QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (48) Citing Articles via Google Scholar Google Scholar Articles by Han, H. S. Articles by Yenari, M. A. Search for Related Content PubMed PubMed Citation Articles by Han, H. S. Articles by Yenari, M. A.

 Previous Article  |  Next Article 

The Journal of Neuroscience, May 15, 2002, 22(10):3921-3928

Influence of Mild Hypothermia on Inducible Nitric Oxide Synthase Expression and Reactive Nitrogen Production in Experimental Stroke and Inflammation

Hyung Soo Han^{1, 2}, Yanli Qiao^{1, 3}, Murat Karabiyikoglu², Rona G. Giffard³, and Midori A. Yenari^{1, 2}

Departments of ¹ Neurology, ² Neurosurgery, and ³ Anesthesia, Stanford University Medical Center, Stanford, California 94305

Mild hypothermia is neuroprotective, but the reasons are not well known. Inflammation contributes to ischemic damage; therefore, we examined whether the protection by hypothermia may be attributable to alterations in the inflammation. We examined whether hypothermia might alter the inflammatory cell-associated inducible nitric oxide synthase (iNOS) and subsequent nitric oxide (NO) and peroxynitrite generation in experimental stroke and inflammation. Rats underwent 2 hr of middle cerebral artery occlusion (MCAO). Brain inflammation was modeled by intravenous lipopolysaccharide (LPS) (2 mg/kg) injection. Temperature was maintained at 33°C for 2 hr immediately after MCAO and LPS injection, delayed 2 hr after MCAO or maintained at 38°C. Cultured microglia were activated with LPS and then incubated at 33 or 37°C. Both intraischemic and delayed mild hypothermia attenuated infarct size by 40% (p < 0.05). Immunohistochemistry was performed to identify cell type, iNOS, and peroxynitrite. The majority of iNOS- and peroxynitrite-positive cells were activated microglia-macrophages, and mild hypothermia significantly decreased the numbers of immunoreactive cells at 72 hr by >50% (p < 0.05). After ischemia, mild hypothermia decreased NO production by 40%. Similarly, hypothermia attenuated NO and iNOS in LPS-injected rats, as well as in cultured microglia. Aminoguanidine, an iNOS inhibitor, also attenuated infarct size and NO in ischemic and inflammation models. We conclude that mild hypothermia significantly inhibits the inflammatory response by affecting microglial iNOS-NO generation. Therapies directed against microglia or their activation may be useful in treating stroke.

Key words: focal cerebral ischemia; mild hypothermia; inducible nitric oxide synthase; microglia; peroxynitrite; lipopolysaccharide; inflammation

---

Copyright © 2002 Society for Neuroscience  0270-6474/02/22103921-08$05.00/0

This article has been cited by other articles:

				K. Liu, S. Mori, H. K. Takahashi, Y. Tomono, H. Wake, T. Kanke, Y. Sato, N. Hiraga, N. Adachi, T. Yoshino, et al. Anti-high mobility group box 1 monoclonal antibody ameliorates brain infarction induced by transient ischemia in rats FASEB J, December 1, 2007; 21(14): 3904 - 3916. [Abstract] [Full Text] [PDF]

				L. Sunday, M. M. Tran, D. N. Krause, and S. P. Duckles Estrogen and progestagens differentially modulate vascular proinflammatory factors Am J Physiol Endocrinol Metab, August 1, 2006; 291(2): E261 - E267. [Abstract] [Full Text] [PDF]

				L. Zhang, S. Kumar, A. Kaminski, C. Kasch, C. Sponholz, C. Stamm, Y. Ladilov, and G. Steinhoff Importance of endothelial nitric oxide synthase for the hypothermic protection of lungs against ischemia-reperfusion injury J. Thorac. Cardiovasc. Surg., May 1, 2006; 131(5): 969 - 974. [Abstract] [Full Text] [PDF]

				M. A. Yenari, L. Xu, X. N. Tang, Y. Qiao, and R. G. Giffard Microglia Potentiate Damage to Blood-Brain Barrier Constituents: Improvement by Minocycline In Vivo and In Vitro Stroke, April 1, 2006; 37(4): 1087 - 1093. [Abstract] [Full Text] [PDF]

				Y. L. Ma, X. Zhu, P. M. Rivera, O. Toien, B. M. Barnes, J. C. LaManna, M. A. Smith, and K. L. Drew Absence of cellular stress in brain after hypoxia induced by arousal from hibernation in Arctic ground squirrels Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2005; 289(5): R1297 - R1306. [Abstract] [Full Text] [PDF]

				A. Razmara, D. N. Krause, and S. P. Duckles Testosterone augments endotoxin-mediated cerebrovascular inflammation in male rats Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H1843 - H1850. [Abstract] [Full Text] [PDF]

				D. S. Warner, H. Sheng, and I. Batinic-Haberle Oxidants, antioxidants and the ischemic brain J. Exp. Biol., August 15, 2004; 207(18): 3221 - 3231. [Abstract] [Full Text] [PDF]

				M. Komine-Kobayashi, N. Chou, H. Mochizuki, A. Nakao, Y. Mizuno, and T. Urabe Dual Role of Fc{gamma} Receptor in Transient Focal Cerebral Ischemia in Mice Stroke, April 1, 2004; 35(4): 958 - 963. [Abstract] [Full Text] [PDF]

				H. Zhao, M. A. Yenari, R. M. Sapolsky, and G. K. Steinberg Mild Postischemic Hypothermia Prolongs the Time Window for Gene Therapy by Inhibiting Cytochrome c Release Stroke, February 1, 2004; 35(2): 572 - 577. [Abstract] [Full Text] [PDF]

				H. Deng, H. S. Han, D. Cheng, G. H. Sun, and M. A. Yenari Mild Hypothermia Inhibits Inflammation After Experimental Stroke and Brain Inflammation Stroke, October 1, 2003; 34(10): 2495 - 2501. [Abstract] [Full Text] [PDF]

				M. A. YENARI, H. ZHAO, R. G. GIFFARD, R. A. SOBEL, R. M. SAPOLSKY, and G. K. STEINBERG Gene Therapy and Hypothermia for Stroke Treatment Ann. N.Y. Acad. Sci., May 1, 2003; 993(1): 54 - 68. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help