IMR Press / JIN / Volume 21 / Issue 6 / DOI: 10.31083/j.jin2106160
Open Access Original Research
Is Matrix Metalloproteinase-9 Associated with Post-Stroke Cognitive Impairment or Dementia?
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1 Department of Neurology, First Affiliated Hospital of Xinxiang Medical University, Henan Joint International Research Laboratory of Neurorestoratology for Senile Dementia, Henan Key Laboratory of Neurorestoratology, 453100 Xinxiang, Henan, China
2 Department of Neurology, the Sixth Hospital of Wuhan, Affiliated Hospital to Jianghan University, 430015 Wuhan, Hubei, China
3 Department of Medical Record Management, First Affiliated Hospital of Xinxiang Medical University, 453100 Xinxiang, Henan, China
4 Department of Imaging, First Affiliated Hospital of Xinxiang Medical University, 453100 Xinxiang, Henan, China
5 Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
*Correspondence: 051092@xxmu.edu.cn (Jianhua Zhao)
These authors contributed equally.
Academic Editors: Emilia Salvadori and Hahn Young Kim
J. Integr. Neurosci. 2022, 21(6), 160; https://doi.org/10.31083/j.jin2106160
Submitted: 10 June 2022 | Revised: 2 August 2022 | Accepted: 2 August 2022 | Published: 22 September 2022
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: Matrix metalloproteinase-9 (MMP-9) is a significant protease required for synaptic plasticity, learning, and memory. Yet, the role of MMP-9 in the occurrence and development of cognitive decline after ischemic stroke is not fully understood. In this study, we used clinical data experiments to further investigate whether MMP-9 and genetic polymorphism are associated with post-stroke cognitive impairment or dementia (PSCID). Materials and Methods: A total of 148 patients with PSCID confirmed by the Montreal Cognitive Assessment (MoCA) 3 months after onset (PSCID group) were included in the study. The MMP-9 rs3918242 polymorphisms were analyzed using polymerase chain reaction coupled with restriction fragment length polymorphism, and the serum level of MMP-9 was measured using enzyme-linked immunosorbent assay (ELISA). The same manipulations have been done on 169 ischemic stroke patients without cognitive impairment (NCI group) and 150 normal controls (NC group). Results: The expression level of serum MMP-9 in the PSCID group and NCI group was higher compared to the NC group, and the levels in the PSCID group were higher than that in the NCI group (all p < 0.05). Diabetes mellitus, hyperhomocysteinemia, and increased serum MMP-9 levels were the main risk factors of cognitive impairment after ischemic stroke. The serum level of MMP-9 was negatively correlated with the MoCA score, including visual-spatial executive, naming, attention, language, and delayed recall. Genetic polymorphism showed that TC genotype with MMP-9 rs3918242 and CC genotype were associated with a significantly increased risk of PSCID; moreover, the TC genotype significantly increased the risk of cognitive impairment. In the TCCC genotype of MMP-9 rs3918242, diabetes mellitus and hyperhomocysteinemia were associated with the increased risk of PSCID; also, hyperhomocysteinemia could increase the risk of cognitive impairment. Conclusions: MMP-9 level and MMP-9 rs3918242 polymorphism have an important role in the occurrence and development of post-stroke cognitive impairment or dementia (PSCID).

Keywords
ischemic stroke
post-stroke cognitive impairment or dementia (PSCID)
matrix metalloprotenase 9
genetic polymorphism
cognitive function
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Fig. 1.
Funding
182300410389/ Natural Science Foundation of Henan Province
LHGJ20190437/ Joint construction project of Henan Medical Science and technology research plan
YJSCX202185Y/ Xinxiang Medical University Scientific Research Innovation Support Program Project
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