TY - JOUR
T1 - Intermittent Lipopolysaccharide Exposure Significantly Increases Cortical Infarct Size and Impairs Autophagy
AU - Russell, Ashley E.
AU - Cavendish, John Z.
AU - Rai, Ali
AU - Vannoy, Mya
AU - Dakhlallah, Ahmad H.
AU - Hu, Heng
AU - Ren, Xuefang
AU - Amer, Amal
AU - Brown, Candice M.
AU - Marsh, Clay B.
AU - Simpkins, James W.
AU - Dakhlallah, Duaa
N1 - Publisher Copyright:
© The Author(s) 2021.
PY - 2021
Y1 - 2021
N2 - Globally, stroke is a leading cause of death and disability. Traditional risk factors like hypertension, diabetes, and obesity do not fully account for all stroke cases. Recent infection is regarded as changes in systemic immune signaling, which can increase thrombosis formation and other stroke risk factors. We have previously shown that administration of lipopolysaccharide (LPS) 30-minutes prior to stroke increases in infarct volume. In the current study, we found that animals intermittently exposed to LPS have larger cortical infarcts when compared to saline controls. To elucidate the mechanism behind this phenomenon, several avenues were investigated. We observed significant upregulation of tumor necrosis factor-alpha (TNF-α) mRNA, especially in the ipsilateral hemisphere of both saline and LPS exposed groups compared to sham surgery animals. We also observed significant reductions in expression of genes involved in autophagy in the ipsilateral hemisphere of LPS stroke animals. In addition, we assessed DNA methylation of autophagy genes and observed a significant increase in the ipsilateral hemisphere of LPS stroke animals. Intermittent exposure to LPS increases cortical infarct volume, downregulates autophagy genes, and induces hypermethylation of the corresponding CpG islands. These data suggest that intermittent immune activation may deregulate epigenetic mechanisms and promote neuropathological outcomes after stroke.
AB - Globally, stroke is a leading cause of death and disability. Traditional risk factors like hypertension, diabetes, and obesity do not fully account for all stroke cases. Recent infection is regarded as changes in systemic immune signaling, which can increase thrombosis formation and other stroke risk factors. We have previously shown that administration of lipopolysaccharide (LPS) 30-minutes prior to stroke increases in infarct volume. In the current study, we found that animals intermittently exposed to LPS have larger cortical infarcts when compared to saline controls. To elucidate the mechanism behind this phenomenon, several avenues were investigated. We observed significant upregulation of tumor necrosis factor-alpha (TNF-α) mRNA, especially in the ipsilateral hemisphere of both saline and LPS exposed groups compared to sham surgery animals. We also observed significant reductions in expression of genes involved in autophagy in the ipsilateral hemisphere of LPS stroke animals. In addition, we assessed DNA methylation of autophagy genes and observed a significant increase in the ipsilateral hemisphere of LPS stroke animals. Intermittent exposure to LPS increases cortical infarct volume, downregulates autophagy genes, and induces hypermethylation of the corresponding CpG islands. These data suggest that intermittent immune activation may deregulate epigenetic mechanisms and promote neuropathological outcomes after stroke.
UR - http://www.scopus.com/inward/record.url?scp=85101778202&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85101778202&partnerID=8YFLogxK
U2 - 10.1177/1759091421991769
DO - 10.1177/1759091421991769
M3 - Article
C2 - 33626880
AN - SCOPUS:85101778202
SN - 1759-0914
VL - 13
JO - ASN Neuro
JF - ASN Neuro
ER -