Adenoviral Gene Transfer of Nitric Oxide Synthase Increases Cerebral Blood Flow in Rats

Neurosurgery ◽  
2000 ◽  
Vol 47 (5) ◽  
pp. 1206-1215 ◽  
Author(s):  
Jürgen C. Lüders ◽  
Conrad C. Weihl ◽  
George Lin ◽  
Ghanashayam Ghadge ◽  
Marcus Stoodley ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Saline Solution ◽  
Physiological Saline ◽  
Enos Gene ◽  
Messenger Ribonucleic Acid ◽  
Physiological Saline Solution ◽  
Oxide Synthase ◽  
Replication Defective Adenovirus

Abstract OBJECTIVE Depletion of nitric oxide may play a role in the development of vasospasm after aneurysmal subarachnoid hemorrhage. Replenishment of nitric oxide might be a useful treatment for vasospasm. Using rats, we performed intracisternal injections of replication-defective adenovirus containing the endothelial nitric oxide synthase (eNOS) gene and determined the localization of and effect on cerebral blood flow of transgene expression. METHODS Rats underwent baseline measurement of cortical cerebral blood flow using laser Doppler flowmetry. Replication-defective adenovirus containing the Escherichia coliLacZ gene (Ad327β-Gal, n = 2/time point) or the bovine eNOS gene (AdCD8-NOS, n = 4/time point) or physiological saline solution was injected into the cisterna magna. Cerebral blood flow was measured 1, 2, 4, 7, or 14 days later, and the animals were killed. Expression of β-galactosidase activity from the LacZ gene was examined by histochemical staining and that of eNOS was examined by polymerase chain reaction assays of messenger ribonucleic acid. Brains were histopathologically examined for inflammation. RESULTS β-Galactosidase activity was observed throughout the leptomeninges and in some cells in the adventitia of small subarachnoid blood vessels in the Ad327β-Gal-injected rats. Messenger ribonucleic acid for eNOS was detected in the leptomeninges and brainstem 1 and 2 days after injection of AdCD8-NOS. Rats injected with Ad327β-Gal or physiological saline solution exhibited decreased cerebral blood flow beginning 2 days after virus injection and lasting up to 14 days after injection. Rats injected with AdCD8-NOS developed significant transient increases in cerebral blood flow 2 days after virus injection, followed by slight decreases in blood flow. There was inflammation in the subarachnoid space of all animals; the inflammation was qualitatively worse in animals injected with Ad327β-Gal, compared with rats injected with AdCD8-NOS or saline solution. CONCLUSION Intracisternal injection of replication-defective adenovirus containing the eNOS gene can transiently increase cerebral blood flow.

scholarly journals Rapid nontranscriptional activation of endothelial nitric oxide synthase mediates increased cerebral blood flow and stroke protection by corticosteroids

2003 ◽  
Vol 111 (5) ◽  
pp. 759-759
Author(s):  
Florian P. Limbourg ◽  
Zhihong Huang ◽  
Jean-Christophe Plumier ◽  
Tommaso Simoncini ◽  
Masayuki Fujioka ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

scholarly journals Rapamycin Induces an eNOS (Endothelial Nitric Oxide Synthase) Dependent Increase in Brain Collateral Perfusion in Wistar and Spontaneously Hypertensive Rats

