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

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

Publication date: Mar 19, 2020

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 tests and impaired spatial learning and memory functions in Morris water maze tests 28 days post-stroke. AIM2 and other inflammasome subunit immunoreactivities, including those for caspase-1, interleukin (IL)-1?, 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.

Kim, H., Seo, J.S., Lee, S.Y., Ha, K.T., Choi, B.T., Shin, Y.I., Ju Yun, Y., and Shin, H.K. AIM2 inflammasome contributes to brain injury and chronic post-stroke cognitive impairment in mice. 26208. 2020 Brain Behav Immun.

Concepts Keywords
Anxiety Inflammation
Astrocyte Post stroke
Brain Involvement post stroke
Brain Injury Branches of biology
Caspase 1 Caspases
Cognitive Programmed cell death
Cognitive Impairment Cell biology
Cortex Cytokines
Endothelial Inflammasome
Endothelial Cell AIM2
GFAP Pyroptosis
Hippocampus Stroke
IL 1 PSCI
Immunoreactivities Hippocampus
Immunoreactivity
Inflammasome
Inflammation
Interleukin
Knockout
Maze
Melanoma
Memory
Mice
Microglia
Middle Cerebral Artery
Morris Water Maze
MRNA
Occlusion
Pathogenesis
Pyroptosis
Reperfusion
Sensor
Spatial Learning
Stroke

Semantics

Type Source Name
disease MESH stroke
disease MESH cognitive impairment
disease MESH development
disease MESH middle cerebral artery occlusion
disease MESH melanoma
pathway KEGG Melanoma
disease MESH anxiety
drug DRUGBANK Water
disease MESH death
disease MESH inflammation

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