Biomolecules & Therapeutics

  • 제28권6호
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  • Pages.512-518
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  • 2020
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  • 1976-9148(pISSN)
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  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
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Inhibition of LPA5 Activity Provides Long-Term Neuroprotection in Mice with Brain Ischemic Stroke

  • 투고 : 2020.09.13
  • 심사 : 2020.09.22
  • 발행 : 2020.11.01
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초록

Stroke is a leading cause of long-term disability in ischemic survivors who are suffering from motor, cognitive, and memory impairment. Previously, we have reported suppressing LPA5 activity with its specific antagonist can attenuate acute brain injuries after ischemic stroke. However, it is unclear whether suppressing LPA5 activity can also attenuate chronic brain injuries after ischemic stroke. Here, we explored whether effects of LPA5 antagonist, TCLPA5, could persist a longer time after brain ischemic stroke using a mouse model challenged with tMCAO. TCLPA5 was administered to mice every day for 3 days, starting from the time immediately after reperfusion. TCLPA5 administration improved neurological function up to 21 days after tMCAO challenge. It also reduced brain tissue loss and cell apoptosis in mice at 21 days after tMCAO challenge. Such long-term neuroprotection of TCLPA5 was associated with enhanced neurogenesis and angiogenesis in post-ischemic brain, along with upregulated expression levels of vascular endothelial growth factor. Collectively, results of the current study indicates that suppressing LPA5 activity can provide long-term neuroprotection to mice with brain ischemic stroke.

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참고문헌

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  1. Receptor for Advanced Glycation End Products Is Involved in LPA5-Mediated Brain Damage after a Transient Ischemic Stroke vol.11, pp.2, 2020, https://doi.org/10.3390/life11020080
  2. Critical Roles of Lysophospholipid Receptors in Activation of Neuroglia and Their Neuroinflammatory Responses vol.22, pp.15, 2021, https://doi.org/10.3390/ijms22157864