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© 2022 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

Patients with vascular dementia, caused by cerebral ischemia, experience long-term cognitive impairment due to the lack of effective treatment. The mechanisms of and treatments for vascular dementia have been investigated in various animal models; however, the insufficient information on gene expression changes that define pathological conditions hampers progress. To investigate the underlying mechanism of and facilitate treatment development for vascular dementia, we established a mouse model of chronic cerebral hypoperfusion, including bilateral carotid artery stenosis, by using microcoils, and elucidated the molecular pathway underlying vascular dementia development. Rho-associated protein kinase (ROCK) 1/2, which regulates cellular structure, and inflammatory cytokines (IL-1 and IL-6) were upregulated in the vascular dementia model. However, expression of claudin-5, which maintains the blood–brain barrier, and MAP2 as a nerve cell-specific factor, was decreased in the hippocampal region of the vascular dementia model. Thus, we revealed that ROCK pathway activation loosens the tight junction of the blood–brain barrier and increases the influx of inflammatory cytokines into the hippocampal region, leading to neuronal death and causing cognitive and emotional dysfunction. Our vascular dementia model allows effective study of the vascular dementia mechanism. Moreover, the ROCK pathway may be a target for vascular dementia treatment development in the future.

Details

Title
Inflammation and Rho-Associated Protein Kinase-Induced Brain Changes in Vascular Dementia
Author
Eun Chae Lee 1 ; Dong-Yong, Hong 1   VIAFID ORCID Logo  ; Lee, Dong-Hun 1   VIAFID ORCID Logo  ; Park, Sang-Won 1   VIAFID ORCID Logo  ; Ji Young Lee 2 ; Jeong, Ji Hun 3 ; Eun-Young, Kim 4   VIAFID ORCID Logo  ; Hyung-Min, Chung 5 ; Ki-Sung, Hong 4 ; Park, Se-Pill 6 ; Lee, Man Ryul 3   VIAFID ORCID Logo  ; Oh, Jae Sang 1   VIAFID ORCID Logo 

 Department of Neurosurgery, College of Medicine, Cheonan Hospital, Soonchunhyang University, Cheonan 31151, Korea; [email protected] (E.C.L.); [email protected] (D.-Y.H.); [email protected] (D.-H.L.); [email protected] (S.-W.P.); [email protected] (J.Y.L.); Soonchunhyang Institute of Medi-Bio Science (SIMS), Soon Chun Hyang University, Cheonan 31151, Korea; [email protected] 
 Department of Neurosurgery, College of Medicine, Cheonan Hospital, Soonchunhyang University, Cheonan 31151, Korea; [email protected] (E.C.L.); [email protected] (D.-Y.H.); [email protected] (D.-H.L.); [email protected] (S.-W.P.); [email protected] (J.Y.L.) 
 Soonchunhyang Institute of Medi-Bio Science (SIMS), Soon Chun Hyang University, Cheonan 31151, Korea; [email protected] 
 Mireacellbio Co., Ltd., Seoul 04795, Korea; [email protected] (E.-Y.K.); [email protected] (H.-M.C.); [email protected] (K.-S.H.); [email protected] (S.-P.P.) 
 Mireacellbio Co., Ltd., Seoul 04795, Korea; [email protected] (E.-Y.K.); [email protected] (H.-M.C.); [email protected] (K.-S.H.); [email protected] (S.-P.P.); Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul 05029, Korea 
 Mireacellbio Co., Ltd., Seoul 04795, Korea; [email protected] (E.-Y.K.); [email protected] (H.-M.C.); [email protected] (K.-S.H.); [email protected] (S.-P.P.); Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, Jeju 63243, Korea 
First page
446
Publication year
2022
Publication date
2022
Publisher
MDPI AG
e-ISSN
22279059
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2632282858
Copyright
© 2022 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.