Neuroscience
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Focal brain damage and neurological deficits are the direct consequences of acute ischemic stroke (AIS). In addition, cerebral ischemia causes systemic alterations across peripheral organs. Dysregulation of the autonomic and endocrine systems as well as the release of brain-derived pro-inflammatory mediators trigger a peripheral immune response and systemic inflammation. ⋯ The closely linked lipid metabolism could regulate both glucose and glutathione homeostasis. In addition, increased hepatic very low-density lipoprotein (VLDL) secretion may improve the availability of phospholipids, polyunsaturated fatty acids (PUFAs) and glutathione after AIS. This review provides an overview of recent findings concerning ischemic stroke and the liver and discusses the therapeutic potential of targeting the hepatic metabolism to improve patient outcome after stroke.
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Microglia represent the main immune cell population in the CNS with unique homeostatic roles and contribution to broad neurological conditions. Stroke is associated with marked changes in microglial phenotypes and induction of inflammatory responses, which emerge as key modulators of brain injury, neurological outcome and regeneration. ⋯ While the growing toolkit for microglia manipulation increasingly allows targeting inflammatory pathways in a cell-specific manner, reconsideration of some effects devoted to microglia may also be required. This may particularly concern the interpretation of inflammatory mechanisms that emerge in response to stroke as a form of sterile injury and change markedly in chronic inflammation and common stroke comorbidities.
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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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Despite recent advances in acute stroke management, most patients experiencing a stroke will suffer from residual brain damage and functional impairment. Addressing those residual deficits would require neurorestoration, i.e., rebuilding brain tissue to repair the structural brain damage caused by stroke. However, there are major pathobiological, anatomical and technological hurdles making neurorestorative approaches remarkably challenging, and true neurorestoration after larger ischemic lesions could not yet be achieved. ⋯ This review gives a detailed explanation of the major hurdles so far preventing the achievement of neurorestoration after stroke. It will also describe novel concepts and advancements in biomaterial science, brain organoid culturing, and animal modeling that may enable the investigation of post-stroke neurorestorative approaches in translationally relevant setups. Finally, there will be a review of recent achievements in experimental studies that have the potential to be the starting point of research and development activities that may eventually bring post-stroke neurorestoration within reach.
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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.