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© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

We hypothesize that endothelial-specific thioredoxin-interacting protein knock-out (EC-TXNIP KO) mice will be more resistant to the neurovascular damage (hemorrhagic-transformation-HT) associated with hyperglycemia (HG) in embolic stroke. Adult-male EC-TXNIP KO and wild-type (WT) littermate mice were injected with-streptozotocin (40 mg/kg, i.p.) for five consecutive days to induce diabetes. Four-weeks after confirming HG, mice were subjected to embolic middle cerebral artery occlusion (eMCAO) followed by tissue plasminogen activator (tPA)-reperfusion (10 mg/kg at 3 h post-eMCAO). After the neurological assessment, animals were sacrificed at 24 h for neurovascular stroke outcomes. There were no differences in cerebrovascular anatomy between the strains. Infarct size, edema, and HT as indicated by hemoglobin (Hb)-the content was significantly higher in HG-WT mice, with or without tPA-reperfusion, compared to normoglycemic WT mice. Hyperglycemic EC-TXNIP KO mice treated with tPA tended to show lower Hb-content, edema, infarct area, and less hemorrhagic score compared to WT hyperglycemic mice. EC-TXNIP KO mice showed decreased expression of inflammatory mediators, apoptosis-associated proteins, and nitrotyrosine levels. Further, vascular endothelial growth factor-A and matrix-metalloproteinases (MMP-9/MMP-3), which degrade junction proteins and increase blood-brain-barrier permeability, were decreased in EC-TXNIP KO mice. Together, these findings suggest that vascular-TXNIP could be a novel therapeutic target for neurovascular damage after stroke.

Details

Title
Endothelial Thioredoxin-Interacting Protein Depletion Reduces Hemorrhagic Transformation in Hyperglycemic Mice after Embolic Stroke and Thrombolytic Therapy
Author
Salman, Mohd 1   VIAFID ORCID Logo  ; Saifudeen Ismael 1   VIAFID ORCID Logo  ; Li, Lexiao 1 ; Ahmed, Heba A 1 ; Puchowicz, Michelle A 2 ; Tauheed Ishrat 3 

 Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, TN 38163, USA; [email protected] (M.S.); [email protected] (S.I.); [email protected] (L.L.); [email protected] (H.A.A.) 
 Department of Pediatrics, The University of Tennessee Health Science Center, Memphis, TN 38163, USA; [email protected] 
 Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, TN 38163, USA; [email protected] (M.S.); [email protected] (S.I.); [email protected] (L.L.); [email protected] (H.A.A.); Department of Pharmaceutical Sciences, The University of Tennessee Health Science Center, Memphis, TN 38163, USA; Neuroscience Institute, University of Tennessee Health Science Center, Memphis, TN 38163, USA 
First page
983
Publication year
2021
Publication date
2021
Publisher
MDPI AG
e-ISSN
14248247
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2584463508
Copyright
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.