Recycled Translation: Repurposing Drugs for Stroke

Spellicy, Samantha E.; Hess, David C.

doi:10.1007/s12975-022-01000-z

Cited by 7 publications

(4 citation statements)

References 65 publications

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“…Intravenous thrombolysis with recombinant human tissue plasminogen activator (rtPA) is the only effective treatment for vascular recanalization in patients with acute ischemic stroke. 4 However, patient response to rtPA thrombolysis remains highly variable, even with standardized assessment. Nearly 50% of patients still experience adverse clinical outcomes, such as failure to recanalize and hemorrhagic transformation after recanalization after rtPA exerts its thrombolytic biological effect, indicating the lack of effectiveness of recanalization.…”

Section: Introductionmentioning

confidence: 99%

“…While recent studies, including DAWN, 1 DEFUSE‐3, 2 and MR CLEAN‐LATE, 3 have shown advances in endovascular treatment using imaging modalities, effective treatments for ischemic stroke remain limited. Intravenous thrombolysis with recombinant human tissue plasminogen activator (rtPA) is the only effective treatment for vascular recanalization in patients with acute ischemic stroke 4 . However, patient response to rtPA thrombolysis remains highly variable, even with standardized assessment.…”

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Neutrophil migration participates in the side effect of recombinant human tissue plasminogen activator

Huang,

Han,

Shen

et al. 2024

CNS Neurosci Ther

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AimsIschemic stroke remains a challenge in medical research because of the limited treatment options. Recombinant human tissue plasminogen activator (rtPA) is the primary treatment for recanalization. However, nearly 50% of the patients experience complications that result in ineffective reperfusion. The precise factors contributing to ineffective reperfusion remain unclear; however, recent studies have suggested that immune cells, notably neutrophils, may influence the outcome of rtPA thrombolysis via mechanisms such as the formation of neutrophil extracellular traps. This study aimed to explore the nonthrombolytic effects of rtPA on neutrophils and highlight their contribution to ineffective reperfusion.MethodsWe evaluated the effects of rtPA treatment on middle cerebral artery occlusion in rats. We also assessed neutrophil infiltration and activation after rtPA treatment in vitro and in vivo in a small cohort of patients with massive cerebral ischemia (MCI).ResultsrtPA increased neutrophil infiltration into the brain microvessels and worsened blood–brain barrier damage during ischemia. It also increased the neutrophil counts of the patients with MCI.ConclusionNeutrophils play a crucial role in promoting ischemic injury and blood–brain barrier disruption, making them potential therapeutic targets.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neutrophil migration participates in the side effect of recombinant human tissue plasminogen activator

Huang,

Han,

Shen

et al. 2024

CNS Neurosci Ther

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“…Recombinant tissue plasminogen activator is the only clinical treatment approved by the United States Food and Drug Administration for stroke. However, the short half-time and extremely narrow therapeutic time window restrict its clinic application [1]. Although several promising drugs have been identified in preclinical studies, no neuroprotective molecule has been reported to show clinical efficacy in human trials [2,3].…”

Section: Introductionmentioning

confidence: 99%

Oleoylethanolamide Protects against Acute Ischemic Stroke by Promoting PPARα-Mediated Microglia/Macrophage M2 Polarization

Liu¹,

Zhang²,

Wang³

et al. 2023

Pharmaceuticals

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Oleoylethanolamide (OEA) has been demonstrated to be a feasible protectant in ischemic stroke. However, the mechanism for OEA-afforded neuroprotection remains elusive. The present study aimed to investigate the neuroprotective effects of OEA on peroxisome proliferator-activated receptor α (PPARα)-mediated microglia M2 polarization after cerebral ischemia. Transient middle cerebral artery occlusion (tMCAO) was induced for 1 h in wild-type (WT) or PPARα-knock-out (KO) mice. Mouse small glioma cells (BV2) microglia and primary microglia cultures were used to evaluate the direct effect of OEA on microglia. A coculture system was used to further elucidate the effect of OEA on microglial polarization and ischemic neurons’ fate. OEA promoted the microglia switch from an inflammatory M1 phenotype to the protective M2 phenotype and enhanced the binding of PPARα with the arginase1 (Arg1) and Ym1 promoter in WT mice but not in KO mice after MCAO. Notably, the increased M2 microglia caused by OEA treatment were strongly linked to neuron survival after ischemic stroke. In vitro studies confirmed that OEA shifted BV2 microglia from (lipopolysaccharide) LPS-induced M1-like to M2-like phenotype through PPARα. Additionally, the activation of PPARα in primary microglia by OEA led to an M2 protective phenotype that enhanced neuronal survival against oxygen-glucose deprivation (OGD) in the coculture systems. Our findings demonstrate the novel effects of OEA in enhancing microglia M2 polarization to protect neighboring neurons by activating the PPARα signal, which is a new mechanism of OEA against cerebral ischemic injury. Therefore, OEA might be a promising therapeutic drug for stroke and targeting PPARα-mediated M2 microglia may represent a new strategy to treat ischemic stroke.

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Platelet membrane-functionalized hollow mesoporous Prussian blue nanomedicine for comprehensive thrombolytic management by targeted enhanced fibrinolysis and ROS scavenging

Zhang,

Sun,

Liu

et al. 2023

Chemical Engineering Journal

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Recycled Translation: Repurposing Drugs for Stroke

Cited by 7 publications

References 65 publications

Neutrophil migration participates in the side effect of recombinant human tissue plasminogen activator

Neutrophil migration participates in the side effect of recombinant human tissue plasminogen activator

Oleoylethanolamide Protects against Acute Ischemic Stroke by Promoting PPARα-Mediated Microglia/Macrophage M2 Polarization

Platelet membrane-functionalized hollow mesoporous Prussian blue nanomedicine for comprehensive thrombolytic management by targeted enhanced fibrinolysis and ROS scavenging

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