Ischemia-reperfusion
brain injury initiates an inflammatory response involving the expression of adhesion molecules and
cytokines, some of which are regulated by the nuclear
transcription factor NF-kappaB. In this study the authors examined
mRNA expression levels for several important genes associated with
inflammation at five time points (3, 6, 12, 24, and 72 hours) after transient
middle cerebral artery occlusion (MCAO) in Sprague-Dawley rats. A sensitive and quantitative technique (TaqMan real-time QRT-PCR) was used to simultaneously measure
mRNA levels for key
cell adhesion molecules and inflammatory
cytokines. Gene expression increased significantly in the injured hemisphere for
interleukin (IL)-1beta (12-fold increase at 24 hours),
IL-6 (25-fold increase at 6 hours) and
ICAM-1 (4-fold increase at 24 hours), and the interhemispheric differences for these genes were significant for every time point examined (P < 0.05 for all values).
Tumor necrosis factor-alpha mRNA was upregulated in the injured versus uninjured hemisphere from 3 to 24 hours (5-fold increase at 6 hours), while
E-selectin showed a significant increase in
mRNA levels from 6 to 24 hours after MCAO (10-fold increase at 6 hours) (P < 0.05 for all values).
VCAM-1 mRNA levels did not respond differentially to injury at any time point between the two brain hemispheres. At all time points examined, activated
NF-kappaB immunoreactivity was observed in cells throughout the
infarct-damaged tissue. These results are consistent with the proinflammatory properties of the induced molecules, which are involved in the initiation of the inflammatory cascade, and may thus contribute to secondary cellular responses that lead to further brain damage.