Stroke ◽  
2020 ◽  
Vol 51 (9) ◽  
pp. 2834-2843
Author(s):  
Daniel J. Beard ◽  
Zhaojin Li ◽  
Anna M. Schneider ◽  
Yvonne Couch ◽  
Marilyn J. Cipolla ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Nitric Oxide Synthase ◽  
Spontaneously Hypertensive Rats ◽  
Infarct Volume ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Background and Purpose: Rapamycin is a clinically approved mammalian target of rapamycin inhibitor that has been shown to be neuroprotective in animal models of stroke. However, the mechanism of rapamycin-induced neuroprotection is still being explored. Our aims were to determine if rapamycin improved leptomeningeal collateral perfusion, to determine if this is through eNOS (endothelial nitric oxide synthase)-mediated vessel dilation and to determine if rapamycin increases immediate postreperfusion blood flow. Methods: Wistar and spontaneously hypertensive rats (≈14 weeks old, n=22 and n=15, respectively) were subjected to ischemia by middle cerebral artery occlusion (90 and 120 minutes, respectively) with or without treatment with rapamycin at 30-minute poststroke. Changes in middle cerebral artery and collateral perfusion territories were measured by dual-site laser Doppler. Reactivity to rapamycin was studied using isolated and pressurized leptomeningeal anastomoses. Brain injury was measured histologically or with triphenyltetrazolium chloride staining. Results: In Wistar rats, rapamycin increased collateral perfusion (43±17%), increased reperfusion cerebral blood flow (16±8%) and significantly reduced infarct volume (35±6 versus 63±8 mm 3 , P <0.05). Rapamycin dilated leptomeningeal anastomoses by 80±9%, which was abolished by nitric oxide synthase inhibition. In spontaneously hypertensive rats, rapamycin increased collateral perfusion by 32±25%, reperfusion cerebral blood flow by 44±16%, without reducing acute infarct volume 2 hours postreperfusion. Reperfusion cerebral blood flow was a stronger predictor of brain damage than collateral perfusion in both Wistar and spontaneously hypertensive rats. Conclusions: Rapamycin increased collateral perfusion and reperfusion cerebral blood flow in both Wistar and comorbid spontaneously hypertensive rats that appeared to be mediated by enhancing eNOS activation. These findings suggest that rapamycin may be an effective acute therapy for increasing collateral flow and as an adjunct therapy to thrombolysis or thrombectomy to improve reperfusion blood flow.

A255 HEAD INJURY AND NITRIC OXIDE SYNTHASE INHIBITION REDUCE CEREBRAL BLOOD FLOW EQUALLY IN RATS

1997 ◽  
Vol 87 (Supplement) ◽  
pp. 255A
Author(s):  
Douglas DeWitt ◽  
Larry W. Jenkins ◽  
Chris W. Tidwell ◽  
Donald S. Prough
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Head Injury ◽  
Nitric Oxide Synthase ◽  
Oxide Synthase

Effects of Nitric Oxide Synthase Inhibitors on Cerebral Blood Flow and Autoregulation in Rats

1992 ◽  
Vol 77 (Supplement) ◽  
pp. A689 ◽  
Author(s):  
D S DeWitt ◽  
D S Prough ◽  
D M Colonna ◽  
D D Deal ◽  
S M Vines
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Nitric Oxide Synthase ◽  
Nitric Oxide Synthase Inhibitors ◽  
Oxide Synthase

scholarly journals Endothelial Nitric Oxide Synthase-Dependent Cerebral Blood Flow Augmentation by L-Arginine After Chronic Statin Treatment

2000 ◽  
Vol 20 (4) ◽  
pp. 709-717 ◽  
Author(s):  
Masaru Yamada ◽  
Zhihong Huang ◽  
Turgay Dalkara ◽  
Matthias Endres ◽  
Ulrich Laufs ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Nitric Oxide Synthase ◽  
Laser Doppler Flowmetry ◽  
Brain Blood Flow ◽  
Arginine Infusion ◽  
Doppler Flowmetry ◽  
Ischemic Brain ◽  
Oxide Synthase

Nitric oxide, a product of nitric oxide synthase activity, relaxes vascular smooth muscle and elevates brain blood flow. We evaluated the importance of eNOS to cerebral blood flow augmentation after L-arginine infusion and increases in flow after eNOS upregulation in SV-129 mice. Blood flow was measured by laser-Doppler flowmetry before and after L-arginine infusion (450 mg/kg during a 15-minute period) or measured by 14C-iodoamphetamine indicator fractionation or 14C-iodoantipyrine tissue equilibration techniques. rCBF increased by 26% (laser Doppler flowmetry) after L-arginine infusion but did not change in mutant mice deficient in eNOS expression. After eNOS upregulation by chronic simvastatin treatment (2 mg/kg subcutaneously, daily for 14 days), L-arginine amplified and sustained the hyperemia (38%) and increased absolute brain blood flow from 86 ± 7 to 119 ± 10 mL/100 g per minute. Furthermore, pretreatment with simvastatin enhanced blood flow within ischemic brain tissue after middle cerebral artery occlusion. Together, these findings suggest that eNOS activity is critical for blood flow augmentation during acute L-arginine infusion, and chronic eNOS upregulation combined with L-arginine administration provides a novel strategy to elevate cerebral blood flow in the normal and ischemic brain.

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