A2 Vertaisarvioitu katsausartikkeli tieteellisessä lehdessä
Targeting vascular inflammation in ischemic stroke: Recent developments on novel immunomodulatory approaches
Tekijät: Shashank Shekhar, Mark W.Cunningham, Mallikarjuna R. Pabbidi, Shaoxun Wang, George W. Booz, Fan Fan
Kustantaja: ELSEVIER SCIENCE BV
Julkaisuvuosi: 2018
Journal: European Journal of Pharmacology
Tietokannassa oleva lehden nimi: EUROPEAN JOURNAL OF PHARMACOLOGY
Lehden akronyymi: EUR J PHARMACOL
Vuosikerta: 833
Aloitussivu: 531
Lopetussivu: 544
Sivujen määrä: 14
ISSN: 0014-2999
eISSN: 1879-0712
DOI: https://doi.org/10.1016/j.ejphar.2018.06.028
Tiivistelmä
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/gamma delta 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 proinflammatory state at all stages will hopefully help in developing novel immunomodulatory approaches to improve mortality and functional outcome of those inflicted with ischemic stroke.
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/gamma delta 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 proinflammatory 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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