Publications by authors named "Pedro Norat"

Efficient topical drug delivery remains a significant challenge in glaucoma management. Although nanoparticle formulations offer considerable promise, their complex preparation processes, co-delivery issues, and batch consistency have hindered their potential. A scalable fabrication strategy is developed here for preparing solid drug nanoparticles (SDNs) with enhanced drug delivery efficiency.

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Background-: Transplantation of autologous mitochondria into ischemic tissue may mitigate injury caused by ischemia and reperfusion.

Methods-: Using murine stroke models of middle cerebral artery occlusion, we sought to evaluate feasibility of delivery of viable mitochondria to ischemic brain parenchyma. We evaluated the effects of concurrent focused ultrasound activation of microbubbles, which serves to open the blood-brain barrier, on efficacy of delivery of mitochondria.

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Stroke remains a major burden on patients, families, and healthcare professionals, despite major advances in prevention, acute treatment, and rehabilitation. Preclinical basic research can help to better define mechanisms contributing to stroke pathology, and identify therapeutic interventions that can decrease ischemic injury and improve outcomes. Animal models play an essential role in this process, and mouse models are particularly well-suited due to their genetic accessibility and relatively low cost.

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Reperfusion injury is an unfortunate consequence of restoring blood flow to tissue after a period of ischemia. This phenomenon can occur in any organ, although it has been best studied in cardiac cells. Based on cardiovascular studies, neuroprotective strategies have been developed.

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Aniridia is a panocular condition characterized by impaired eye development and vision, which is mainly due to the haploinsufficiency of the paired-box-6 (PAX6) gene. Like what is seen in aniridia patients, Pax6-deficient mice Pax6 exhibit a varied degree of ocular damage and impaired vision. Our previous studies showed that these phenotypes were partially rescued by PD0325901, a mitogen-activated protein kinase kinase (MEK or MAP2K) inhibitor.

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Background And Objective: The goal of this study was to systematically review the usefulness of serum biomarkers in the setting of ischemic stroke (IS) to predict long-term outcome.

Methods: A systematic literature review was performed using the PubMed and MEDLINE databases for studies published between 1986 and 2018. All studies assessing long-term functional outcome (defined as ≥30 days) after IS with respect to serum biomarkers were included.

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Retinal ganglion cells (RGCs) exhibit compartmentalized organization, receiving synaptic inputs through their dendrites and transmitting visual information from the retina to the brain through the optic nerve. Little is known about the structure of RGC axon bundles extending from individual RGC somas to the optic nerve head (ONH) and how they respond to disease insults. We recently introduced visible-light optical coherence tomography fibergraphy (vis-OCTF), a technique for directly visualizing and analyzing mouse RGC axon bundles In this study, we validated vis-OCTF's ability to quantify RGC axon bundles with an increased number of RGCs using mice deficient in BCL2-associated X protein (BAX).

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Objective: The discovery of dural lymphatics has spurred interest in the mechanisms of drainage of interstitial fluid from the CNS, the anatomical components involved in clearance of macromolecules from the brain, mechanisms of entry and exit of immune components, and how these pathways may be involved in neurodegenerative diseases and cancer metastasis. In this study the authors describe connections between a subset of arachnoid granulations (AGs) and the venous circulation via intradural vascular channels (IVCs), which stain positively with established lymphatic markers. The authors postulate that the AGs may serve as a component of the human brain's lymphatic system.

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Low bioavailability of topically applied drugs remains a significant challenge for long-term glaucoma therapy. To enhance drug delivery efficiency, we developed dendrimer gel particles that collectively exhibit structural benefits of dendrimer, hydrogel, and particles, using the inverse emulsion method coupled with the highly efficient aza-Michael addition reaction (IEaMA). This hierarchical approach would maximize the utility of the structural features of existing ocular drug delivery systems.

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Neuroanatomy laboratory training is crucial for the education of neurosurgery residents and medical students. Since the brain is a complex and three-dimensional structure, it is challenging to understand the anatomical relationship of the cortex, internal structures, arteries, and veins without appropriate adjuncts. Several injection agents-including the inks/dyes, latex, polyester, acrylic resins, phenol, polyethylene glycol, and phenoxyethanol-have been explored.

