Translational stroke research
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The ischemic penumbra defined four decades ago has been the main battleground of ischemic stroke. The evolving ischemic penumbra concept has been providing insight for the development of vascular and cellular approaches as well as diagnostic tools for the treatment of ischemic stroke. rt-PA thrombolytic therapy to prevent the transition of ischemic penumbra to core has been approved for acute ischemic stroke within 3 h and was later recommended to extend to 4.5 h after symptom onset. Mechanical thrombectomy was introduced for the treatment of acute ischemic stroke with a therapeutic window of up to 24 h after stroke onset. ⋯ Entering the 5th decade since the introduction, ischemic penumbra remains the main focus of ischemic stroke research and clinical practice. In this review, we summarized the evolving ischemic penumbra concept and its implication in the development of vascular and cellular interventions as well as diagnostic tools for acute ischemic stroke. In addition, we discussed future perspectives on expansion of the campaign beyond ischemic penumbra to develop treatment for ischemic stroke.
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Stroke is the second leading cause of death and main cause of disability worldwide, but with few effective therapies. Although stem cell-based therapy has been proposed as an exciting regenerative medicine strategy for brain injury, there are limitations. The developed cerebral organoids (COs) represent a promising transplantation source for stroke that remains to be answered. ⋯ Moreover, COs transplantation promotes predominantly exogenous neurogenesis in the transplantation periphery of ipsilateral cortex and predominantly endogenous neurogenesis in the hippocampus and subventricular zone. Together, we demonstrate the efficacy and underlying mechanisms of COs transplantation in stroke. This preliminary but promising study provides first-hand preclinical evidence for COs transplantation as a potential and effective intervention for stroke treatment.
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Patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) should be triaged to an endovascular-capable hospital by the emergency medical service (EMS). We designed a prehospital LVO prediction scale based on EMS assessments. In the derivation cohort, 1157 patients transferred to our hospital by the EMS because of suspected stroke within 24 h of onset were retrospectively examined. ⋯ In the derivation cohort, with the optimal cut-point of FACE2AD ≥ 3 determined by the area under the curve (AUC; 0.88; 95% confidence interval 0.87-0.90), sensitivity, specificity, positive predictive value, and negative predictive value for FACE2AD to predict LVO were 0.85, 0.80, 0.39, and 0.97, respectively. In the validation cohort, the FACE2AD scale had higher accuracy, with an AUC value of 0.84 for predicting LVO compared with the other scales (all p < 0.01). The FACE2AD scale is a simple, reliable tool for identifying AIS due to LVO by the EMS.
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The COVID-19 pandemic is associated with neurological symptoms and complications including stroke. There is hypercoagulability associated with COVID-19 that is likely a "sepsis-induced coagulopathy" and may predispose to stroke. The SARS-CoV-2 virus binds to angiotensin-converting enzyme 2 (ACE2) present on brain endothelial and smooth muscle cells. ⋯ Angiotensin II is proinflammatory, is vasoconstrictive, and promotes organ damage. Depletion of ACE2 by SARS-CoV-2 may tip the balance in favor of the "harmful" ACE1/angiotensin II axis and promote tissue injury including stroke. There is a rationale to continue to treat with tissue plasminogen activator for COVID-19-related stroke and low molecular weight heparinoids may reduce thrombosis and mortality in sepsis-induced coagulopathy.
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Adult neurogenesis in the subventricular zone is a topic of intense research, since it has vast implications for the fundamental understanding of the neurobiology of the brain and its potential to being harnessed for therapy in various neurological disorders. Investigation of adult neurogenesis has been complicated by the difficulties with characterization of neural stem cells in vivo. However, recent single-cell transcriptomic studies provide more detailed information on marker expression in neural stem cells and their neuronal lineage, which hopefully will result in a more unified discussion. ⋯ While there is ongoing debate about the longevity of active post-natal neurogenesis in humans, the subventricular zone has the capacity to upregulate neurogenesis in response to ischemic stroke. Though, the stroke-induced neurogenesis in humans does not seem to translate into adequate functional recovery, which opens discussion about potential treatment strategies to harness this neuroregenerative response. Various therapeutic approaches are explored in preclinical and clinical studies to target endogenous neurogenesis of which some are discussed in this review.