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A Thrombotic Stroke Model Based On Transient Cerebral Hypoxia-ischemia
06:01

A Thrombotic Stroke Model Based On Transient Cerebral Hypoxia-ischemia

Published on: August 18, 2015

Association between tPA therapy and raised early matrix metalloproteinase-9 in acute stroke

M Ning1, K L Furie, W J Koroshetz

  • 1Stroke Service, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Neurology
|May 24, 2006
PubMed
Abstract

Insights

Tissue plasminogen activator (tPA) therapy increases matrix metalloproteinase-9 (MMP9) levels in acute ischemic stroke patients. Elevated MMP9 is linked to poorer outcomes and may impact hemorrhagic transformation risk.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Clinical Medicine

Background:

  • Matrix metalloproteinase-9 (MMP9) is implicated in acute ischemic stroke.
  • Tissue plasminogen activator (tPA) is known to up-regulate MMP9 in animal models.
  • Investigated plasma MMP9 and its inhibitor TIMP1 in human stroke patients receiving tPA.

Purpose of the Study:

  • To determine plasma MMP9 and TIMP1 levels in tPA-treated versus untreated ischemic stroke patients.
  • To assess the relationship between tPA therapy and MMP9/TIMP1 levels.
  • To correlate MMP9 levels with stroke severity and outcomes.

Main Methods:

  • Enrolled ischemic stroke patients within 8 hours of onset and nonstroke controls.
  • Collected blood samples at multiple time points (within 8 hours, 24 hours, days, weeks).
  • Quantified MMP9 and TIMP1 using ELISA and gel zymography.

Main Results:

  • Hyperacute MMP9 levels were significantly higher in tPA-treated patients (43 ng/mL) compared to untreated patients (28 ng/mL).
  • tPA therapy independently predicted higher MMP9 levels, even after adjusting for stroke severity and hemorrhagic transformation.
  • A trend towards lower hyperacute TIMP1 was observed in tPA-treated patients.
  • Elevated hyperacute MMP9 correlated with poor 3-month modified Rankin Scale outcomes (r=0.58, p=0.0005).

Conclusions:

  • tPA therapy is an independent predictor of elevated plasma MMP9 within 8 hours of human ischemic stroke.
  • MMP9 may mediate hemorrhagic transformation, suggesting potential for alternative thrombolytics or MMP9 inhibition to improve safety.
  • Findings highlight the complex role of MMP9 in acute stroke management.

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