Vessel Dilation Attenuates Endothelial Dysfunction Following Middle Cerebral Artery Occlusion in Hyperglycemic Rats

CNS Neurosci Ther. 2016 Apr;22(4):316-24. doi: 10.1111/cns.12500. Epub 2016 Feb 4.

Abstract

Objectives: Dynamically observe cerebral vascular changes in hyperglycemic rats in vivo and explore the effect of diabetes on endothelial function after ischemic stroke.

Background: Diabetes affects both large and small vessels in the brain, but the dynamic process and mechanism are unclear.

Methods: We investigated the structural and functional changes of brain vasculature in living hyperglycemic rats and their impact on stroke outcomes via a novel technique: synchrotron radiation angiography. We also examined the effect of prolonged fasudil treatment on arterial reactivity and hemorrhagic transformation. Adult Sprague Dawley rats were treated by streptozotocin to induce type 1 diabetes. These hyperglycemic rats received fasudil pretreatment and then underwent transient middle cerebral artery occlusion.

Results: We found that diabetes caused arteries narrowing in the circus Willis as early as 2 weeks after streptozotocin injection (P < 0.05). These vessels were further constricted after middle cerebral artery occlusion. L-NAME could induce regional constrictions and impaired relaxation in hyperglycemic animals. Furthermore, hemorrhagic transformation was also increased in the hyperglycemic rats compared to the control (P < 0.05). In fasudil-treated rats, the internal carotid artery narrowing was ameliorated and L-NAME-induced regional constriction was abolished. Importantly, stroke prognosis was improved in fasudil-treated rats compared to the control (P < 0.05).

Conclusions: Our dynamic angiographic data demonstrated that diabetes could impair the cerebral arterial reactivity. Prolonged fasudil treatment could attenuate arterial dysfunction and improve the prognosis of ischemic stroke by affecting both the large and small vasculature.

Keywords: Fasudil; Hyperglycemia; Ischemia; Synchrotron radiation; Vascular dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives*
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • Animals
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Brain / pathology
  • Brain / physiopathology
  • Cerebral Angiography
  • Cerebral Arteries / diagnostic imaging
  • Cerebral Arteries / drug effects
  • Cerebral Arteries / pathology
  • Cerebral Arteries / physiopathology*
  • Cerebral Hemorrhage / drug therapy
  • Cerebral Hemorrhage / pathology
  • Cerebral Hemorrhage / physiopathology
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / physiopathology*
  • Endothelium, Vascular / diagnostic imaging
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / physiology
  • Hyperglycemia / pathology
  • Hyperglycemia / physiopathology*
  • Infarction, Middle Cerebral Artery / drug therapy
  • Infarction, Middle Cerebral Artery / pathology
  • Infarction, Middle Cerebral Artery / physiopathology*
  • NG-Nitroarginine Methyl Ester
  • Neuroprotective Agents / pharmacology
  • Organ Size
  • Rats, Sprague-Dawley
  • Vasodilator Agents / pharmacology*

Substances

  • Neuroprotective Agents
  • Vasodilator Agents
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • fasudil
  • NG-Nitroarginine Methyl Ester