Adjunctive Therapy Approaches for Ischemic Stroke: Innovations to Expand Time Window of Treatment

Knecht, Talia; Story, Jacob; Liu, Jeffrey; Davis, Willie; Borlongan, Cesar V.; Peña, Ike dela

doi:10.3390/ijms18122756

Cited by 46 publications

(33 citation statements)

References 73 publications

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“…; 2) enhancing vascularization or angiogenesis, e.g., coumarin derivative IMM-H004 and granulocyte-colony stimulating factors (G-CSF); 3) with antioxidant properties, e.g., vitamin C (ascorbic acid); and 4) increasing oxygen delivery, e.g., dodecafluropentane emulsion nanodroplets or normobaric oxygen. A summary of agents and their major inflammation-related targets that showed promise in preclinical studies as adjunct therapy with t-PA is presented in Table 1 [see also (Knecht et al, 2017; Pena et al, 2017)].…”

Section: Recently Identified Therapeutic Aims and Therapiesmentioning

confidence: 99%

Targeting vascular inflammation in ischemic stroke: Recent developments on novel immunomodulatory approaches

Shekhar

Cunningham

Pabbidi

et al. 2018

European Journal of Pharmacology

100

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Ischemic stroke is a devastating and debilitating medical condition with limited therapeutic options. However, accumulating evidence indicates a central role of inflammation in all aspects of stroke including its initiation, the progression of injury, and recovery or wound healing. A central target of inflammation is disruption of the blood brain barrier or neurovascular unit. Here we discuss recent developments in identifying potential molecular targets and immunomodulatory approaches to preserve or protect barrier function and limit infarct damage and functional impairment. These include blocking harmful inflammatory signaling in endothelial cells, microglia/macrophages, or Th17/γδ T cells with biologics, third generation epoxyeicosatrienoic acid (EET) analogs with extended half-life, and miRNA antagomirs. Complementary beneficial pathways may be enhanced by miRNA mimetics or hyperbaric oxygenation. These immunomodulatory approaches could be used to greatly expand the therapeutic window for thrombolytic treatment with tissue plasminogen activator (t-PA). Moreover, nanoparticle technology allows for the selective targeting of endothelial cells for delivery of DNA/RNA oligonucleotides and neuroprotective drugs. In addition, although likely detrimental to the progression of ischemic stroke by inducing inflammation, oxidative stress, and neuronal cell death, 20-HETE may also reduce susceptibility of onset of ischemic stroke by maintaining autoregulation of cerebral blood flow. Although the interaction between inflammation and stroke is multifaceted, a better understanding of the mechanisms behind the pro-inflammatory state at all stages will hopefully help in developing novel immunomodulatory approaches to improve mortality and functional outcome of those inflicted with ischemic stroke.

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Section: Recently Identified Therapeutic Aims and Therapiesmentioning

confidence: 99%

Targeting vascular inflammation in ischemic stroke: Recent developments on novel immunomodulatory approaches

Shekhar

Cunningham

Pabbidi

et al. 2018

European Journal of Pharmacology

100

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“…It has been reported as a potential Evidence-Based Complementary and Alternative Medicine preventive and therapeutic CCVD safety reagent based on some experiments [48,49]. In addition, palmitic acid [50] (DC � 6, CC � 0.0332, BC � 0.3779), eugenol [51] (DC � 5, CC � 0.0297, BC � 0.4305), coumarin [52,53] (DC � 5, CC � 0.0127, BC � 0.3757), and linoleic acid [54] (DC � 4, CC � 0.0181, BC � 0.4140) also play an important role in anti-CCVDs.…”

Section: Compound-target-disease Network and Analysis In This Work mentioning

confidence: 99%

A Systems Pharmacology Approach for Identifying the Multiple Mechanisms of Action for the Rougui‐Fuzi Herb Pair in the Treatment of Cardiocerebral Vascular Diseases

