This Article Order Full text via Infotrieve Services Similar articles in this journal 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 Google Scholar Google Scholar Articles by Tani, M. Articles by Ransohoff, R. M. Search for Related Content PubMed PubMed Citation Articles by Tani, M. Articles by Ransohoff, R. M.

American Journal of Pathology, Vol 148, 889-896, Copyright © 1996 by American Society for Investigative Pathology

REGULAR ARTICLES

In situ hybridization analysis of glial fibrillary acidic protein mRNA reveals evidence of biphasic astrocyte activation during acute experimental autoimmune encephalomyelitis

M Tani, AR Glabinski, VK Tuohy, MH Stoler, ML Estes and RM Ransohoff
Department of Neurosciences, Cleveland Clinic Foundation, Ohio 44195, USA

Reactive astrogliosis is a prominent pathological feature of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. It is characterized by hypertrophy of astrocytes with increased content of glial fibrillary acidic protein (GFAP.) Studies of reactive astrocytes in acute experimental autoimmune encephalomyelitis have been complicated by the observation that the diffuse increase in GFAP immunohistochemical staining at the onset of central nervous system inflammation does not parallel the gradual increase in GFAP content probably because tissue edema enhances GFAP immunostaining. To characterize changes in GFAP expression, we performed in situ hybridization at 3- to 7-day intervals during the course of acute murine experimental autoimmune encephalomyelitis. We found a biphasic course of GFAP expression: an early phase of astrocyte reaction surrounding perivascular inflammatory cuffs and submeningeal infiltrates at the onset of central nervous system inflammation and clinical disease and a later phase of increased GFAP mRNA expression in regions of demyelination during resolution of inflammation and clinical improvement. IP-10, a member of a family of proinflammatory chemoattractant cytokines called chemokines, was expressed by astrocytes in a similar distribution as those expressing increased GFAP mRNA in the early phase of inflammation but was no detected in astrocytes in the later phase of activation. These results indicate that location and function of reactive astrocytes may vary during the course of immune-mediated demyelination.

This article has been cited by other articles:

				F. Monnet-Tschudi, M-G. Zurich, and P. Honegger Neurotoxicant-induced inflammatory response in three-dimensional brain cell cultures Human and Experimental Toxicology, April 1, 2007; 26(4): 339 - 346. [Abstract] [PDF]

				Y. Zhang, Y.-T. Chen, S. Xie, L. Wang, Y.-F. Lee, S.-S. Chang, and C. Chang Loss of Testicular Orphan Receptor 4 Impairs Normal Myelination in Mouse Forebrain Mol. Endocrinol., April 1, 2007; 21(4): 908 - 920. [Abstract] [Full Text] [PDF]

				S. Brahmachari, Y. K. Fung, and K. Pahan Induction of glial fibrillary acidic protein expression in astrocytes by nitric oxide. J. Neurosci., May 3, 2006; 26(18): 4930 - 4939. [Abstract] [Full Text] [PDF]

				N. Kawakami, S. Lassmann, Z. Li, F. Odoardi, T. Ritter, T. Ziemssen, W. E.F. Klinkert, J. W. Ellwart, M. Bradl, K. Krivacic, et al. The Activation Status of Neuroantigen-specific T Cells in the Target Organ Determines the Clinical Outcome of Autoimmune Encephalomyelitis J. Exp. Med., January 20, 2004; 199(2): 185 - 197. [Abstract] [Full Text] [PDF]

				T. S. Olson and K. Ley Chemokines and chemokine receptors in leukocyte trafficking Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2002; 283(1): R7 - R28. [Abstract] [Full Text] [PDF]

				B. C. Kieseier, M. Tani, D. Mahad, N. Oka, T. Ho, N. Woodroofe, J. W. Griffin, K. V. Toyka, R. M. Ransohoff, and H.-P. Hartung Chemokines and chemokine receptors in inflammatory demyelinating neuropathies: a central role for IP-10 Brain, April 1, 2002; 125(4): 823 - 834. [Abstract] [Full Text] [PDF]

				Z.-H. L. ZHOU, Y. HAN, T. WEI, S. ARAS, P. CHATURVEDI, S. TYLER, M. R. S. RANI, and R. M. RANSOHOFF Regulation of monocyte chemoattractant protein (MCP)-1 transcription by interferon-gamma (IFN-{gamma}) in human astrocytoma cells: postinduction refractory state of the gene, governed by its upstream elements FASEB J, February 1, 2001; 15(2): 383 - 392. [Abstract] [Full Text] [PDF]

				G X Zhang, C M Baker, D L Kolson, and A M Rostami Chemokines and chemokine receptors in the pathogenesis of multiple sclerosis Multiple Sclerosis, February 1, 2000; 6(1): 3 - 13. [Abstract] [PDF]

				Y. Persidsky, A. Ghorpade, J. Rasmussen, J. Limoges, X. J. Liu, M. Stins, M. Fiala, D. Way, K. S. Kim, M. H. Witte, et al. Microglial and Astrocyte Chemokines Regulate Monocyte Migration through the Blood-Brain Barrier in Human Immunodeficiency Virus-1 Encephalitis Am. J. Pathol., November 1, 1999; 155(5): 1599 - 1611. [Abstract] [Full Text] [PDF]

				J. P. Palma, R. L. Yauch, S. Lang, and B. S. Kim Potential Role of CD4+ T Cell-Mediated Apoptosis of Activated Astrocytes in Theiler's Virus-Induced Demyelination J. Immunol., June 1, 1999; 162(11): 6543 - 6551. [Abstract] [Full Text] [PDF]