Neuroscience
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Ischemic stroke research has enabled significant advancements in diagnosis, treatment, and management of this debilitating disease, yet challenges remain standing in the way of better patient prognoses. In this narrative review, a fictional case illustrates challenges and uncertainties that medical professionals still face - penumbra identification, lack of neuroprotective agents, side-effects of tissue plasminogen activator, dearth of molecular biomarkers, incomplete microvascular reperfusion or no-reflow, post-recanalization hyperperfusion, blood pressure management and procedural anesthetic effects. The current state of the field is broadly reviewed per topic, with the aim to introduce a broad audience (scientist and clinician alike) to recent successes in translational stroke research and pending scientific queries that are tractable for preclinical assessment. Opportunities for co-operation between clinical and experimental stroke experts are highlighted to increase the size and frequency of strides the field makes to improve our understanding of this disease and ways of treating it.
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Stroke is the most common cause of disability. Brain repair mechanisms are often insufficient to allow a full recovery. Stroke damage involve all brain cell type and extracellular matrix which represent the crucial "glio-neurovascular niche" useful for brain plasticity. ⋯ MSC, mononuclear cells (MNC), umbilical cord stem cells and NSC are the most investigated. Innovative approaches are implemented concerning combinatorial approaches with growth factors and biomaterials such as injectable hydrogels which could protect a cell graft and/or deliver drugs into the post-stroke cavity at chronic stages. Through main publications of the last two decades, we provide in this review concepts and suggestions to improve future translational researches and larger clinical trials of cell therapy in stroke.
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The constant failure of new neuroprotective therapies for ischemic stroke has partially halted the search for new therapies in recent years, mainly because of the high investment risk required to develop a new treatment for a complex pathology, such as stroke, with a narrow intervention window and associated comorbidities. However, owing to recent progress in understanding the stroke pathophysiology, improvement in patient care in stroke units, development of new imaging techniques, search for new biomarkers for early diagnosis, and increasingly widespread use of mechanical recanalization therapies, new opportunities have opened for the study of neuroprotection. This review summarizes the main protective agents currently in use, some of which are already in the clinical evaluation phase. It also includes an analysis of how recanalization therapies, new imaging techniques, and biomarkers have improved their efficacy.
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Epidemiological data show that males are more often and/or more severely affected by symptoms of prefrontal cortical dysfunction in schizophrenia, Parkinson's disease and other disorders in which dopamine circuits associated with the prefrontal cortex are dysregulated. This review focuses on research showing that these dopamine circuits are powerfully regulated by androgens. It begins with a brief overview of the sex differences that distinguish prefrontal function in health and prefrontal dysfunction or decline in aging and/or neuropsychiatric disease. ⋯ Candidate mechanisms by which androgens dynamically control mesoprefrontal dopamine systems and impact prefrontal states of hypo- and hyper-dopaminergia in aging and disease are then considered. This is followed by discussion of a working model that identifies a key locus for androgen modulation of mesoprefrontal dopamine systems as residing within the prefrontal cortex itself. The last sections of this review critically consider the ways in which the organization and regulation of mesoprefrontal dopamine circuits differ in the adult male and female brain, and highlights gaps where more research is needed.