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

Abstract

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 hour of unilateral middle cerebral artery occlusion (MCAO), 1 hour after reperfusion, and 1 day, 4 days and 7 days after MCAO. Regional CBF 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 suggests that impaired CBF regulation and relatively high CBF threshold for ischemia are strong contributors to the increased susceptibility of SHR to ischemic stroke.

Effects of hyperoxia on 18F-fluoro-misonidazole brain uptake and tissue oxygen tension following middle cerebral artery occlusion in rodents: Pilot studies

“…One might also argue that such very low P t O 2 values indicate that the affected tissue is already irreversibly damaged (i.e., the ‘core’), and hence that NBO might not have enhanced P t O 2 in such conditions, resulting in unchanged FMISO lesion volumes. However, even though SHRs have worse hypoperfusion [ 33 – 35 ] and hypoxia after MCAo than Wistar rats (as shown here), they do have an extensive penumbra initially [ 33 – 35 , 62 ], and early interventions such as reperfusion and hyperoxia but also drugs do salvage the penumbra and reduce final infarct in SHRs [ 31 , 47 , 63 – 66 ], indicating that NBO should have affected FMISO uptake and retention, albeit probably less so than in Wistar rats.…”

Blood–brain and blood–cerebrospinal fluid barrier permeability in spontaneously hypertensive rats

“…Finally, the brain microvasculature of SHR was not affected in terms of vessel volume, vessel diameter, and the number of branches. From this we conclude that several established features of mature SHR, including the lower brain weight, larger ventricular volume [ 19 , 20 ], small artery remodelling [ 12 ], and increased sensitivity to stroke [ 32 ] are not paralleled by a physical loss of BBB and BCSFB integrity.…”

Arterial Hypertension Aggravates Innate Immune Responses after Experimental Stroke

“…To investigate this hypothesis, we compared stroke development, cerebral AM expression and neuroinflammation in spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (WKYs). Due to cerebral microangiopathy and impaired cerebral blood flow regulation, traditional stroke models such as transient or permanent middle cerebral artery occlusion (MCAO) generally cause larger infarcts in hypertensive rats ( Hom et al, 2007 ; De Geyter et al, 2012 ; Kang et al, 2014 ). This would, however, confound the investigation of secondary immune-related changes.…”