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Ischemic Stroke ll: Pathophysiology01:15

Ischemic Stroke ll: Pathophysiology

An ischemic stroke occurs when a cerebral blood vessel becomes obstructed, most often by a thrombus or embolus, interrupting the delivery of oxygen and glucose to brain tissue. Because neurons rely on continuous aerobic metabolism, energy failure begins within minutes of reduced perfusion. The region receiving the least blood flow becomes the infarct core, an area of irreversible cellular death. Surrounding this core lies the penumbra, a zone of hypoperfused but still viable tissue that is...

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Does inhibiting Sur1 complement rt-PA in cerebral ischemia?

J Marc Simard1, Zhihua Geng, Frank L Silver

  • 1Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland, USA. msimard@smail.umaryland.edu

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Glyburide may prevent hemorrhagic transformation after stroke treatment with recombinant tissue plasminogen activator (rt-PA). This drug inhibits MMP-9 activation, reducing stroke complications and improving outcomes in preclinical models.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Biochemistry

Background:

  • Hemorrhagic transformation (HT) is a complication of recombinant tissue plasminogen activator (rt-PA) treatment for stroke.
  • Matrix metalloproteinase 9 (MMP-9) plays a role in rt-PA-associated HT.
  • The sulfonylurea receptor 1 (Sur1) is implicated in stroke pathophysiology.

Purpose of the Study:

  • To review the role of MMP-9 in rt-PA-associated HT.
  • To explore the potential of glibenclamide (glyburide), a Sur1 inhibitor, in preventing rt-PA-associated HT.
  • To evaluate preclinical and clinical evidence for glyburide's protective effects.

Main Methods:

  • Review of existing literature on MMP-9 and rt-PA-induced HT.
  • Analysis of preclinical stroke models investigating glyburide's effects.
  • Examination of a retrospective clinical study on diabetic stroke patients treated with rt-PA and sulfonylureas.

Main Results:

  • Glyburide inhibits MMP-9 activation, reducing edema, swelling, and symptomatic HT.
  • Glyburide improves outcomes in preclinical stroke models, with or without rt-PA.
  • Diabetic patients on sulfonylureas maintained on rt-PA showed better outcomes.

Conclusions:

  • Inhibition of Sur1 with glyburide shows promise for mitigating rt-PA-associated HT.
  • Glyburide may offer a protective strategy against rt-PA-induced hemorrhagic complications in stroke.