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AIM2 inflammasome contributes to brain injury and chronic post-stroke cognitive impairment in mice.

Author information

Affiliations

  • 1. Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea; Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea; Graduate Training Program of Korean Medicine for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea.
      Authors
    • Kim H 1
    • Seo JS 1
    (2 authors)
  • 2. Department of Pharmacology, School of Medicine, Wonkwang University, Iksan, Jeonbuk 54538, Republic of Korea.
      Authors
    • Lee SY 2
    (1 author)
  • 3. Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea; Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea; Graduate Training Program of Korean Medicine for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea; Department of Korean Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea.
      Authors
    • Ha KT 3
    • Choi BT 3
    • Shin HK 3
    (3 authors)
  • 4. Department of Rehabilitation Medicine, School of Medicine, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea.
      Authors
    • Shin YI 4
    (1 author)
  • 5. Department of Korean Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea.
      Authors
    • Ju Yun Y 5
    (1 author)

ORCIDs linked to this article

Brain, Behavior, and Immunity, 19 Mar 2020, 87:765-776
https://doi.org/10.1016/j.bbi.2020.03.011 PMID: 32201254 

Abstract 

Although over one-third of stroke patients may develop post-stroke cognitive impairment (PSCI), the mechanisms underlying PSCI remain unclear. We explored here, the involvement of post-stroke inflammasomes in long-term PSCI development, using a 45 min-middle cerebral artery occlusion (MCAO)/reperfusion-induced PSCI model. Immunohistological assessment on day 1, 3, and 7 was followed by cognitive function test 28 days post-stroke. Evaluation of inflammasome sensor gene expression in aged mouse brains showed dominant expression of absent in melanoma 2 (Aim2) in 6-, 12-, and 18-month-old mouse brains. AIM2 mRNA and protein increased until 7 days post-stroke. PSCI decreased anxiety in elevated plus maze test and impaired spatial learning and memory functions in Morris water maze test 28 days post-stroke. AIM2 and other inflammasome subunit immunoreactivities, including those for caspase-1, interleukin (IL)-1β, and IL-18, were higher in the hippocampus and cortex of the PSCI than in those of the sham group 7 days post-stroke. AIM2 immunoreactivity of the PSCI group was primarily co-localized with Iba-1 (microglial marker) and CD31 (endothelial cell marker) immunoreactivities but not NeuN (neuronal marker) and GFAP (astrocyte marker) immunoreactivities, suggesting that microglia or endothelial cell-induced AIM2 production mediated PSCI pathogenesis. Additionally, inflammasome-induced pyroptosis might contribute to acute and chronic neuronal death after stroke. AIM2 knockout (KO) and Ac-YVAD-CMK-induced caspase-1 inhibition in mice significantly improved cognitive function and reversed brain volume in the hippocampus relative to those in stroke mice. Conclusively, AIM2 inflammasome-mediated inflammation and pyroptosis likely aggravated PSCI; therefore, targeting and controlling AIM2 inflammasome could potentially treat PSCI.

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Read article at publisher's site: https://doi.org/10.1016/j.bbi.2020.03.011

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Funding 

Funders who supported this work.

Ministry of Science, ICT and Future Planning (2)

National Research Foundation of Korea (2)