large ischemic stroke

Overview

Large ischemic stroke refers to a severe form of cerebral infarction caused by interruption of blood flow to a substantial territory of the brain, most often from large vessel occlusion with a correspondingly large established infarct core. Clinically, it is associated with high rates of death and long-term disability, and it remains a major cause of morbidity worldwide. In recent research, the term is often used in the context of acute ischemic stroke with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS), reflecting extensive early ischemic injury.

Biologically, large ischemic stroke is not a single-pathway disorder but the end result of the ischemic cascade, involving energy failure, excitotoxicity, oxidative stress, inflammation, autophagy dysregulation, glial activation, blood-brain barrier injury, and secondary hemorrhagic transformation. These processes have motivated studies of neuroprotective strategies and recovery-promoting interventions, including endovascular thrombectomy, adjunctive intra-arterial alteplase, Blood Pressure management, mesenchymal stem cell therapy, electroacupuncture, hypothermia, and experimental agents targeting reactive oxygen species, COX-2-mediated neuroinflammation, mitochondrial dysfunction, and glial scar formation.

Focus of Latest Publications

Recent publications have focused on large ischemic stroke primarily as a high-risk clinical subgroup within acute ischemic stroke, especially patients with large vessel occlusion and established large infarct. One study analyzed the impact of age on outcomes after endovascular therapy for large ischemic stroke, defining the condition by ASPECTS ≤ 5 and highlighting that age-related outcome differences remain unclear. Another secondary analysis from the randomized TENSION trial reported that large core stroke thrombectomy was safe and effective regardless of prior antithrombotic or thrombolytic treatment, supporting the use of endovascular thrombectomy in this population even when patients had already received antithrombotic medication or thrombolysis.

Several studies addressed treatment optimization after reperfusion therapy. The CHOICE-2 randomized clinical trial evaluated adjunctive intra-arterial alteplase after successful thrombectomy for acute ischemic stroke due to large vessel occlusion, motivated by the observation that functional outcomes remain suboptimal despite high recanalization rates with endovascular thrombectomy. A post-hoc analysis of ENCHANTED2/MT found that intensive Blood Pressure lowering to targets below 120 mm Hg worsened functional outcomes after endovascular thrombectomy, reinforcing the importance of careful hemodynamic management after reperfusion. Another study examined immediate angioplasty or stenting in acute ischemic stroke with severe intracranial stenosis, extending the broader question of how best to manage large-vessel pathology when occlusion is not the only issue.

Risk stratification and prognosis were also major themes. A national thrombectomy registry study described stroke progressor phenotypes based on ASPECTS decay and perfusion-estimated infarct growth rate, showing that infarct growth is highly heterogeneous among ischemic stroke patients and has clinical implications. Other work investigated biomarkers and prognostic indicators after ischemic stroke, including Serum glial fibrillary acidic protein, multiple cardiac biomarkers, and a white blood cell-to-hemoglobin ratio model for mortality prediction in critically ill patients. Although not limited to large ischemic stroke, these studies are relevant because large infarcts are especially prone to early neurological deterioration, hemorrhagic transformation, and poor functional recovery.

Prestroke prevention and poststroke recovery were also examined. Comprehensive prestroke risk factor control was studied in relation to 3-month functional outcomes after acute ischemic stroke, while longitudinal adherence to statins and antithrombotic therapy after ischemic stroke was linked to lipid control and cardiovascular outcomes. Additional studies addressed hypertension control after stroke using a phone-based nurse-guided intervention, and physical activity maintenance after stroke or transient ischemic attack. These findings are relevant to large ischemic stroke because secondary prevention and rehabilitation strongly influence long-term outcome in survivors.

Experimental and translational studies explored mechanisms and candidate therapies relevant to large ischemic stroke biology. Human umbilical cord-derived mesenchymal stem cells were tested in a phase 1 trial of intravenous transplantation for ischemic stroke, reflecting interest in cell-based repair strategies. Preclinical studies investigated hydrogen sulfide-releasing Peptides, poliumoside, eupalinolide B, 4-hydroxybenzaldehyde, Curcumae Rhizoma-derived compounds, mild hypothermia, transcranial direct current stimulation, electroacupuncture, and fecal microbiota transplantation from exercise-preconditioned mice. These interventions were studied in relation to oxidative stress, mitochondrial dysfunction, autophagy, microglial M1 polarization, ELAVL1/SIRT1/FOXO1 signaling, PI3K/Akt/GSK3β signaling, and blood-brain barrier integrity, all of which are mechanistically relevant to large ischemic stroke recovery and injury limitation.

