Evolution of cerebral tumor necrosis factor-alpha production during human ischemic stroke.
OBJECTIVE
Tumor necrosis factor-alpha (TNF-alpha) 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-alpha during human stroke is not known.


METHODS
We examined TNF-alpha 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-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. Bilateral glial TNF-alpha immunoreactivity was detected during the acute phase, with the astrocytic TNF-alpha expression dominating in later phases and persisting 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 sporadically. TNF-alpha levels were mostly nondetectable in peripheral blood. TUNEL labeling and TNF-alpha staining overlapped, although not completely, during 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 stroke.
Sairanen
T
T
Department of Clinical Neurosciences, Helsinki University Central Hospital, University of Western Ontario, London, Ontario, Canada.
Carpén
O
O
Karjalainen-Lindsberg
M L
ML
Paetau
A
A
Turpeinen
U
U
Kaste
M
M
Lindsberg
P J
PJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005453:Fluorescence; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008833:Microcirculation / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010586:Phagocytes / Q000378:metabolism / Q000473:pathology; D020521:Stroke / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha