Reperfusion Cellular Injury in an Animal Model of Transient Ischemia

Abstract

BACKGROUND AND PURPOSE: Early thrombolytic therapy is encouraged in hyperacute stroke, although this might result in delayed reperfusion injury. Our purpose was to investigate the serial changes in cerebral perfusion following transient ischemia by means of MR imaging and to correlate them with the histologic findings obtained by using the TdT-mediated dUTP-biotin nick-end labeling (TUNEL) assay.

METHODS: One-hour transient occlusion of the middle cerebral artery was produced in 10 cats. Serial perfusion-weighted MR imaging was performed for 3 days after reperfusion. The reperfusion characteristics in each region of the brain were classified into four groups according to the serial perfusion MR imaging status: normal perfusion (N), continuous hyperperfusion (I), early hyperperfusion and gradual decrease (II), and persistent hypoperfusion (III). After the last imaging session, a specimen was obtained, and TUNEL staining was performed. TUNEL-positive cells were counted under a high-power-field (HPF) light microscope (×200). The degree of TUNEL positivity was compared among the four reperfusion groups classified on the basis of serial perfusion-weighted imaging findings.

RESULTS: Group N had 16.8 ± 5.1 TUNEL-positive cells per HPF. Groups I and II had a statistically significant increase in TUNEL positivity (39.5 ± 13.4 and 43.6 ± 16.7 cells per HPF; P < .01, one-way analysis of variance), whereas group III had a statistically insignificant increase in TUNEL positivity (23.3 ± 6.9 cells per HPF).

CONCLUSION: Reperfusion followed by hyperperfusion induced cellular damage, although the initial MR imaging findings were normal. The inclusion of anti-reperfusion injury therapy should be considered in thrombolytic treatment.