Background and Purpose-Tumor necrosis factor-alpha (TNF-alpha) is detected
in ischemic brain cells in experimental animal models and is believed to pl
ay an important role in apoptosis. However, the natural expression of TNF-a
lpha during human stroke is not known.
Methods-We examined TNF-alpha immunohistochemistry and terminal deoxynucleo
tidyl transferase-mediated dUTP nick-end labeling (TUNEL) in brain samples
of stroke victims (n = 16) after variable survival (15 hours to 18 days). S
ystemic TNF-alpha content from a separate cohort including severe or lethal
stroke cases (n=26) was also assayed.
Results-Neuronal TNF-alpha was demonstrated from 0.6 to 5.4 days after the
onset of stroke symptoms, peaking bilaterally during days 2 and 3. Bilatera
l glial TNF-alpha immunoreactivity was detected during the acute phase, wit
h the astrocytic TNF-alpha expression dominating in later phases and persis
ting contralaterally to the infarct in more matured phases (17 to 18 days).
Invading inflammatory cells were TNF-alpha immunopositive beginning on the
third day. Besides, vascular wall structures showed immunoreactivity spora
dically. TNF-alpha levels were mostly nondetectable in peripheral blood. TU
NEL labeling and TNF-alpha staining overlapped, although not completely, du
ring the first days.
Conclusions-The data support the hypothesis that TNF-alpha 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 str
oke.