Reperfusion Cellular Injury in Ischemic Stroke: Monitoring with Diffusion and Perfusion MRI

Abstract

Ziele: The purpose of this study was to investigate the serial changes in cerebral perfusion following transient ischemia by means of perfusion and diffusion weighted MRI. We also investigated the neuroprotective effect of agmatine in the case of reperfusion hyperemia by TUNEL assay. Methode: The one hour transient MCA occlusion model was produced in 25 cats (10 controls and 15 agmatine treated cats). Serial perfusion MRI (PWI) was performed for 3 days after reperfusion. The reperfusion characteristics in each region of the brain were classified into 4 groups according to the serial perfusion MRI status, with the categories being (N) normal perfusion, (I) continuous hyperperfusion, (II) early hyperperfusion and gradual decrease and (III) persistent hypoperfusion. After the last imaging session, a specimen was obtained and TUNEL staining was performed. TUNEL positive cells were counted on high power field (HPF) light microscope (x200). The degree of TUNEL positivity was compared among the four reperfusion groups on the serial PWI images. Ergebnis: In the control group, T2- or DWI abnormalities were definable in all cases. In comparison, 5/15 cats in the agmatine treated group developed definite signal intensity changes on the T2- or DWI. Histologically, the total number of TUNEL positive cells were significantly smaller in the agmatine treated cats compared to the control ischemia cats (17.4±34.8 vs. 35.7±15.8, p<0.05). In the control ischemia cats, areas of type I and II reperfusions showed a significantly larger number of TUNEL positive cells compared to the type N areas. However, in the agmatine treated cats, no significant difference in the number of TUNEL positive cells between the reperfusion types were seen. The number of TUNEL positive cells in the areas of type I and II reperfusions were significantly lower in the agmatine treated group than in the control ischemia group. The area of severe ischemic neuronal damage on H&E stain was also significantly attenuated in the agmatine treated group (25.6±10.9% vs. 16.7±4.9%, p<0.05). Schlussfolgerung: In conclusion, by using an MR-based image analysis of the reperfusion pattern and ischemia with histologic confirmation of the cellular damage, the neuroprotective effects of agmatine against ischemia and reperfusion injury has been shown in a transient ischemic cat model.