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Soluble guanylate cyclase α1β1 limits stroke size and attenuates neurological injury

(2010) STROKE. 41(8). p.1815-1819
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Abstract
Background and Purpose-Nitric oxide mediates endothelium-dependent vasodilation, modulates cerebral blood flow, and determines stroke outcome. Nitric oxide signals in part by stimulating soluble guanylate cyclase (sGC) to synthesize cGMP. To study the role of sGC in stroke injury, we compared the outcome of cerebral ischemia and reperfusion in mice deficient in the alpha(1) subunit of sGC (sGC alpha(-/-)(1)) with that in wild-type mice. Methods-Blood pressure, cerebrovascular anatomy, and vasoreactivity of pressurized carotid arteries were compared in both mouse genotypes. Cerebral blood flow was measured before and during middle cerebral artery occlusion and reperfusion. We then assessed neurological deficit and infarct volume after 1 hour of occlusion and 23 hours of reperfusion and after 24 hours of occlusion. Results-Blood pressure and cerebrovascular anatomy were similar between genotypes. We found that vasodilation of carotid arteries in response to acetylcholine or sodium nitroprusside was diminished in sGC alpha(-/-)(1) compared with wild-type mice. Cerebral blood flow deficits did not differ between the genotypes during occlusion, but during reperfusion, cerebral blood flow was 45% less in sGC alpha(-/-)(1) mice. Infarct volumes and neurological deficits were similar after 24 hours of occlusion in both genotypes. After 1 hour of ischemia and 23 hours of reperfusion, infarct volumes were 2-fold larger and neurological deficits were worse in sGC alpha(-/-)(1) than in the wild-type mice. Conclusion-sGC alpha(1) deficiency impairs vascular reactivity to nitric oxide and is associated with incomplete reperfusion, larger infarct size, and worse neurological damage, suggesting that cGMP generated by sGC alpha(1)beta(1) is protective in ischemic stroke. (Stroke. 2010; 41: 1815-1819.)
Keywords
CEREBRAL-BLOOD-FLOW, NITRIC-OXIDE, SYSTEM, BRAIN, CGMP, MICE DEFICIENT, mouse models, gene knockout mice, cerebral ischemia

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Chicago
Atochin, Dimitriy N, Izumi Yuzawa, QiAn Li, Kristen M Rauwerdink, Rajeev Malhotra, JunLei Chang, Peter Brouckaert, et al. 2010. “Soluble Guanylate Cyclase Α1β1 Limits Stroke Size and Attenuates Neurological Injury.” Stroke 41 (8): 1815–1819.
APA
Atochin, D. N., Yuzawa, I., Li, Q., Rauwerdink, K. M., Malhotra, R., Chang, J., Brouckaert, P., et al. (2010). Soluble guanylate cyclase α1β1 limits stroke size and attenuates neurological injury. STROKE, 41(8), 1815–1819.
Vancouver
1.
Atochin DN, Yuzawa I, Li Q, Rauwerdink KM, Malhotra R, Chang J, et al. Soluble guanylate cyclase α1β1 limits stroke size and attenuates neurological injury. STROKE. 2010;41(8):1815–9.
MLA
Atochin, Dimitriy N, Izumi Yuzawa, QiAn Li, et al. “Soluble Guanylate Cyclase Α1β1 Limits Stroke Size and Attenuates Neurological Injury.” STROKE 41.8 (2010): 1815–1819. Print.
@article{1023121,
  abstract     = {Background and Purpose-Nitric oxide mediates endothelium-dependent vasodilation, modulates cerebral blood flow, and determines stroke outcome. Nitric oxide signals in part by stimulating soluble guanylate cyclase (sGC) to synthesize cGMP. To study the role of sGC in stroke injury, we compared the outcome of cerebral ischemia and reperfusion in mice deficient in the alpha(1) subunit of sGC (sGC alpha(-/-)(1)) with that in wild-type mice.
Methods-Blood pressure, cerebrovascular anatomy, and vasoreactivity of pressurized carotid arteries were compared in both mouse genotypes. Cerebral blood flow was measured before and during middle cerebral artery occlusion and reperfusion. We then assessed neurological deficit and infarct volume after 1 hour of occlusion and 23 hours of reperfusion and after 24 hours of occlusion.
Results-Blood pressure and cerebrovascular anatomy were similar between genotypes. We found that vasodilation of carotid arteries in response to acetylcholine or sodium nitroprusside was diminished in sGC alpha(-/-)(1) compared with wild-type mice. Cerebral blood flow deficits did not differ between the genotypes during occlusion, but during reperfusion, cerebral blood flow was 45\% less in sGC alpha(-/-)(1) mice. Infarct volumes and neurological deficits were similar after 24 hours of occlusion in both genotypes. After 1 hour of ischemia and 23 hours of reperfusion, infarct volumes were 2-fold larger and neurological deficits were worse in sGC alpha(-/-)(1) than in the wild-type mice.
Conclusion-sGC alpha(1) deficiency impairs vascular reactivity to nitric oxide and is associated with incomplete reperfusion, larger infarct size, and worse neurological damage, suggesting that cGMP generated by sGC alpha(1)beta(1) is protective in ischemic stroke. (Stroke. 2010; 41: 1815-1819.)},
  author       = {Atochin, Dimitriy N and Yuzawa, Izumi and Li, QiAn and Rauwerdink, Kristen M and Malhotra, Rajeev and Chang, JunLei and Brouckaert, Peter and Ayata, Cenk and Moskowitz, Michael A and Bloch, Kenneth D and Huang, Paul L and Buys, Emmanuel S},
  issn         = {0039-2499},
  journal      = {STROKE},
  keyword      = {CEREBRAL-BLOOD-FLOW,NITRIC-OXIDE,SYSTEM,BRAIN,CGMP,MICE DEFICIENT,mouse models,gene knockout mice,cerebral ischemia},
  language     = {eng},
  number       = {8},
  pages        = {1815--1819},
  title        = {Soluble guanylate cyclase \ensuremath{\alpha}1\ensuremath{\beta}1 limits stroke size and attenuates neurological injury},
  url          = {http://dx.doi.org/10.1161/STROKEAHA.109.577635},
  volume       = {41},
  year         = {2010},
}

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