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Is Matrix Metalloproteinase-9 Associated with Post-Stroke Cognitive Impairment or Dementia?
Jianhua Zhao1, Fangli Yang1, Xue Peng2
1Department 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.
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).
Insights
Elevated matrix metalloproteinase-9 (MMP-9) levels and specific MMP-9 genetic variations are linked to cognitive decline after ischemic stroke. These factors significantly increase the risk of post-stroke cognitive impairment or dementia (PSCID).
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Matrix metalloproteinase-9 (MMP-9) is crucial for synaptic plasticity, learning, and memory.
- The precise role of MMP-9 in post-stroke cognitive decline remains unclear.
- Investigating MMP-9 and its genetic variations in relation to post-stroke cognitive impairment or dementia (PSCID) is essential.
Purpose of the Study:
- To determine the association between MMP-9 levels and genetic polymorphism with PSCID.
- To identify risk factors contributing to cognitive impairment following ischemic stroke.
- To elucidate the impact of MMP-9 on cognitive function post-stroke.
Main Methods:
- Clinical data from 148 PSCID patients, 169 patients without cognitive impairment (NCI), and 150 normal controls (NC) were analyzed.
- MMP-9 rs3918242 polymorphisms were assessed using PCR-RFLP.
- Serum MMP-9 levels were quantified via ELISA.
Main Results:
- Serum MMP-9 levels were significantly higher in PSCID and NCI groups compared to NC, with PSCID showing the highest levels.
- Diabetes mellitus, hyperhomocysteinemia, and elevated serum MMP-9 were identified as key risk factors for cognitive impairment.
- MMP-9 rs3918242 polymorphisms (TC and CC genotypes) and specific combinations with comorbidities were associated with increased PSCID risk.
Conclusions:
- MMP-9 serum levels and MMP-9 rs3918242 genetic polymorphism play a significant role in the development of PSCID.
- Understanding these factors can aid in predicting and potentially mitigating cognitive decline after stroke.
- Further research into MMP-9's role may reveal therapeutic targets for post-stroke cognitive dysfunction.
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