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(Stroke. 2006;37:1116.)
© 2006 American Heart Association, Inc.

Research Reports

Interferon-ß Fails to Protect in a Model of Transient Focal Stroke

Carolina M. Maier, PhD; Fengshan Yu, MD; Tatsuro Nishi, MD, PhD; Stephanie J. Lathrop, PhD Pak H. Chan, PhD

From the Department of Neurosurgery (C.M.M., F.Y., T.N., P.H.C.), Department of Neurology and Neurological Sciences and Program in Neurosciences, Stanford University School of Medicine, Stanford, Calif; and Maxygen, Inc (S.J.L.), Redwood City, Calif.

Correspondence to Pak H. Chan, PhD, Neurosurgical Laboratories, Stanford University, 1201 Welch Rd, MSLS #P314, Stanford, CA 94305-5487. E-mail phchan{at}stanford.edu

Background and Purpose— Compelling evidence supporting the role of inflammation in the development of cerebral infarction has focused attention on the potential of antiinflammatory treatment strategies for stroke. Interferon (IFN)-ß, an immunomodulatory agent approved for treatment of multiple sclerosis, is being evaluated in a phase I clinical trial in acute ischemic stroke. In the present study, we evaluated the effects of wild-type rat IFN-ß and its pegylated counterpart (PEG-IFN-ß) in a model of focal ischemia and reperfusion.

Methods— After 60 minutes of middle cerebral artery occlusion, rats (n=12/group) were treated with IV tail injections of 8 or 16 µg of IFN-ß in 300 µL of PBS once daily for 3 or 7 days or with IV or SC injections of PEG-IFN-ß for 1 day. The animals were assessed daily for weight and for neurological findings. Additional animals underwent complete hematology and chemistry profiles, as well as complete multiorgan necropsy studies. All of the brain tissue was evaluated for assessment of infarct areas, neutrophil infiltration, and presence of hemorrhagic transformations.

Results— IFN-ß and PEG-IFN-ß failed to protect against experimental ischemic brain injury as assessed by histopathology and neurological outcome. Furthermore, IFN-ß treatment was associated with significant weight loss and alterations in hematology and chemistry profiles.

Conclusions— Our results suggest that additional preclinical studies are warranted.

Key Words: inflammation • interferon ß • ischemia • neuroprotection