Reperfusion following focal stroke hastens inflammation and resolution of ischemic injured tissue.
Previously, we described cellular changes following Permanent Middle Cerebral Artery Occlusion (PMCAO) in spontaneously hypertensive rats. Ischemic changes following PMCAO included a time-related focal pan necrosis, inflammatory cell infiltration, gliosis, and eventual loss of necrotic tissue post PMCAO. We have now characterized changes which occur after Temporary Middle Cerebral Artery Occlusion (TMCAO; 80 or 160 min) followed by reperfusion and compared these changes to those which occur following PMCAO. TMCAO with reperfusion results in cortical infarcts which vary in size in an occlusion-time-dependent manner. After 1 h of reperfusion, ischemic changes were observed histologically, including microhemorrhages and the beginning of a slight inflammatory infiltration in and around the meningeal vasculature. This infiltrate consisted primarily of neutrophils, which by 6 h of reperfusion was significant with infiltration from deep blood vessels into brain tissue, including the presence of some monocytes adhering within blood vessels. Neutrophil infiltration occurred sooner and to a greater extent in reperfused tissues than in permanently occluded tissues, where it only began at 12 h post PMCAO. As occurred following PMCAO, increased Glial Fibrillary Acidic Protein (GFAP) immunoreactivity indicating astrogliosis was first observed at 12 h postTMCAO. Over 1-3 days of reperfusion, a heavy macrophage infiltrate was observed in the reperfused tissues in addition to a continued influx of neutrophils. Following 5 days of reperfusion, the lesion was completely replaced with inflammatory cells, of which macrophages predominated. Unlike PMCAO, which resulted in focal spots of neutrophil accumulation, neutrophils were more distributed throughout the infarcted cortex following TMCAO.(ABSTRACT TRUNCATED AT 250 WORDS)
Clark
R K
RK
Department of Cellular Biochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406.
Lee
E V
EV
White
R F
RF
Jonak
Z L
ZL
Feuerstein
G Z
GZ
Barone
F C
FC
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000473:pathology*; D002561:Cerebrovascular Disorders / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D002546:Ischemic Attack, Transient / Q000473:pathology*; D008264:Macrophages; D008297:Male; D009336:Necrosis; D009504:Neutrophils; D051381:Rats; D011918:Rats, Inbred SHR; D015424:Reperfusion; D015427:Reperfusion Injury / Q000473:pathology