Inflammation and Rho-Associated Protein Kinase-Induced Brain Changes in Vascular Dementia
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 expres...
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MDPI AG
2022-02-01
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| Online Access: | https://www.mdpi.com/2227-9059/10/2/446 |
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| author | Eun Chae Lee Dong-Yong Hong Dong-Hun Lee Sang-Won Park Ji Young Lee Ji Hun Jeong Eun-Young Kim Hyung-Min Chung Ki-Sung Hong Se-Pill Park Man Ryul Lee Jae Sang Oh |
| author_facet | Eun Chae Lee Dong-Yong Hong Dong-Hun Lee Sang-Won Park Ji Young Lee Ji Hun Jeong Eun-Young Kim Hyung-Min Chung Ki-Sung Hong Se-Pill Park Man Ryul Lee Jae Sang Oh |
| author_sort | Eun Chae Lee |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T22:32:14Z |
| format | Article |
| id | doaj.art-c186c049457c40c0b8d4033a7846a934 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T22:32:14Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-c186c049457c40c0b8d4033a7846a9342023-11-23T18:55:43ZengMDPI AGBiomedicines2227-90592022-02-0110244610.3390/biomedicines10020446Inflammation and Rho-Associated Protein Kinase-Induced Brain Changes in Vascular DementiaEun Chae Lee0Dong-Yong Hong1Dong-Hun Lee2Sang-Won Park3Ji Young Lee4Ji Hun Jeong5Eun-Young Kim6Hyung-Min Chung7Ki-Sung Hong8Se-Pill Park9Man Ryul Lee10Jae Sang Oh11Department of Neurosurgery, College of Medicine, Cheonan Hospital, Soonchunhyang University, Cheonan 31151, KoreaDepartment of Neurosurgery, College of Medicine, Cheonan Hospital, Soonchunhyang University, Cheonan 31151, KoreaDepartment of Neurosurgery, College of Medicine, Cheonan Hospital, Soonchunhyang University, Cheonan 31151, KoreaDepartment of Neurosurgery, College of Medicine, Cheonan Hospital, Soonchunhyang University, Cheonan 31151, KoreaDepartment of Neurosurgery, College of Medicine, Cheonan Hospital, Soonchunhyang University, Cheonan 31151, KoreaSoonchunhyang Institute of Medi-Bio Science (SIMS), Soon Chun Hyang University, Cheonan 31151, KoreaMireacellbio Co., Ltd., Seoul 04795, KoreaMireacellbio Co., Ltd., Seoul 04795, KoreaMireacellbio Co., Ltd., Seoul 04795, KoreaMireacellbio Co., Ltd., Seoul 04795, KoreaSoonchunhyang Institute of Medi-Bio Science (SIMS), Soon Chun Hyang University, Cheonan 31151, KoreaDepartment of Neurosurgery, College of Medicine, Cheonan Hospital, Soonchunhyang University, Cheonan 31151, KoreaPatients 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.https://www.mdpi.com/2227-9059/10/2/446animal modelbehavior testbiomarkerblood–brain barriercognitive dysfunctioninflammation |
| spellingShingle | Eun Chae Lee Dong-Yong Hong Dong-Hun Lee Sang-Won Park Ji Young Lee Ji Hun Jeong Eun-Young Kim Hyung-Min Chung Ki-Sung Hong Se-Pill Park Man Ryul Lee Jae Sang Oh Inflammation and Rho-Associated Protein Kinase-Induced Brain Changes in Vascular Dementia Biomedicines animal model behavior test biomarker blood–brain barrier cognitive dysfunction inflammation |
| title | Inflammation and Rho-Associated Protein Kinase-Induced Brain Changes in Vascular Dementia |
| title_full | Inflammation and Rho-Associated Protein Kinase-Induced Brain Changes in Vascular Dementia |
| title_fullStr | Inflammation and Rho-Associated Protein Kinase-Induced Brain Changes in Vascular Dementia |
| title_full_unstemmed | Inflammation and Rho-Associated Protein Kinase-Induced Brain Changes in Vascular Dementia |
| title_short | Inflammation and Rho-Associated Protein Kinase-Induced Brain Changes in Vascular Dementia |
| title_sort | inflammation and rho associated protein kinase induced brain changes in vascular dementia |
| topic | animal model behavior test biomarker blood–brain barrier cognitive dysfunction inflammation |
| url | https://www.mdpi.com/2227-9059/10/2/446 |
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