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(Stroke. 2001;32:1750.)
© 2001 American Heart Association, Inc.

Original Contributions

Evolution of Cerebral Tumor Necrosis Factor- Production During Human Ischemic Stroke

Tiina Sairanen, MD; Olli Carpén, MD, PhD; Marja-Liisa Karjalainen-Lindsberg, MD, PhD; Anders Paetau, MD, PhD; Ursula Turpeinen, PhD; Markku Kaste, MD, PhD Perttu J. Lindsberg, MD, PhD

From the Department of Clinical Neurosciences, Helsinki University Central Hospital (T.S., M.K., P.J.L.); Department of Pathology, Haartman Institute (T.S., O.C., M.-L.K.-L., A.P.); Laboratory, Helsinki University Central Hospital (U.T.); and Neuroscience Program, Biomedicum (M.K., P.J.L.), Helsinki, Finland.

Reprint requests to Dr Tiina Sairanen, Department of Clinical Neurosciences, Helsinki University Central Hospital, Haartmaninkatu 4, FIN-00290 Helsinki, Finland. E-mail Tiina.sairanen{at}helsinki.fi

Background and Purpose—— Tumor necrosis factor- (TNF-) is detected in ischemic brain cells in experimental animal models and is believed to play an important role in apoptosis. However, the natural expression of TNF- during human stroke is not known.

Methods—— We examined TNF- immunohistochemistry and terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling (TUNEL) in brain samples of stroke victims (n=16) after variable survival (15 hours to 18 days). Systemic TNF- content from a separate cohort including severe or lethal stroke cases (n=26) was also assayed.

Results—— Neuronal TNF- was demonstrated from 0.6 to 5.4 days after the onset of stroke symptoms, peaking bilaterally during days 2 and 3. Bilateral glial TNF- immunoreactivity was detected during the acute phase, with the astrocytic TNF- expression dominating in later phases and persisting contralaterally to the infarct in more matured phases (17 to 18 days). Invading inflammatory cells were TNF- immunopositive beginning on the third day. Besides, vascular wall structures showed immunoreactivity sporadically. TNF- levels were mostly nondetectable in peripheral blood. TUNEL labeling and TNF- staining overlapped, although not completely, during the first days.

Conclusions—— The data support the hypothesis that TNF- may be involved both in the acute propagation of inflammatory processes and cell death and possibly in the more delayed reconstitutive processes of human ischemic stroke.

Editorial Comment

David F. Cechetto, PhD; Guest Editor

Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada

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