Ischaemic stroke is responsible for significant morbidity and mortality. Reperfusion therapy with intravenous thrombolysis is used to improve outcomes in patients with acute ischaemic stroke within 4.5 hours of symptom onset, but is generally contraindicated in early recurrent ischaemic stroke. Despite this, cases have been reported of patients who have had repeated thrombolysis using alteplase and achieved a good outcome. Tenecteplase, a variant of alteplase with higher specificity for fibrin and a longer half-life, is increasingly used as an alternative thrombolytic agent. However, there are no previously reported cases of repeated thrombolysis using tenecteplase. Here we report the first case of a 69-year-old male patient who received repeated thrombolysis with tenecteplase, rather than alteplase, in early recurrent ischaemic stroke.

Urokinase is often regarded as an older thrombolytic displaced by fibrin-selective agents in reperfusion medicine. Yet its decline has been uneven. This mini-review reframes its contemporary role through three determinants: route, compartment, and access. The systemic role of native urokinase has receded, particularly in stroke. Adjunctive thrombolysis after endovascular reperfusion remains unsettled: POST-UK and POST-TNK were neutral, whereas PEARL and ANGEL-TNK reported higher 90-day excellent-outcome rates. Trial differences preclude a uniform conclusion or generalization to primary intra-arterial thrombolysis and local fibrinolysis. Native urokinase retains a niche when delivered directly into clot-containing compartments or established catheters, including intracranial blood collections, chronic subdural hematoma, selected venous thromboembolism, loculated pleural disease, and catheter-related thrombotic dysfunction. In these settings, it functions as a low-cost, familiar, locally delivered fibrinolytic that facilitates clot clearance or drainage. Supporting evidence remains heterogeneous and often derives from retrospective cohorts, small studies, and variable protocols. Recombinant human prourokinase should be distinguished pharmacologically and clinically from native urokinase. As a zymogen precursor preferentially activated at the fibrin-rich thrombus surface, it represents a renewed systemic reperfusion pathway. Following the historical proof of concept provided by PROACT II, PROST and PROST-2 showed intravenous recombinant human prourokinase to be non-inferior to alteplase for excellent 90-day functional outcomes; PROST-2 additionally reported lower rates of symptomatic intracranial hemorrhage and major bleeding. External generalizability and direct comparison with tenecteplase remain unresolved. The contemporary urokinase pathway therefore reflects a dual evolution: native urokinase retains focused local and access-driven roles, whereas recombinant prourokinase has re-entered systemic reperfusion therapy.

The interaction between coagulation factor Ⅴ (FⅤ) and tissue factor pathway inhibitor alpha (TFPIα) is a central regulator of hemostatic balance. The acidic region (AR2) of the FⅤ B domain interacts with either its basic region (BR) or the basic C-terminal tail of TFPIα, modulating FⅤ activity. Recent cryo-electron microscopy studies have resolved the high-resolution structures of FⅤ-short and full-length FⅤ, revealing that AR2 forms a negatively charged hydrophobic platform that mediates BR or TFPIα binding. These insights confirm the BR-AR2 interaction as crucial for maintaining FⅤ in its inactive state and clarify the molecular basis of FⅤ-related disorders, highlighting the FⅤ-TFPIα interface as a promising therapeutic target for bleeding and thrombotic diseases.

Reperfusion therapies improve outcomes in acute ischaemic stroke, but hyperacute treatment decisions remain complex and are rarely informed by individualised outcome predictions. Artificial intelligence (AI)-based clinical decision support systems (CDSS) could provide real-time prognostic estimates, yet prospective evidence of their feasibility and performance within routine workflows is scarce. We aim to prospectively evaluate the real-time feasibility, usability and predictive performance of an AI-based CDSS (VALIDATE-CDSS) for individualised outcome prediction in acute stroke care.

Timely vascular access is critical in neurological emergencies, where delays in treatment may worsen secondary brain injury and functional outcomes. Intraosseous access offers a rapid alternative when intravenous cannulation is difficult, delayed, or unsuccessful, but its role in neurocritical care remains incompletely defined. PubMed, ScienceDirect, and Scopus were searched from inception through August 2025, with a targeted evidence update through 10 September 2026. This critical narrative review examines the feasibility, pharmacologic considerations, safety, evidence quality, and research gaps surrounding intraosseous access across acute ischemic and hemorrhagic stroke, status epilepticus, traumatic brain injury, neurological infections, metabolic encephalopathy, pediatric neurological emergencies, and cardiac arrest as an indirect neurologic outcome model. Available evidence supports intraosseous access as a technically feasible emergency route in selected scenarios, particularly when vascular access delay may postpone time-sensitive therapy. However, most data are derived from case reports, animal pharmacokinetic studies, heterogeneous emergency cohorts, or extrapolation from resuscitation and trauma literature. Direct evidence demonstrating improved neurologic outcomes remains very limited and varies substantially by condition. Intravenous access should remain preferred when rapidly obtainable, while intraosseous access should be viewed as a temporary rescue bridge rather than a routine early intervention. Prospective condition-specific studies are needed to evaluate drug delivery, timing, insertion site, complications, workflow integration, and meaningful neurologic outcomes before neuro-focused intraosseous protocols can be broadly recommended.

The pathological mechanisms underlying cerebral ischemia-reperfusion injury (CIRI) are complex, and monotherapy with thrombolytic agents or pharmacological interventions alone has inherent limitations. We investigated the combined neuroprotective effects of hydroxysafflor yellow A (HSYA) and swimming exercise in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) injury. The MCAO/R model was established via the intraluminal suture method, with 2 h of ischemia followed by reperfusion. Rats were divided into sham, model, HSYA monotherapy, and HSYA combined with aerobic exercise groups. Water maze and open field tests revealed that the combination of HSYA combined with aerobic exercise significantly improved learning and memory abilities in MCAO/R rats. 2,3,5-Triphenyltetrazolium Chloride (TTC) staining showed that this combination significantly reduced cerebral infarct volume. HE and TUNEL staining further demonstrated that HSYA combined with aerobic exercise attenuated neuronal damage. Immunofluorescence and Western blot analyses consistently revealed that HSYA combined with aerobic exercise markedly upregulated the expression of tight junction proteins ZO-1 and occludin, indicating effective repair of the damaged blood-brain barrier (BBB). Moreover, it improved synaptic function, as evidenced by increased levels of PSD95, GAP43, and SYN, as well as neurotrophins including BDNF and NGF. Molecular docking and Western blot analysis further showed that HSYA combined with aerobic exercise significantly elevated the expression of HIF-1α and p-CREB. Collectively, these findings suggest that HSYA combined with aerobic exercise facilitates synaptic functional recovery via the HIF-1α/CREB pathway, providing novel experimental evidence and theoretical support for multimodal combinatorial therapeutic strategies against CIRI.