive Neural Modulations
    (2020-09) Nguyen, Tyler; White, Fletcher; Blesch, Armin; Jin, Xiaoming; Rodgers, Richard; Khizroev, Sakhrat
    Non-invasive brain stimulation is valuable for studying neural circuits and treating various neurological disorders in human. However, current technologies of noninvasive brain stimulation usually have low spatial and temporal precision and poor brain penetration, which greatly limit their application. A new class of nanoparticles known as magneto-electric nanoparticles (MENs) is highly efficient in coupling an externally applied magnetics wave with generating local electric fields for neuronal activity modulation. Here, a new type of MENs was developed that consisted of CoFe2O4- BaTiO3 and had excellent magneto-electrical coupling properties. Calcium imaging technique was used to demonstrate their efficacy in evoking neuronal activity in organotyic and acute cortical slices that expressed GCaMP6 protein. For in vivo noninvasive delivery of MENs to brain, fluorescently labeled MENs were intravenously injected and attracted to pass through blood brain barrier to a targeted brain region by applying a focal magnet field. Magnetic wave (~450 G at 10 Hz) applied to mouse brain was able to activate cortical network activity, as revealed by in vivo two-photon and mesoscopic imaging of calcium signals at both cellular and global network levels. The effect was further confirmed by the increased number of c-Fos expressing cells after magnetic stimulation. Histological analysis indicated that neither brain delivery of MENs nor the subsequent magnetic stimulation caused any significant increases in the numbers of GFAP and IBA1 positive astrocytes and microglia in the brain. MENs stimulation also show high efficacy in short-term pain relieve when tested with a tibial nerve injury mouse model. The study demonstrates the feasibility of using MENs as a novel efficient and non-invasive technique of brain stimulation, which may have great potential for translation.
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    Progressive alterations in microstructural organization and biomechanical response in the ApoE mouse model of aneurysm
    (Taylor & Francis, 2013) Haskett, Darren; Azhar, Mohamad; Utzinger, Urs; Vande Geest, Jonathan P.; Pediatrics, School of Medicine
    AAA is a complex disease that leads to a localized dilation of the infrarenal aorta that develops over years. Longitudinal information in humans has been difficult to obtain for this disease, therefore mouse models have become increasingly used to study the development of AAAs. The objective of this study was to determine any changes that occur in the biomechanical response and fiber microstructure in the ApoE(-/-) AngII mouse model of aneurysm during disease progression. Adult ApoE(-/-) AngII infused mice along with wild-type controls were taken at 14 and 28 d. Aortas were excised and tested simultaneously for biaxial mechanical response and ECM organization. Data sets were fit to a Fung-type constitutive model to give peak strains and stiffness values. Images from two photon microscopy were quantified in order to assess the preferred fiber alignment and degree of fiber orientation. Biomechanical results found significant differences that were present at 14 d had returned to normal by 28 d along with significant changes in fiber orientation and dispersion indicating remodeling occurring within the aneurysmal wall. This return of some of the normal biomechanical function, in addition the continuing changes that occur in the microstructure suggest a restorative response that occurs in the ApoE(-/-) AngII infused model after the initial aneurysm formation.
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