Abstract
Diabetes increases the risk of as well as poor outcome after stroke. Matrix metalloprotease (MMP) activation disrupts blood-brain barrier integrity after cerebral ischemia. We have previously shown that type 2 diabetes promotes remodeling of middle cerebral arteries (MCA) characterized by increased media/lumen (M/L) ratio and MMP activity in an endothelin (ET)-1-dependent manner in the Goto-Kakizaki (GK) rat model. In the present study, we examined the effects of ET-1-mediated vascular remodeling on neurovascular damage following cerebral ischemic injury in GK rats 5 and 12 weeks after the onset of diabetes. The MCA structure, cerebral perfusion as well as infarct size, and hemorrhage were measured in control and diabetic rats subjected to transient MCA occlusion. M/L ratio was increased after 12 but not 5 weeks of diabetes. The baseline cerebral perfusion was lower and the infarct volume smaller in diabetic rats in both age groups. The incidence of hemorrhagic transformation was higher after 5 weeks of diabetes as compared to that after 12 weeks or in the control groups. These findings provide evidence that ET-1-mediated cerebrovascular remodeling does not worsen the neurovascular damage of ischemic brain injury in diabetes. It is possible that this early remodeling response is compensatory in nature to regulate vascular tone and integrity, especially when ischemia is layered on diabetic vascular disease.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 788-795 |
| Number of pages | 8 |
| Journal | Canadian Journal of Physiology and Pharmacology |
| Volume | 88 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 1 2010 |
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Keywords
- Cerebral ischemia
- Diabetes
- ET-1
- Goto-Kakizaki rats
- Remodeling
ASJC Scopus subject areas
- Physiology
- Pharmacology
- Physiology (medical)
Cite this
Endothelin-1-mediated cerebrovascular remodeling is not associated with increased ischemic brain injury in diabetes. / Li, Weiguo; Kelly-Cobbs, Aisha I.; Mezzetti, Erin M.; Fagan, Susan C.; Ergul, Adviye.
In: Canadian Journal of Physiology and Pharmacology, Vol. 88, No. 8, 01.08.2010, p. 788-795.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Endothelin-1-mediated cerebrovascular remodeling is not associated with increased ischemic brain injury in diabetes
AU - Li, Weiguo
AU - Kelly-Cobbs, Aisha I.
AU - Mezzetti, Erin M.
AU - Fagan, Susan C.
AU - Ergul, Adviye
PY - 2010/8/1
Y1 - 2010/8/1
N2 - Diabetes increases the risk of as well as poor outcome after stroke. Matrix metalloprotease (MMP) activation disrupts blood-brain barrier integrity after cerebral ischemia. We have previously shown that type 2 diabetes promotes remodeling of middle cerebral arteries (MCA) characterized by increased media/lumen (M/L) ratio and MMP activity in an endothelin (ET)-1-dependent manner in the Goto-Kakizaki (GK) rat model. In the present study, we examined the effects of ET-1-mediated vascular remodeling on neurovascular damage following cerebral ischemic injury in GK rats 5 and 12 weeks after the onset of diabetes. The MCA structure, cerebral perfusion as well as infarct size, and hemorrhage were measured in control and diabetic rats subjected to transient MCA occlusion. M/L ratio was increased after 12 but not 5 weeks of diabetes. The baseline cerebral perfusion was lower and the infarct volume smaller in diabetic rats in both age groups. The incidence of hemorrhagic transformation was higher after 5 weeks of diabetes as compared to that after 12 weeks or in the control groups. These findings provide evidence that ET-1-mediated cerebrovascular remodeling does not worsen the neurovascular damage of ischemic brain injury in diabetes. It is possible that this early remodeling response is compensatory in nature to regulate vascular tone and integrity, especially when ischemia is layered on diabetic vascular disease.
AB - Diabetes increases the risk of as well as poor outcome after stroke. Matrix metalloprotease (MMP) activation disrupts blood-brain barrier integrity after cerebral ischemia. We have previously shown that type 2 diabetes promotes remodeling of middle cerebral arteries (MCA) characterized by increased media/lumen (M/L) ratio and MMP activity in an endothelin (ET)-1-dependent manner in the Goto-Kakizaki (GK) rat model. In the present study, we examined the effects of ET-1-mediated vascular remodeling on neurovascular damage following cerebral ischemic injury in GK rats 5 and 12 weeks after the onset of diabetes. The MCA structure, cerebral perfusion as well as infarct size, and hemorrhage were measured in control and diabetic rats subjected to transient MCA occlusion. M/L ratio was increased after 12 but not 5 weeks of diabetes. The baseline cerebral perfusion was lower and the infarct volume smaller in diabetic rats in both age groups. The incidence of hemorrhagic transformation was higher after 5 weeks of diabetes as compared to that after 12 weeks or in the control groups. These findings provide evidence that ET-1-mediated cerebrovascular remodeling does not worsen the neurovascular damage of ischemic brain injury in diabetes. It is possible that this early remodeling response is compensatory in nature to regulate vascular tone and integrity, especially when ischemia is layered on diabetic vascular disease.
KW - Cerebral ischemia
KW - Diabetes
KW - ET-1
KW - Goto-Kakizaki rats
KW - Remodeling
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UR - http://www.scopus.com/inward/citedby.url?scp=78650184572&partnerID=8YFLogxK
U2 - 10.1139/Y10-040
DO - 10.1139/Y10-040
M3 - Article
C2 - 20725136
AN - SCOPUS:78650184572
VL - 88
SP - 788
EP - 795
JO - Canadian Journal of Physiology and Pharmacology
JF - Canadian Journal of Physiology and Pharmacology
SN - 0008-4212
IS - 8
ER -