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Sample Preparation for Endopeptidomic Analysis in Human Cerebrospinal Fluid
Published on: December 4, 2017
Cerebrospinal fluid matrix-remodeling biomarkers in neonates with myelomeningocele: MMP-9, TIMP-1, and TGF-β1
Ibrahim Alataş1, Larisa Andrada Ay2, Hakkı Kemal Erdinç3
1Department of Neurosurgery, Spina Bifida and Fetal Center, İstanbul Beykent University, Istanbul, Turkey.
Purpose:
Matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of metalloproteinases, regulate extracellular matrix remodeling and neural tissue homeostasis. Transforming growth factor β1 modulates inflammation, ECM deposition, and tissue repair. Dysregulation of these pathways may contribute to congenital spinal dysraphism. This study quantified cerebrospinal fluid MMP-9, TIMP-1, and TGF-β1 in neonates with myelomeningocele and evaluated their potential as pathogenic mediators or biomarkers.
Methods:
Preoperative CSF samples were collected from 48 neonates with isolated myelomeningocele (Group 1) and 24 age-matched controls with sterile CSF (Group 2). MMP-9, TIMP-1, and TGF-β1 concentrations were measured via ELISA. Intergroup differences were analyzed, and Pearson correlation assessed relationships among biomarkers.
Results:
CSF MMP-9 levels were significantly elevated in neonates with myelomeningocele compared to controls (57.12 ± 64.19 ng/mL vs. 11.29 ± 6.79 ng/mL; p < 0.05). TIMP-1 (368.78 ± 220.08 ng/mL vs. 450.04 ± 390.22 ng/mL) and TGF-β1 (2.32 ± 1.44 ng/mL vs. 2.524 ± 1.07 ng/mL) did not differ significantly. MMP-9 correlated positively with TIMP-1 across all subjects (p < 0.05) and with TGF-β1 within the myelomeningocele group (p < 0.05), indicating coordinated regulation of ECM degradation and fibrogenic signaling.
Conclusion:
Elevated CSF MMP-9 in neonates with myelomeningocele suggests dysregulated ECM remodeling may be associated with neural tube malformation. MMP-9 may serve as a biomarker of ECM dysregulation, providing insights into the pathogenesis of congenital spinal dysraphism and identifying possible targets for future therapeutic interventions.
Insights
Elevated matrix metalloproteinase-9 (MMP-9) in cerebrospinal fluid of neonates with myelomeningocele suggests abnormal extracellular matrix remodeling contributes to neural tube defects. MMP-9 may serve as a biomarker for this condition.
Area of Science:
- Neuroscience
- Developmental Biology
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate extracellular matrix (ECM) remodeling and neural tissue homeostasis.
- Transforming growth factor β1 (TGF-β1) influences inflammation, ECM deposition, and tissue repair.
- Dysregulation of these pathways is implicated in congenital spinal dysraphism.
Purpose of the Study:
- To quantify cerebrospinal fluid (CSF) levels of MMP-9, TIMP-1, and TGF-β1 in neonates with myelomeningocele.
- To evaluate the potential of these molecules as pathogenic mediators or biomarkers in myelomeningocele.
Main Methods:
- Preoperative CSF samples were collected from 48 neonates with myelomeningocele and 24 age-matched controls.
- MMP-9, TIMP-1, and TGF-β1 concentrations were measured using ELISA.
- Intergroup differences and biomarker correlations were analyzed.
Main Results:
- CSF MMP-9 levels were significantly elevated in neonates with myelomeningocele compared to controls (57.12 ± 64.19 ng/mL vs. 11.29 ± 6.79 ng/mL; p < 0.05).
- TIMP-1 and TGF-β1 levels did not differ significantly between groups.
- MMP-9 showed positive correlations with TIMP-1 and TGF-β1, suggesting coordinated regulation.
Conclusions:
- Elevated CSF MMP-9 in neonates with myelomeningocele indicates dysregulated ECM remodeling associated with neural tube malformation.
- MMP-9 may function as a biomarker for ECM dysregulation in congenital spinal dysraphism.
- These findings offer insights into pathogenesis and potential therapeutic targets.
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