Biomarker and diagnostic research also intersected with large ischemic stroke. A chemiluminescent AChE-responsive probe was developed to improve visualization of acute ischemic stroke, and an AI-enhanced nanophotonic heterochain sensor was evaluated for multiplexed biomarker detection across serum, urine, and saliva to differentiate ischemic stroke from intracerebral hemorrhage and healthy controls. Another study assessed temporal patterns and clinical value of serum GFAP in acute ischemic stroke. These approaches reflect the need for rapid, accurate differentiation and prognostication in severe stroke presentations, where time-sensitive decisions about Endovascular Treatment are critical.

Key Publications

• NEWMay Integrating multi-omics analysis to identify potential biomarkers and regulatory networks of ischemic stroke. (Progress in neuro-psychopharmacology & biological psychiatry, 2026, PMID 42167472): "Ischemic stroke (IS) is a leading cause of death and long-term disability worldwide, with a complex and multifactorial pathophysiology that is still incompletely understood."
• NEWJun Association of Esketamine use with mortality and clinical outcomes in patients with cancer-related depression: A target trial emulation. (Progress in neuro-psychopharmacology & biological psychiatry, 2026, PMID 42235877): "The esketamine group also showed a lower risk of ischemic stroke (HR 0.394, 95% CI 0.223-0.698), and subgroup analyses indicated that these observed associations were more pronounced in older patients."
• NEWJun Decoding neuron-specific lineage to identify diagnostic biomarkers and therapeutic targets for ischemic stroke. (iScience, 2026, PMID 42291234): "Ischemic stroke (IS) imposes a major global health burden."
• Jun Balloon-assisted retrieval of detached microwire tip during mechanical thrombectomy. (Journal of neurointerventional surgery, 2026, PMID 41043865): "Mechanical thrombectomy is the standard of care for acute ischemic stroke due to large vessel occlusion."
• Jun Long-Term Outcomes After Ischemic Stroke Across Atrial Fibrillation Phenotypes Defined by Detection Timing and Prior Anticoagulation Status. (Neurology, 2026, PMID 42314108): "Atrial fibrillation (AF)-associated ischemic stroke is often managed as a single clinical entity; however, prognosis may vary depending on whether AF was detected after the stroke or whether the stroke occurred despite prior oral anticoagulant (OAC) use."
• Jun Pathogenic role of serpin B3-positive neutrophils in reinforcing thrombus stiffening during ischemic stroke. (Blood, 2026, PMID 41774516): "The contribution of immune cells to thrombus architecture and mechanical properties in acute ischemic stroke (AIS) remains poorly understood."
• Jun Time-Dependent Association Between Breast Cancer and Risk of Ischemic Stroke: A Nationwide Cohort Study. (Neurology, 2026, PMID 42308440): "We investigated ischemic stroke risk among breast cancer survivors and evaluated associations by age, follow-up duration, and type of cancer treatment."
• Jun The translational potential of drug-induced hypothermia in acute ischemic stroke. (Science translational medicine, 2026, PMID 42308333): "Induction of a hypothermic and hypometabolic state is considered an avenue to treat severe diseases, such as ischemic stroke."
• Jun Intravenous human umbilical cord-derived mesenchymal stem cell transplantation for ischemic stroke (MERIT): A phase 1 trial. (Cell reports. Medicine, 2026, PMID 42208543): "Umbilical cord-derived mesenchymal stem cells (UC-MSCs) hold promise as a potential therapy for ischemic stroke, but the optimal transplantation strategy remains to be explored."
• Jun Longitudinal Trends and Outcomes in Transcatheter Aortic Valve Implantation: a report from the SwissTAVI Registry. (Cardiovascular intervention and therapeutics, 2026, PMID 42298270): "Procedural mortality declined from 2.9% to 1.2%, periprocedural myocardial infarction from 0.4% to 0.2% and stroke from 3.2% to 2.0% (all p<0.001)."