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Mitochondria are fundamental for metabolic homeostasis in all multicellular eukaryotes. In the nervous system, mitochondria-generated adenosine triphosphate (ATP) is required to establish appropriate electrochemical gradients and reliable synaptic transmission. Notably, several mitochondrial defects have been identified in central nervous system disorders.

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The goal of this study was to systematically review functional mapping and reorganization that takes place in the setting of arteriovenous malformations (AVMs) and its potential impact on grading and surgical decision making. A systematic literature review was performed using the PubMed database for studies published between 1986 and 2019. Studies assessing brain mapping and functional reorganization in AVMs were included.

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While full integration of robotic surgery has been achieved in other surgical domains, its transition into neurosurgery has been more prolonged, especially with respect to pituitary surgery. The confined working space and precise maneuvers required in endoscopic endonasal surgery makes development of an efficacious and safe robotic system difficult. Nevertheless, preclinical studies have attempted to demonstrate the feasibility of the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, CA) in both transnasal and transoral approaches.

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Background: Machine learning has emerged as a viable asset in the setting of pituitary surgery. In the past decade, the number of machine learning models developed to aid in the diagnosis of pituitary lesions and predict intraoperative and postoperative complications following transsphenoidal surgery has increased exponentially. As computational processing power continues to increase, big data sets continue to expand, and learning algorithms continue to surpass gold standard predictive tools, machine learning will serve to become an important component in improving patient care and outcomes.

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Glioma continues to be a challenging disease process, making up the most common tumor type within the pediatric population. While low-grade gliomas are typically amenable to surgical resection, higher grade gliomas often require additional radiotherapy in conjunction with adjuvant chemotherapy. Molecular profiling of these lesions has led to the development of various pharmacologic and immunologic agents, although these modalities are not without great systemic toxicity.

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Arteriovenous malformation (AVM) presenting with epilepsy significantly impacts patient quality of life, and it should be considered very much a seizure disorder. Although hemorrhage prevention is the primary treatment aim of AVM surgery, seizure control should also be at the forefront of therapeutic management. Several hemodynamic and morphological characteristics of AVM have been identified to be associated with seizure presentation.

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From their origins as cardiovascular research tools, endovascular techniques have evolved to provide a minimally invasive means of diagnosis and therapy for individuals suffering from occlusive artery disease. The techniques were pioneered by William Harvey, whose work set the stage for all subsequent endovascular experiments. These included the bold self-catheterization procedure performed by Werner Forssmann in 1929, which would lead to his dismissal by his superiors, only to regain respect within the medical community in 1956 on receiving the Nobel Prize.

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Objective: The goal of this study was to systematically review the outcomes of endoscopic endonasal surgery (EES) for pediatric craniopharyngiomas so as to assess its safety and efficacy.

Methods: A systematic literature review was performed using the PubMed and MEDLINE databases for studies published between 1986 and 2019. All studies assessing outcomes following EES for pediatric craniopharyngiomas were included.

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Neuroimaging is an indispensable tool in the workup and management of patients with neurological disorders. Arterial spin labeling (ASL) is an imaging modality that permits the examination of blood flow and perfusion without the need for contrast injection. Noninvasive in nature, ASL provides a feasible alternative to existing vascular imaging techniques, including angiography and perfusion imaging.

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Cortical spreading depression (CSD) is a pathophysiologic phenomenon that describes an expanding wave of depolarization within the cortical gray matter. Originally described over 70 years ago, this spreading depression disrupts neuronal and glial ionic equilibrium, leading to increased energy demands that can cause a metabolic crisis. This results in secondary insult, further perpetuating brain injury and neuronal death.

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Enhanced recovery after surgery (ERAS) is an evidence-based approach developed to ameliorate the patient recovery process following surgical procedures. Employing a multimodal, multidisciplinary approach, ERAS implements strategies and treatment paradigms that have been shown to improve patient outcomes, reduce hospital length of stay, and ultimately reduce healthcare costs. With a substantial body of the literature supporting the implementation of ERAS in other surgical specialties, ERAS has only recently made its foray into spine surgery.

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Resection of intrinsic brainstem tumors is fraught with a high risk of morbidity. In select cases, however, complete tumor resection is possible and can result in long-term benefit to the patient. Informed consent for the operation was obtained.

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