Browsing by Author "Oyarzun, Juan Esteban"

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    Peri-spinal Neurovascular Response Triggered by a Painless Electrical Nerve Stimulation in Patients with Chronic Arterial Hypertension
    (2023) Appelgren, Juan Pablo Gonzalez; Caulier-Cisterna, Raul; Oyarzun, Juan Esteban; Uribe, Sergio; Eblen-Zajjur, Antonio
    PurposeAlterations of the central nervous system are frequent complications in patients with chronic arterial hypertension (AHT). However, functional spinal cord lesions are not often detected in these patients despite diagnostic advances in neuroimaging and electrophysiology. Recently, a new non-invasive functional near infrared spectroscopy (fNIRS) application was developed for assessment of the peri-spinal neurovascular response (NVR) as a functional test of the spinal cord.MethodsThe continuous wave fNIRS technique was applied to detect changes in O(2)Hb concentration during the peri-spinal NVR triggered by non-noxious electrical stimulation of the median nerve at the wrist, and recorded at cervical and thoracic spinal levels using three different stimulation protocols in subjects with AHT treated with losartan (n = 22; 142.14 +/- 133.9 months of disease) and compared to healthy control subjects (n = 37). The body mass index (BMI) and the median nerve conduction velocity (NCV) were also recorded.ResultsThe NVR of patients with AHT showed a significantly lower amplitude (- 70.4%; cervical), longer rise time (+ 22.2%; cervical), and longer duration (+ 28.0%; thoracic) than the control group (p < 0.01). The stimulus intensity-response in the AHT group was - 53.5%, - 55.9%, and - 63% lower in amplitude than the controls (p < 0.05) for the increasing stimulus intensity steps (5; 7.5 and 10 mA, respectively) at the cervical level. Patients with BMI > 30 showed more intense changes. The median NCV was normal for both groups.ConclusionThese data show, for the first time, the difference in peri-spinal NVR between normal subjects and losartan-treated ATH patients, indicating the potential of a non-invasive fNIRS technique to find sensory functional abnormalities of the spinal cord in these patients.
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    The Cervical and Meningeal Lymphatic Network as a Pathway for Retrograde Nanoparticle Transport to the Brain
    (2024) Ramos-Zaldivar, Hector; Polakovicova, Iva; Salas-Huenuleo, Edison; Yefi, Claudia P.; Silva-Ancahuail, David; Jara-Guajardo, Pedro; Oyarzun, Juan Esteban; Neira-Troncoso, Alvaro; Burgos, Patricia, V; Cavieres, Viviana A.; Arias-Munoz, Eloisa; Martinez, Carlos; Riveros, Ana L.; Corvalan, Alejandro H.; Kogan, Marcelo J.; Andia, Marcelo E.
    Introduction: The meningeal lymphatic vessels have been described as a pathway that transports cerebrospinal fluid and interstitial fluid in a unidirectional manner towards the deep cervical lymph nodes. However, these vessels exhibit anatomical and molecular characteristics typical of initial lymphatic vessels, with the absence of surrounding smooth muscle and few or absent valves. Given its structure, this network could theoretically allow for bidirectional motion. Nevertheless, it has not been assessed as a potential route for nanoparticles to travel from peripheral tissues to the brain. Methods: We employed superparamagnetic iron oxide nanoparticles (SPIONs), exosomes loaded with SPIONs, gold nanorods, and Chinese ink nanoparticles. SPIONs were prepared via chemical coprecipitation, while exosomes were isolated from the B16F10 melanoma cell line through the Exo-Spin column protocol and loaded with SPIONs through electroporation. Gold nanorods were functionalized with polyethylene glycol. We utilized C57BL/6 mice for post-mortem and in vivo procedures. To evaluate the retrograde directional flow, we injected each nanoparticle solution in the deep cervical lymph node. The head and neck were fixed for magnetic resonance imaging and histological analysis. Results: Here we show that extracellular vesicles derived from the B16F10 melanoma cell line, along with superparamagnetic iron oxide nanoparticles, gold nanorods, and Chinese ink nanoparticles can reach the meningeal lymphatic vessels and the brain of C57BL/6 mice after administration within the deep cervical lymph nodes post-mortem and in vivo, exclusively through lymphatic structures. Discussion: The functional anatomy of dural lymphatics has been found to be conserved between mice and humans, suggesting that our findings may have significant implications for advancing targeted drug delivery systems using nanoparticles. Understanding the retrograde transport of nanoparticles through the meningeal lymphatic network could lead to novel therapeutic approaches in nanomedicine, offering new insights into fluid dynamics in both physiological and neuropathological contexts. Further research into this pathway may unlock new strategies for treating neurological diseases or enhancing drug delivery to the brain.