Stroke, Vol 23, 1337-1347, Copyright © 1992 by American Heart Association
FC Barone, DB Schmidt, LM Hillegass, WJ Price, RF White, GZ Feuerstein, RK Clark, EV Lee, DE Griswold and HM Sarau
BACKGROUND AND PURPOSE: Neutrophils are critically involved with ischemia
and reperfusion injury in many tissues but have not been studied under
conditions of reperfusion after focal cerebral ischemia. The present
studies were conducted to confirm our previous observations quantifying
neutrophils in rat permanent focal stroke using a myeloperoxidase activity
assay and to extend them to transient ischemia with reperfusion. In
addition, leukotriene B4 receptor binding in ischemic tissue was evaluated
as a potential marker for inflammatory cell infiltration. METHODS:
Histological, enzymatic, and receptor binding techniques were used to
evaluate neutrophil infiltration and receptor binding in infarcted cortical
tissue 24 hours after permanent middle cerebral artery occlusion (n = 25)
or temporary occlusion for 80 (n = 12) or 160 (n = 22) minutes followed by
reperfusion for 24 hours in spontaneously hypertensive rats. RESULTS: Sham
surgery (n = 26) produced no changes in any parameter measured. After
permanent middle cerebral artery occlusion, neutrophil accumulation was
observed histologically, but the infiltration was moderate and typically
within and adjacent to blood vessels bordering the infarcted cortex. After
temporary middle cerebral artery occlusion with reperfusion, marked
neutrophil infiltration was observed throughout the infarcted cortex.
Myeloperoxidase activity was increased (p less than 0.05) after permanent
occlusion and to a greater extent after temporary occlusion with
reperfusion. Myeloperoxidase activity (units per gram wet weight) in
ischemic cortex was increased over that in nonischemic (control) cortex
32.2-fold, 54.6-fold, and 92.1-fold for permanent occlusion and 80 and 160
minutes of temporary occlusion with reperfusion, respectively (p less than
0.05). Sham surgery produced no changes in myeloperoxidase activity.
Leukotriene B4 receptor binding also was increased (p less than 0.05) after
focal ischemia and paralleled the increases in myeloperoxidase activity.
Ischemic cortex-specific receptor binding (femtomoles per milligram
protein) was 3.87 +/- 0.63 in sham-operated rats and 4.57 +/- 0.98, 8.98
+/- 1.11, and 11.12 +/- 1.63 for rats subjected to permanent occlusion and
80 and 160 minutes of temporary occlusion with reperfusion, respectively
(all p less than 0.05 different from sham-operated). Cortical
myeloperoxidase activity was significantly correlated with the degree of
cortical leukotriene B4 receptor binding (r = 0.66 and r = 0.79 in two
different studies, p less than 0.01). CONCLUSION: These data indicate that
neutrophils are involved in focal ischemia and that there is a dramatic
accumulation of neutrophils in infarcted tissue during reperfusion that can
be quantified using the myeloperoxidase activity assay. Leukotriene B4
receptor binding increases in infarcted tissue in a parallel manner, which
suggests that the increased leukotriene B4 binding is to receptors located
on the accumulating neutrophils.
ARTICLES
Reperfusion increases neutrophils and leukotriene B4 receptor binding in rat focal ischemia
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pa. 19406.
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