This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ashwal, S. Articles by Faraci, F. M. Search for Related Content PubMed PubMed Citation Articles by Ashwal, S. Articles by Faraci, F. M.

(Stroke. 1998;29:1037-1047.)
© 1998 American Heart Association, Inc.

Original Contributions

Core and Penumbral Nitric Oxide Synthase Activity During Cerebral Ischemia and Reperfusion

Stephen Ashwal, MD; Beatriz Tone, BA; Hui Rou Tian, MD; Daniel J. Cole, MD; William J. Pearce, PhD

From the Departments of Pediatrics (S.A., B.T.), Anesthesiology (H.R.T., D.J.C.), and Physiology, Division of Perinatal Biology (W.J.P.), Loma Linda University School of Medicine, Loma Linda, Calif.

Correspondence to Stephen Ashwal, MD, Department of Pediatrics, Loma Linda University School of Medicine, Coleman Pavillon, Loma Linda, CA 92354. E-mail Stephen_Ashwal{at}ccmail.llumc.edu

Background and Purpose—The present studies examined the hypothesis that the distribution of cerebral injury after a focal ischemic insult is associated with the regional distribution of nitric oxide synthase (NOS) activity.

Methods—Based on previous studies that certain anatomically well-defined areas are prone to become either core or penumbra after middle cerebral artery occlusion (MCAO), we measured NOS activity in these areas from the right and left hemispheres in a spontaneously hypertensive rat filament model. Four groups were studied: (1) controls (immediate decapitation); (2) 1.5 hours of MCAO with no reperfusion (R0); (3) 1.5 hours of MCAO with 0.5 hour of reperfusion (R0.5); and (4) 1.5 hours of MCAO with 24 hours of reperfusion (R24). Three groups of corresponding isoflurane sham controls were also included: 1.5 (S1.5) or 2 (S2.0) hours of anesthesia and 1.5 hours of anesthesia+24 hours of observation (S24).

Results—Control core NOS activity for combined right and left hemispheres was 129% greater than penumbral NOS activity (P<0.05). Combined core NOS activity was also greater (P<0.05) in the three sham groups: 208%, 122%, and 161%, respectively. In the three MCAO groups, ischemic and nonischemic core NOS remained higher than penumbral regions (P<0.05). However, NOS activity was lower in the ischemic than in the nonischemic core in all three groups: R0 (29% lower), R0.5 (48%), and R24 (86%) (P<0.05). Addition of cofactors (10 µmol/L tetrahydrobiopterin, 3 µmol/L flavin adenine dinucleotide, and 3 µmol/L flavin mononucleotide) increased NOS activity in all groups and lessened the decrease in ischemic core and penumbral NOS.

Conclusions—Greater NOS activity in core regions could explain in part the increased vulnerability of that region to ischemia and could theoretically contribute to the progression of the infarct over time. The data also suggest that NOS activity during ischemia and reperfusion could be influenced by the availability of cofactors.

Editorial Comment

Frank M. Faraci, PhD, Guest Editor

Department of Internal Medicine, Cardiovascular Division, University of Iowa College of Medicine, Iowa City, Iowa

This article has been cited by other articles:

				H. Hong, J.-S. Zeng, D. L. Kreulen, D. I. Kaufman, and A. F. Chen Atorvastatin protects against cerebral infarction via inhibition of NADPH oxidase-derived superoxide in ischemic stroke Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2210 - H2215. [Abstract] [Full Text] [PDF]

				C. M. Fitzpatrick, Y. Shi, W. C. Hutchins, J. Su, G. J. Gross, B. Ostadal, J. S. Tweddell, and J. E. Baker Cardioprotection in chronically hypoxic rabbits persists on exposure to normoxia: role of NOS and KATP channels Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H62 - H68. [Abstract] [Full Text] [PDF]

				Y. Shi, W. C. Hutchins, J. Su, D. Siker, N. Hogg, K. A. Pritchard Jr., A. Keszler, J. S. Tweddell, and J. E. Baker Delayed cardioprotection with isoflurane: role of reactive oxygen and nitrogen Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H175 - H184. [Abstract] [Full Text] [PDF]

				R. Veltkamp, N. Rajapakse, G. Robins, M. Puskar, K. Shimizu, and D. Busija Transient Focal Ischemia Increases Endothelial Nitric Oxide Synthase in Cerebral Blood Vessels Stroke, November 1, 2002; 33(11): 2704 - 2710. [Abstract] [Full Text] [PDF]

				R. S. Bonser, C. H. Wong, D. Harrington, D. Pagano, M. Wilkes, T. Clutton-Brock, and M. Faroqui Failure of retrograde cerebral perfusion to attenuate metabolic changes associated with hypothermic circulatory arrest J. Thorac. Cardiovasc. Surg., May 1, 2002; 123(5): 943 - 950. [Abstract] [Full Text] [PDF]

				J. Castillo, R. Rama, and A. Davalos Nitric Oxide-Related Brain Damage in Acute Ischemic Stroke Stroke, April 1, 2000; 31(4): 852 - 857. [Abstract] [Full Text] [PDF]

				M. Gbadegesin, S. Vicini, S. J. Hewett, D. A. Wink, M. Espey, R. M. Pluta, and C. A. Colton Hypoxia modulates nitric oxide-induced regulation of NMDA receptor currents and neuronal cell death Am J Physiol Cell Physiol, October 1, 1999; 277(4): C673 - C683. [Abstract] [Full Text] [PDF]