Differences in the Evolution of the Ischemic Penumbra in Stroke-Prone Spontaneously Hypertensive and Wistar-Kyoto Rats

Abstract

Background and Purpose— Stroke-prone spontaneously hypertensive rats (SHRSP) are a highly pertinent stroke model with increased sensitivity to focal ischemia compared with the normotensive reference strain (Wistar-Kyoto rats; WKY). Study aims were to investigate temporal changes in the ischemic penumbra in SHRSP compared with WKY. Methods— Permanent middle cerebral artery occlusion was induced with an intraluminal filament. Diffusion- (DWI) and perfusion- (PWI) weighted magnetic resonance imaging was performed from 1 to 6 hours after stroke, with the PWI-DWI mismatch used to define the penumbra and thresholded apparent diffusion coefficient (ADC) maps used to define ischemic damage. Results— There was significantly more ischemic damage in SHRSP than in WKY from 1 to 6 hours after stroke. The perfusion deficit remained unchanged in WKY (39.9±6 mm 2 at 1 hour, 39.6±5.3 mm 2 at 6 hours) but surprisingly increased in SHRSP (43.9±9.2 mm 2 at 1 hour, 48.5±7.4 mm 2 at 6 hours; P =0.01). One hour after stroke, SHRSP had a significantly smaller penumbra (3.4±5.8 mm 2 ) than did WKY (9.7±3.8, P =0.03). In WKY, 56% of the 1-hour penumbra area was incorporated into the ADC lesion by 6 hours, whereas in SHRSP, the small penumbra remained static owing to the temporal increase in both ADC lesion size and perfusion deficit. Conclusions— First, SHRSP have significantly more ischemic damage and a smaller penumbra than do WKY within 1 hour of stroke; second, the penumbra is recruited into the ADC abnormality over time in both strains; and third, the expanding perfusion deficit in SHRSP predicts more tissue at risk of infarction. These results have important implications for management of stroke patients with preexisting hypertension and suggest ischemic damage could progress at a faster rate and over a longer time frame in the presence of hypertension.