Targets of vascular protection in acute ischemic stroke differ in type 2 diabetes

Aisha I. Kelly-Cobbs, Roshini Prakash, Weiguo Li, Bindu Pillai, Sherif Hafez, Maha Coucha, Maribeth H Johnson, Safia N. Ogbi, Susan C. Fagan, Adviye Ergul

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Hemorrhagic transformation is an important complication of acute ischemic stroke, particularly in diabetic patients receiving thrombolytic treatment with tissue plasminogen activator, the only approved drug for the treatment of acute ischemic stroke. The objective of the present study was to determine the effects of acute manipulation of potential targets for vascular protection [i.e., NF-κB, peroxynitrite, and matrix metalloproteinases (MMPs)] on vascular injury and functional outcome in a diabetic model of cerebral ischemia. Ischemia was induced by middle cerebral artery occlusion in control and type 2 diabetic Goto-Kakizaki rats. Treatment groups received a single dose of the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III), the nonspecific NF-κB inhibitor curcumin, or the broadspectrum MMP inhibitor minocycline at reperfusion. Poststroke infarct volume, edema, hemorrhage, neurological deficits, and MMP-9 activity were evaluated. All acute treatments reduced MMP-9 and hemorrhagic transformation in diabetic groups. In addition, acute curcumin and minocycline therapy reduced edema in these animals. Improved neurological function was observed in varying degrees with treatment, as indicated by beam-walk performance, modified Bederson scores, and grip strength; however, infarct size was similar to untreated diabetic animals. In control animals, all treatments reduced MMP-9 activity, yet bleeding was not improved. Neuroprotection was only conferred by curcumin and minocycline. Uncovering the underlying mechanisms contributing to the success of acute therapy in diabetes will advance tailored stroke therapies.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume304
Issue number6
DOIs
StatePublished - Jun 10 2013

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Type 2 Diabetes Mellitus
Blood Vessels
Stroke
Minocycline
Curcumin
Matrix Metalloproteinase 9
Peroxynitrous Acid
Therapeutics
Edema
Hemorrhage
Matrix Metalloproteinase Inhibitors
Vascular System Injuries
Middle Cerebral Artery Infarction
Hand Strength
Tissue Plasminogen Activator
Brain Ischemia
Matrix Metalloproteinases
Reperfusion
Ischemia
Iron

Keywords

  • 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III)
  • Curcumin
  • Minocycline
  • Nuclear factor- κB
  • Vascular protection

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Targets of vascular protection in acute ischemic stroke differ in type 2 diabetes. / Kelly-Cobbs, Aisha I.; Prakash, Roshini; Li, Weiguo; Pillai, Bindu; Hafez, Sherif; Coucha, Maha; Johnson, Maribeth H; Ogbi, Safia N.; Fagan, Susan C.; Ergul, Adviye.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 304, No. 6, 10.06.2013.

Research output: Contribution to journalArticle

Kelly-Cobbs, Aisha I. ; Prakash, Roshini ; Li, Weiguo ; Pillai, Bindu ; Hafez, Sherif ; Coucha, Maha ; Johnson, Maribeth H ; Ogbi, Safia N. ; Fagan, Susan C. ; Ergul, Adviye. / Targets of vascular protection in acute ischemic stroke differ in type 2 diabetes. In: American Journal of Physiology - Heart and Circulatory Physiology. 2013 ; Vol. 304, No. 6.
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