Advances in Acute Ischemic Stroke Therapy

Circulation Research, Год журнала: 2022, Номер 130(8), С. 1230 - 1251

Опубликована: Апрель 14, 2022

The treatment of acute ischemic stroke continues to advance. mainstay remains intravenous thrombolysis with alteplase. Recent studies demonstrated that later alteplase is beneficial in patients selected advanced imaging techniques. Tenecteplase has been evaluated as an alternative thrombolytic drug and evidence suggests it least effective may lyse large vessel clots more effectively. Endovascular therapy mechanical thrombectomy now shown be up 24 hours after onset carefully proximal, occlusions. Ongoing are evaluating the effectiveness distal occlusions proximal larger core volumes also milder neurological deficits. Cytoprotection another potential not efficacy prior clinical trials. It should reconsidered adjunct reperfusion a variety new trials can envisioned evaluate benefits cytoprotection before reperfusion.

Язык: Английский

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Pharmacological brain cytoprotection in acute ischaemic stroke — renewed hope in the reperfusion era

Nature Reviews Neurology, Год журнала: 2022, Номер 18(4), С. 193 - 202

Опубликована: Янв. 25, 2022

Язык: Английский

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Most Promising Approaches to Improve Stroke Outcomes: The Stroke Treatment Academic Industry Roundtable XII Workshop

Stroke, Год журнала: 2023, Номер 54(12), С. 3202 - 3213

Опубликована: Окт. 27, 2023

The Stroke Treatment Academic Industry Roundtable XII included a workshop to discuss the most promising approaches improve outcome from acute stroke. brought together representatives academia, industry, and government representatives. discussion examined in 4 epochs: pre-reperfusion, reperfusion, post-reperfusion, access stroke interventions. participants identified areas of priority for developing new existing treatments outcomes. Although many advances therapy have been achieved, more work is necessary reperfusion therapies benefit possible patients. Prioritization should help guide use resources investigator efforts.

Язык: Английский

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Sublingual Edaravone Dexborneol for the Treatment of Acute Ischemic Stroke

JAMA Neurology, Год журнала: 2024, Номер 81(4), С. 319 - 319

Опубликована: Фев. 19, 2024

Sublingual edaravone dexborneol, which can rapidly diffuse and be absorbed through the oral mucosa after sublingual exposure, is a multitarget brain cytoprotection composed of antioxidant anti-inflammatory ingredients dexborneol.

Язык: Английский

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Metabolic Contribution and Cerebral Blood Flow Regulation by Astrocytes in the Neurovascular Unit

Cells, Год журнала: 2022, Номер 11(5), С. 813 - 813

Опубликована: Фев. 25, 2022

The neurovascular unit (NVU) is a conceptual framework that has been proposed to better explain the relationships between neural cells and blood vessels in human brain, focused mainly on brain gray matter. major components of NVU are neurons, astrocytes (astroglia), microvessels, pericytes, microglia. In addition, we believe oligodendrocytes should also be included as an indispensable component white Of all these components, particular have attracted interest researchers because their unique anatomical location; interposed neurons microvessels brain. Their location suggests might regulate cerebral flow (CBF) response neuronal activity, so ensure adequate supply glucose oxygen meet metabolic demands neurons. fact, adult which accounts for only 2% entire body weight, consumes approximately 20–25% total amount consumed by whole body. needs continuous essential energy sources through CBF, there practically no stores or brain; both acute chronic cessation CBF can adversely affect functions. another important putative function elimination heat waste materials produced activity. Recent evidence play pivotal roles not supplying glucose, but fatty acids amino Loss astrocytic support expected lead malfunction whole, underlies numerous neurological disorders. this review, shall focus historical recent findings with regard contributions NVU.

Язык: Английский

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Remote Ischemic Conditioning for Acute Stroke

JAMA, Год журнала: 2023, Номер 330(13), С. 1236 - 1236

Опубликована: Окт. 3, 2023

Importance Despite some promising preclinical and clinical data, it remains uncertain whether remote ischemic conditioning (RIC) with transient cycles of limb ischemia reperfusion is an effective treatment for acute stroke. Objective To evaluate the effect RIC when initiated in prehospital setting continued hospital on functional outcome patients Design, Setting, Participants This was a randomized trial conducted at 4 stroke centers Denmark that included 1500 symptoms less than hours (enrolled March 16, 2018, to November 11, 2022; final follow-up, February 3, 2023). Intervention The intervention delivered using inflatable cuff 1 upper extremity (RIC pressure, ≤200 mm Hg [n = 749] sham 20 751]). Each application consisted 5 minutes inflation followed by deflation. Treatment started ambulance repeated least once then twice daily 7 days among subset participants. Main Outcomes Measures primary end point improvement measured as shift across modified Rankin Scale (mRS) score (range, 0 [no symptoms] 6 [death]) 90 target population diagnosis or hemorrhagic Results Among who were (median age, 71 years; 591 women [41%]), 1433 (96%) completed trial. Of these, 149 (10%) diagnosed attack 382 (27%) mimic. In remaining 902 (737 [82%] 165 [18%] intracerebral hemorrhage), 436 underwent 466 treatment. median mRS 2 (IQR, 1-3) group group. not significantly associated improved (odds ratio [OR], 0.95; 95% CI, 0.75 1.20, P .67; absolute difference score, −1; −1.7 −0.25). all patients, there no significant differences number serious adverse events: 169 (23.7%) more events vs 175 (24.3%) (OR, 0.97; 0.85 1.11; .68). Upper pain during and/or skin petechia occurred 54 (7.2%) 11 (1.5%) Conclusions Relevance did improve Trial Registration ClinicalTrials.gov Identifier: NCT03481777

