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Plasma Matrix Metalloproteinases in Patients With Stroke During Intensive Rehabilitation Therapy

      Highlights

      • Matrix metalloproteinases are enzymes that participate in both injury and tissue repair after stroke.
      • The use of biomarkers could help to adjust individual rehabilitation programs.
      • Plasma matrix metalloproteinase-12 and matrix metalloproteinase-13 are associated with stroke severity and poor outcomes.
      • High levels of plasma matrix metalloproteinase-3 are found in patients with improved motor recovery.

      Abstract

      Objective

      To study plasma levels of matrix metalloproteinases (MMPs) as potential markers of recovery during intensive rehabilitation therapy (IRT) after stroke.

      Design

      Prospective and descriptive 3-month follow-up study.

      Setting

      Rehabilitation unit and research center.

      Participants

      Patients with first-ever ischemic stroke (n=15) enrolled to IRT (≥3h/d and 5d/wk) and healthy volunteers (n=15) (N=30).

      Interventions

      Not applicable.

      Main Outcome Measures

      The primary outcome was to measure plasma MMP3, MMP12, and MMP13 levels and evaluate potential associations with motor/functional scales using a battery of tests (National Institutes of Health Stroke Scale, modified Rankin scale, Barthel Index, Fugl-Meyer Assessment, Functional Ambulation Categories, Medical Research Council scale, Chedoke Arm and Hand Activity Inventory, and the 10-m walk test) before IRT and at 1- and 3-month follow-ups. The secondary outcome was to evaluate the use of these MMPs as biomarkers as predictors of patient's outcome.

      Results

      MMP levels remained stable during the study period and were similar to those in the healthy volunteer group. However, baseline MMP12 and MMP13 levels were strongly associated with stroke severity and were found to be elevated in those patients with the poorest outcomes. Interestingly, plasma MMP3 was independent of baseline stroke characteristics but was found to be increased in patients with better motor/functional recovery and in patients with larger improvements during rehabilitation.

      Conclusions

      MMPs might act as biologic markers of recovery during rehabilitation therapy related to their roles in both injury and tissue remodeling. Future confirmatory investigations in multicenter studies are warranted by our data.

      Keywords

      List of abbreviations:

      BI (Barthel Index), FAC (Functional Ambulation Categories), FMA (Fugl-Meyer Assessment), IRT (intensive rehabilitation therapy), MMP (matrix metalloproteinase), MRC (Medical Research Council), NIHSS (National Institutes of Health Stroke Scale)
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