Journal of NeuroVirology, 8: 452±458, 2002 c ° 2002 Taylor & Francis ISSN 1355±0284/02 $12.00+.00 DOI: 10.1080/13550280290100833 Short Communication ICAM-1 is crucial for protection from TMEV-induced neuronal damage but not demyelination Kristen M Drescher, 1 Laurie J Zoecklein, 2 and Moses Rodriguez 2 1 Department of Medical Microbiology and Immunology, Creighton University, Omaha, Nebraska, USA; 2 Department of Immunology and Neurology, Mayo Clinic/Foundation, Rochester, Minnesota, USA Previous work has suggested that the factors protecting mice from Theiler’s murine encephalomyelitis virus (TMEV)-induced spinal cord demyelination are distinct from those involved in protection of the brain during the acute encephalitic phase. In this study, we examined the requirement for intercellu- lar adhesion molecule-1 (ICAM-1) in both of these processes. During the acute phase of infection (days 7 to 10 after intracerebral infection with TMEV), no differences in brain or spinal cord pathology or virus burdens were observed between ICAM-1–knockout mice and the infected immunocompetent control mice of a similar background. Examination of brain pathology later in infec- tion (that is, day 45 post infection [p.i.]) revealed that ICAM-1–decient mice experienced increased levels of pathology in gray matter regions of the brain. We observed an increase in striatal damage and meningeal inammation in the brains of TMEV-infected ICAM-1–knockout mice compared to C57BL/6J mice. Despite the increase in brain pathology, no immunoreactivity to viral antigens was detected, suggesting that the virus had been cleared by this time. Resistance to demyelination was similar in both groups, indicating that the re- sulting immune response was sufcient for protection of the spinal cord white matter. Journal of NeuroVirology (2002) 8, 452–458. Keywords: brain pathology; demyelination; ICAM-1; inammation; TMEV Under normal conditions, minimal adhesion mole- cule expression is detected in the central nervous sys- tem (CNS). Following infection, injury, or induction of autoimmune disease, the host rapidly upregulates intercellular adhesion molecule-1 (ICAM-1) in the CNS (Raine and Cannella, 1992; Kraus et al, 1998; Mycko et al, 1998; McDonnell et al, 1999). ICAM-1 expression on endothelial cells is integral to lym- phocyte migration (Reiss and Engelhardt, 1999). CNS resident cells such as astrocytes and microglia (Sobel et al, 1990; Shrikant et al, 1994; Drescher and Whittum-Hudson, 1996) also upregulate ICAM-1 dur- ing inammatory reactions. In these cells, ICAM-1 Address correspondence to Moses Rodriguez, Department of Immunology, Mayo Clinic, Guggenheim 428, 200 First Street, SW, Rochester, MN 55905, USA. E-mail: rodriguez.moses@mayo.edu These studies were supported by NIH grants P01 NS38468 (MR) and R01 NS32129 (MR), a grant from the Health Futures Founda- tion (KMD), and the American Cancer Society (KMD). Received 4 August 2001; revised 28 May 2002; accepted 10 July 2002. is presumed to facilitate antigen presentation by in- teracting with leukocyte functional antigen (LFA-1) on T lymphocytes. Although the ability of the host to modulate expression of ICAM-1 may provide a protective advantage to the host, inappropriate expression of adhesion molecules may contribute (or be associated with) to irreversible pathology in sites such as the CNS (Raine and Cannella, 1992; Kraus et al, 1998; Mycko et al, 1998; McDonnell et al, 1999). In vitro, expression of ICAM is enhanced by proinammatory soluble mediators such as tumor necrosis factor alpha (TNF-®), interferon gamma (IFN-° ), and interleukin (IL)-1¯ (Satoh et al, 1991; Shrikant et al, 1994; Hery et al, 1995; Drescher and Whittum-Hudson, 1996; Kyrkanides et al, 1999), suggesting one mechanism by which this molecule may be up-regulated during inammatory processes. Several investigators have suggested that ICAM- 1 is a participant in the development of pathology in multiple sclerosis (MS), the most common de- myelinating disease of humans (Kraus et al, 1998;