Язык: Английский

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A multi-laboratory preclinical trial in rodents to assess treatment candidates for acute ischemic stroke

Science Translational Medicine, Год журнала: 2023, Номер 15(714)

Опубликована: Сен. 20, 2023

Human diseases may be modeled in animals to allow preclinical assessment of putative new clinical interventions. Recent, highly publicized failures large trials called into question the rigor, design, and value assessment. We established Stroke Preclinical Assessment Network (SPAN) design implement a randomized, controlled, blinded, multi-laboratory trial for rigorous candidate stroke treatments combined with intravascular thrombectomy. Efficacy futility boundaries multi-arm multi-stage statistical aimed exclude from further study effective or futile interventions after each four sequential stages. Six independent research laboratories performed standard focal cerebral ischemic insult five animal models that included equal numbers males females: young mice, rats, aging mice diet-induced obesity, spontaneously hypertensive rats. The adhered common protocol efficiently enrolled 2615 full data completion comprehensive tracking. SPAN successfully implemented treatment masking, randomization, prerandomization inclusion exclusion criteria, blinded outcomes. infrastructure provide an approach could used similar preclinical, studies other disease areas should help improve reproducibility translational science.

Язык: Английский

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Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

JAMA, Год журнала: 2024, Номер 331(10), С. 840 - 840

Опубликована: Фев. 8, 2024

Importance It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective To assess the efficacy and adverse events of adjunctive low-dose thrombectomy secondary LVO. Design, Setting, Participants This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 proximal intracranial LVO presenting within 24 hours time last known be well. Recruitment took place between February 9, 2022, June 30, 2023, a final follow-up on September 2023. Interventions Eligible were randomly assigned (n = 839) 2 mg/kg/d or placebo 841) 3 days Main Outcomes Measures The primary outcome disability level 90 as measured by overall distribution modified Rankin Scale scores (range, 0 [no symptoms] 6 [death]). safety included mortality incidence symptomatic hemorrhage 48 hours. Results Among randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed trial. median 90-day score (IQR, 1-5) group vs 1-6) (adjusted generalized odds ratio lower disability, 1.10 [95% CI, 0.96-1.25]; P .17). In group, there rate (23.2% 28.5%; adjusted risk ratio, 0.84 0.71-0.98]; .03) (8.6% 11.7%; 0.74 0.55-0.99]; .04) compared placebo. Conclusions Relevance thrombectomy, added did not significantly improve degree disability. Trial Registration ChiCTR.org.cn Identifier: ChiCTR2100051729

Язык: Английский

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The Stroke Preclinical Assessment Network: Rationale, Design, Feasibility, and Stage 1 Results

Stroke, Год журнала: 2022, Номер 53(5), С. 1802 - 1812

Опубликована: Март 31, 2022

Cerebral ischemia and reperfusion initiate cellular events in brain that lead to neurological disability. Investigating these provides ample targets for developing new treatments. Despite considerable work, no such therapy has translated into successful stroke treatment. Among other issues—such as incomplete mechanistic knowledge faulty clinical trial design—a key contributor prior translational failures may be insufficient scientific rigor during preclinical assessment: nonblinded outcome assessment; missing randomization; inappropriate sample sizes; assessments young male animals ignore relevant biological variables, age, sex, comorbid diseases. Promising results are rarely replicated multiple laboratories. We sought address some of issues with rigorous assessment candidate treatments across 6 independent research The Stroke Preclinical Assessment Network (SPAN) implements state-of-the-art experimental design test the hypothesis can successfully reduce or eliminate common sources bias choosing evaluation studies. SPAN is a randomized, placebo-controlled, blinded, multilaboratory using multi-arm multi-stage protocol select one more putative an implied high likelihood success human trials. first stage implemented procedural standardization rigor. All participating laboratories performed middle cerebral artery occlusion surgery adhering rapidly enrolled 913 mice 4 planned stages excellent adherence, remarkable data completion low rates subject loss. 1 treatment masking, randomization, prerandomization inclusion/exclusion criteria, blinded exclude bias. Our suggest large, multilaboratory, effort known feasible practical. Subsequent will evaluate potential future trials aged conditions.

Язык: Английский

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Female-specific neuroprotection after ischemic stroke by vitronectin-focal adhesion kinase inhibition

Journal of Cerebral Blood Flow & Metabolism, Год журнала: 2022, Номер 42(10), С. 1961 - 1974

Опубликована: Июнь 14, 2022

We found that blood vitronectin (VTN) leaks into the brain and exacerbates tissue loss after stroke by increasing pro-inflammatory IL-6 expression in female, but not male, mice. VTN signals through integrins downstream focal adhesion kinase (FAK). Here, a two day systemic treatment with small molecule FAK inhibitor starting 6 h middle cerebral artery occlusion reduced ipsilateral injury size ∼40–45% at 7 14 d, as well inflammation motor dysfunction wild-type inhibition also injured female striatum 24 62%. Inducible selective gene deletion of astrocytes acute 72% only females, mitigated infarct ∼80% d stroke. Lastly, VTN−/− females had better outcomes, no additional protective or anti-inflammatory effects. Altogether, this suggests is detrimental primarily provides neuroprotection (cerebroprotection) reducing VTN-induced astrocytes. Thus, signaling can be targeted to mitigate harmful relevance treatments for women ischemic stroke, who often have worse outcomes than men.

Язык: Английский

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