Tenecteplase is a genetically mutated variant of alteplase with superior pharmacodynamic and pharmacokinetic properties. However, its efficacy and safety in acute ischemic strokes are limited. Hence, we conducted a study to evaluate the efficacy and safety of tenecteplase compared with alteplase in acute ischemic stroke. Electronic databases were searched for randomized clinical trials (RCTs) comparing tenecteplase with alteplase in acute ischemic stroke patients eligible for thrombolysis. We evaluated various efficacy and safety outcomes using random-effects models for both pairwise and Bayesian network meta-analyses along with meta-regression analyses. We included 5 RCTs with a total of 1585 patients. Compared with alteplase, tenecteplase treatment was associated with significantly greater complete recanalization (odd ratio [OR] 2.01; 95% confidence interval [CI] 1.04-3.87; p = 0.04) and early neurological improvement (OR 1.43; 95% CI 1.01-2.03; p = 0.05). There were no differences between the two thrombolytics in terms of excellent recovery (modified Rankin Scale [mRS] 0-1; OR 1.17; 95% CI 0.95-1.44; p = 0.13), functional independence (mRS 0-2; OR 1.24; 95% CI 0.78-1.98), poor recovery (mRS 4-6; OR 0.78; 95% CI 0.49-1.25; p = 0.31), complete/partial recanalization (OR 1.51; 95% CI 0.70-3.26; p = 0.30), any intracerebral hemorrhage (OR 0.81; 95% CI 0.56-1.17; p = 0.26), symptomatic intracerebral hemorrhage (OR 0.98; 95% CI 0.52-1.83; p = 0.94), or mortality (OR 0.83; 95% CI 0.54-1.26; p = 0.38). In network meta-analysis, there were better efficacy and imaging-based outcomes with tenecteplase 0.25 mg/kg without increased risk of safety outcomes. Our results demonstrate that in acute ischemic stroke, thrombolysis with tenecteplase is at least as effective and safe as alteplase.

Stroke is a leading cause of death and disability and currently only has one FDA approved pharmacological treatment (tissue plasminogen activator), which is only administered to a fraction of stroke patients due to contraindications. New treatments are desperately needed but most treatments fail in clinical trials, even after showing benefit in animal models of stroke. To increase the translatability of animal stroke research to humans, sensitive functional measures for both the acute and chronic stages in animal models of stroke are needed. The objective of this study was to determine the sensitivity of certain behavioral tasks, up to seven weeks following occlusion of the middle cerebral artery (MCAo) in rats. A battery of behavioral tasks, including rotorod, cylinder, and limb-placement, was conducted weekly for seven weeks. Also, a behavioral flexibility operant task was introduced at the end of the study to measure cognitive deficits. All functional outcome measures showed significant differences between stroke and control groups, indicating that these tasks are sensitive enough to detect deficits in a long-term MCAo study in rats. This provides useful information for those trying to increase translatability in their own stroke research by providing long-term sensitive testing paradigms in a relevant stroke model.

Circadian rhythms can affect physical or mental activities as well as the time of stroke onset. The impact of circadian rhythms on acute ischemic stroke (AIS) patients treated by recombinant alteplase (rt-PA) is still incongruent. This study aims to consider whether the outcomes of thrombolysis differ depending on stroke onset time and rt-PA infusion time in patients with AIS. A total of 447 AIS patients, who underwent rt-PA intravenous infusion within 4.5 hours after stroke onset, were enrolled in this study consecutively from June 2010 through December 2016. All of the patients were grouped based on the stroke onset time and rt-PA infusion time into two exact 12-hour intervals as daytime (06:01-18:00) and nighttime (18:01-06:00) and further divided into four subgroups at 6-hour time intervals (00:01-06:00, 06:01-12:00, 12:01-18:00 and 18:01-24:00). Major neurological improvement at 1 hour, 24 hours and 7 days, 7-day mortality rate and 24-hour hemorrhage transformation was recorded. The results showed that a total of 295 patients (66.4%) appeared with AIS and 252 (56.4%) were treated during daytime. Higher NIHSS at admission was observed when stroke occurred in nighttime, especially during 00:01-06:00. Patients with stroke onset in nighttime especially during 18:01-24:00 had a significant shorter onset-door time and onset-needle time. No differences of the major neurological improvement at 1 hour, 24 hours and 7 days, 24-hour hemorrhagic transformation and 7-day fatality rate were found among either 12-hour time frames or 6-hour time frames according to the time of stroke onset or rt-PA infusion. In conclusion, there was no evidence to predict that circadian rhythms could influence the outcomes of AIS patients treated with rt-PA in China, although stroke onset during nighttime might aggravate neurological impairment before treatment. Further, multicenter and prospective clinical trials with larger number of subjects are still needed to draw more reliable conclusions.

Since complement activation in the subacute or chronic phase after stroke was recently shown to stimulate neural plasticity, we investigated how complement activation and complement inhibition in the acute phase after murine stroke interacts with subsequent rehabilitation therapy to modulate neuroinflammation and neural remodeling. We additionally investigated how complement and complement inhibition interacts with tissue plasminogen activator (tPA), the other standard of care therapy for stroke, and an FDA preclinical requirement for translation of an experimental stroke therapy. CR2fH, an injury site-targeted inhibitor of the alternative complement pathway, significantly reduced infarct volume, hemorrhagic transformation and mortality, and significantly improved long-term motor and cognitive performance when administered 1.5 or 24 hours after middle cerebral artery occlusion. CR2fH interrupted a post-stroke inflammatory process, and significantly reduced inflammatory cytokine release, microglial activation and astrocytosis. Rehabilitation alone showed mild anti-inflammatory effects, including reduced complement activation, but only improved cognitive recovery. CR2fH combined with rehabilitation significantly potentiated cognitive and motor recovery compared to either intervention alone, and was associated with higher growth factor release and enhanced rehabilitation-induced neuroblast migration and axonal remodeling. Similar outcomes were seen in adult, aged and female mice. Using a microembolic model, CR2fH administered in combination with acute tPA therapy improved overall survival and enhanced the neuroprotective effects of t-PA, extending the treatment window for tPA therapy. A human counterpart of CR2fH has been shown to be safe and nonimmunogenic in humans, and we demonstrated robust deposition of C3d, the CR2fH targeting epitope, in ischemic human brains after stroke.Significance statementComplement inhibition is a potential therapeutic approach for stroke, but it is not known how complement inhibition would interact with current standards of care. We show that following murine ischemic stroke, rehabilitation alone induced mild anti-inflammatory effects and improved cognitive, but not motor recovery. However, brain-targeted and specific inhibition of the alternative complement pathway when combined with rehabilitation significantly potentiated cognitive and motor recovery compared to either intervention alone, via mechanisms involving neuroregeneration and enhanced brain remodeling. Further, inhibiting the alternative pathway of complement significantly enhanced the neuroprotective effects of thrombolytic therapy and markedly expanded the therapeutic window for thrombolytic therapy.

Ischemic stroke is a major cause of death and disability globally, and its incidence is increasing. The only treatment approved by the US Food and Drug Administration for acute ischemic stroke is thrombolytic treatment with recombinant tissue plasminogen activator. As an alternative, therapeutic hypothermia has shown excellent potential in preclinical and small clinical studies, but it has largely failed in large clinical studies. This has led clinicians to explore the combination of therapeutic hypothermia with other neuroprotective strategies. This review examines preclinical and clinical progress towards developing highly effective combination therapy involving hypothermia for stroke patients.

Over the past 50 years, the Journal of Neuroscience Nursing (JNN) has grown from a neurosurgical focus to the broader neuroscience focus alongside the professional nursing organization that it supports. Stroke care in JNN focused on the surgical treatment and nursing care for cranial treatment of conditions such as cerebral aneurysm, carotid disease, arteriovenous malformation, and artery bypass procedures. As medical science has grown and new medications and treatment modalities have been successfully trialed, JNN has brought to its readership this information about recombinant tissue plasminogen activator, endovascular trials, and new assessment tools such as the National Institute of Health Stroke Scale. JNN is on the forefront of publishing nursing research in the areas of stroke caregiver needs and community education for rapid treatment of stroke and stroke risk reduction. The journal has been timely and informative in keeping neuroscience nurses on the forefront of the changing world of stroke nursing.

We analyzed the levels of circulating tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI)-1 in acute hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS). The levels of tPA commonly increased in both diseases, whereas PAI-1 correlated with disease severity in HCPS but not in HFRS.