Impaired CBF regulation and high CBF threshold contribute to the increased sensitivity of spontaneously hypertensive rats to cerebral ischemia

- We investigated the severity of transient ischemic stroke in SHR and WKY rats.
- During ischemia, perfusion-deficient lesions did not differ between WKY and SHR.
- In WKY, the final ischemic lesion was smaller than the perfusion-deficient lesion.
- In SHR, most of the perfusion-deficient lesion became the final ischemic lesion.
- Harmed CBF control, higher floor contribute to larger SHR susceptibility to stroke.

The correlation between temporal changes of regional cerebral blood flow (rCBF) and the severity of transient ischemic stroke in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) was investigated using T2-, diffusion- and perfusion-weighted magnetic resonance imaging at six different time points: before and during 1 h of unilateral middle cerebral artery occlusion (MCAO), 1 h after reperfusion, and 1 day, 4 days and 7 days after MCAO. rCBF values were measured in both hemispheres, and the perfusion-deficient lesion (PDL) was defined as the area of the brain with a 57% or more reduction in basal CBF. Within the PDL, regions were further refined as ischemic core (rCBF = 0-6 mL/100 g/min), ischemic penumbra (rCBF = 6-15 mL/100 g/min) and benign oligemia (rCBF > 15 mL/100 g/min). SHR and WKY had identical initial volume of the PDLs (WKY: 32.52 ± 4.08% vs. SHR: 33.95 ± 3.68%; P > 0.05) and the maximum rCBF measured within those lesions (WKY: 38.20 ± 3.57 mL/100 g/min vs. SHR: 38.46 ± 6.22 mL/100 g/min; P > 0.05) during MCAO. However, in SHR virtually all of the PDL progressed to become the final ischemic lesion (33.02 ± 5.41%, P > 0.05), while the final ischemic lesion volume of WKY (12.62 ± 9.19%) was significantly smaller than their original PDL (P < 0.01) and similar to the ischemic core (13.13 ± 2.96%, P > 0.05). The region with the lowest range of rCBF was positively correlated with the final ischemic lesion volume (r = 0.716, P < 0.01). Both during ischemia and after reperfusion, rCBF in either ipsilesional and contralesional brain hemispheres of SHR could not be restored to pre-ischemic levels, and remained lower than in WKY until up to 4 days after MCAO. The data suggest that impaired CBF regulation and relatively high CBF threshold for ischemia are strong contributors to the increased susceptibility of SHR to ischemic stroke.