(Stroke. 1995;26:1093-1100.)
© 1995 American Heart Association, Inc.
Articles |
Cerebral Hypoxia-Ischemia Stimulates Cytokine Gene Expression in Perinatal Rats
From the Departments of Pediatrics and Neurology, University of Michigan, Ann Arbor.
Correspondence to Dr F.S. Silverstein, Room 8301, MSRB III Bldg, University of Michigan, Ann Arbor, MI 48109-0646. E-mail faye.silverstein@umich.edu.
Background and Purpose We tested the hypothesis that cerebral
hypoxia-ischemia selectively stimulates
interleukin-1ß (IL-1ß) and tumor necrosis factor-
(TNF-) gene
expression in brain regions susceptible to irreversible injury in
perinatal rats.
Methods To elicit focal hypoxic-ischemic brain injury,
7-day-old perinatal (P7) rats were subjected to right carotid artery
ligation followed by 3 hours of 8% O2 exposure and were
killed 0 to 48 hours after hypoxia. Regional tissue IL-1ß and
TNF- mRNA content were measured by reverse transcription followed by
polymerase chain reaction amplification (RT-PCR) in samples prepared
from cortex and hippocampus of the lesioned and contralateral
hemispheres. cDNAs were amplified with primers specific for IL-1ß,
TNF-, and the housekeeping gene glyceraldehyde-3-phosphate
dehydrogenase (GAPDH), which served as an internal control. The RT-PCR
products were subjected to Southern blot analysis and hybridized
with 32P-labeled gene-specific probes. Radioactivity was
measured in excised bands, and results were normalized on the basis of
levels of GAPDH expression.
Results In unlesioned P7 brain, IL-1ß mRNA was barely
detectable. In lesioned forebrain, there was a marked, transient
stimulation of IL-1ß mRNA expression, peaking at 4 hours after
hypoxia. Hybridization signal was increased 16- to 30-fold over
values from contralateral hemisphere samples in three independent
assays (P<.05 comparing values in left and right cortex and
in left and right hippocampus with the Kruskal-Wallis ranking test); by
24 hours after hypoxia, levels returned to normal. Similar
transient increases in TNF- mRNA expression were detected. In a
closely related model of perinatal brain injury elicited by focal
intracerebral
N-methyl-D-aspartate injection, there was a
corresponding acute stimulation of IL-1ß and TNF- mRNA expression
at 4 hours after injection.
Conclusions These results suggest that IL-1ß and TNF- may
play important roles in the response of the developing brain to acute
hypoxic-ischemic injury.
Key Words: interleukins • excitotoxicity • newborn • tumor necrosis factor • rats
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