Liu

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Cardiocerebral vascular diseases (CCVDs) are the main reasons for high morbidity and mortality all over the world, including atherosclerosis, hypertension, myocardial infarction, stroke, and so on. Chinese herbs pair of the Cinnamomum cassia Presl (Chinese name, rougui) and the Aconitum carmichaelii Debx (Chinese name, fuzi) can be effective in CCVDs, which is recorded in the ancient classic book Shennong Bencao Jing, Mingyibielu and Thousand Golden Prescriptions. However, the active ingredients and the molecular mechanisms of rougui-fuzi in treatment of CCVDs are still unclear. This study was designed to apply a system pharmacology approach to reveal the molecular mechanisms of the rougui-fuzi anti-CCVDs. The 163 candidate compounds were retrieved from Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP). And 84 potential active compounds and the corresponding 42 targets were obtained from systematic model. The underlying mechanisms of the therapeutic effect for rougui-fuzi were investigated with gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Then, component-target-disease (C-T-D) and target-pathway (T-P) networks were constructed to further dissect the core pathways, potential targets, and active compounds in treatment of CCVDs for rougui-fuzi. We also constituted protein-protein in interaction (PPI) network by the reflect target protein of the crucial pathways against CCVDs. As a result, 21 key compounds, 8 key targets, and 3 key pathways were obtained for rougui-fuzi. Afterwards, molecular docking was performed to validate the reliability of the interactions between some compounds and their corresponding targets. Finally, UPLC-Q-Exactive-MSE and GC-MS/MS were analyzed to detect the active ingredients of rougui-fuzi. Our results may provide a new approach to clarify the molecular mechanisms of Chinese herb pair in treatment with CCVDs at a systematic level.

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“…No entanto, quando administrado além da janela terapêutica, ocorrem efeitos danosos resultantes do medicamento, como a transformação hemorrágica. Com isso há necessidade novas abordagens que reduzam os riscos e flexibilizem o manejo (24,25). O tratamento com minociclina parece apresentar eficácia na prevenção e na reversão de alterações comportamentais e parâmetros oxidativos em modelos experimentais de neuropatologias agudas em roedores, favorecendo o uso da droga com baixos efeitos colaterais (13).…”

Section: Medline (N=176)unclassified

Atividade Neuroprotetora Da Minociclina Na Isquemia Cerebral: Revisão Sistemática

Alencar¹,

Alencar²,

Lima³

2019

Infarma

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O acidente vascular cerebral é causado pela interrupção do fluxo sanguíneo cerebral, podendo ser de gênese isquêmica. Os subtipos são determinados conforme a origem, podendo ser: aterosclerose de grandes artérias, cardioembolismo, oclusão de pequenas artérias, de outras origens determinadas e de origem desconhecida. O tratamento farmacológico é o Ativador de Plasminogenio Tecidual, de estreita janela terapêutica. A minociclina é capaz de atravessar a barreira hematoencefálica, atuando na perda neuronal, sendo um potencial neuroprotetor de grande aplicabilidade e especificidade, bloqueando grupos celulares responsáveis pelo processo inflamatório e degenerativo. O objetivo foi realizar uma revisão sistemática de caráter qualitativo. As bases de dados consultadas foram: MEDLINE), PubMed e SciELO, com os descritores: minociclina/neuroproteção e minocycline/neuroprotection, Apenas sete estudos foram selecionados por meio do protocolo de pesquisa, publicados entre 2014 e 2018 e disponíveis na íntegra gratuitamente. Minociclina possui relação com a inibição de NF-κB nos neurônios, efeito antioxidante, antiapoptótico, melhora no dano tecidual, recuperação funcional em animais, envolvimento com MCP1P1 e correlação com fatores os fatores CREB, pCREB, e BDNF. É notável a capacidade de neuroproteção obtida por meio do tratamento com minociclina em modelos isquêmicos.

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Adjunctive Therapy Approaches for Ischemic Stroke: Innovations to Expand Time Window of Treatment

Cited by 46 publications

References 73 publications

Targeting vascular inflammation in ischemic stroke: Recent developments on novel immunomodulatory approaches

Targeting vascular inflammation in ischemic stroke: Recent developments on novel immunomodulatory approaches

A Systems Pharmacology Approach for Identifying the Multiple Mechanisms of Action for the Rougui‐Fuzi Herb Pair in the Treatment of Cardiocerebral Vascular Diseases

Atividade Neuroprotetora Da Minociclina Na Isquemia Cerebral: Revisão Sistemática

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