Impact of Genetic and Renovascular Chronic Arterial Hypertension on the Acute Spatiotemporal Evolution of the Ischemic Penumbra: A Sequential Study with MRI in the Rat

Abstract

Although chronic arterial hypertension (CAH) increases the risk of stroke and the severity of the resultant lesion, it is rarely integrated in preclinical studies. Here, we analyzed the impact of CAH on the acute spatiotemporal evolution of the ischemic penumbra as defined by the perfusion-weighted imaging/diffusion-weighted imaging mismatch. Sequential 7T-MRI examinations were performed from 30 minutes up to 4 hours after permanent cerebral ischemia in genetically hypertensive rats (spontaneously hypertensive rats, SHR), renovascular-hypertensive rats (RH-WKY), and their normotensive controls (Wistar-Kyoto rats, WKY). The apparent diffusion coefficient (ADC)-defined lesion was larger in hypertensive rats than in normotensive animals as early as 30 minutes after the ischemia. The ischemic penumbra was smaller in both genetically and renovascular-hypertensive rats (at 30 minutes; SHR = 66 ± 25 mm 3 , RH-WKY = 55 ± 17 mm 3 versus WKY = 117 ± 14 mm 3 ; P < 0.008) and there was no significant difference between the perfusion deficit and ADC lesion (mismatch definition of penumbra) as early as 90 minutes after the occlusion. Genetic hypertension and induced renovascular hypertension resulted in larger lesion and smaller penumbra that vanished rapidly. These data support the need to integrate CAH in preclinical studies relative to the treatment of stroke, as failure to do so may lead to preclinical results nonpredictive of clinical trials, which include hypertensive patients.

Penumbra Detection using PWI/DWI Mismatch MRI in a Rat Stroke Model with and without Comorbidity: Comparison of Methods

“…The phenomenon of negative mismatch has been identified previously in rodent stroke models (Foley et al, 2010;Letourneur et al, 2011) and may potentially occur as a consequence of peri-infarct spreading depolarizations from the ischemic core, increasing cellular injury in adjacent oligemic tissue, and extending the outer boundary of injured tissue beyond the perfusion deficit. High levels of potassium ions and glutamate in the ischemic core can actively induce tissue depolarization, ionic imbalances and glutamate spread into adjacent tissue and peri-infarct depolarizations can originate in the striatum in rats (Hartings et al, 2003).…”

“…Similarly, our data may have failed to recognize potential strain differences in penumbra volume since we could not examine the full extent of the rostral and caudal poles of the penumbra due to the time constraints associated with CBF data acquisition. Letourneur et al (2011) showed a reduced mismatch volume in SHR and renovascular hypertensive (RH) WKY rats compared with normotensive WKY rats from 30 minutes to 4 hours after MCAO. Our data show that penumbra volume was not significantly different between WKY and SHRSP from 1 to 4 hours using volumetric mismatch, spatial mismatch, or ADC lesion growth.…”

“…Mismatch volume has previously been determined in rodent stroke models using the volumetric method (Meng et al, 2004) and by spatial coregistration of MRI perfusion and diffusion images (Letourneur et al, 2011). In the current study, spatial assessment of penumbra gave rise to a measurable mismatch volume in SHRSP and WKY and although the SHRSP strain showed a significantly larger perfusion deficit and ADC-derived lesion, mismatch volume was not significantly different between strains from 1 to 4 hours after MCAO.…”

Chronic arterial hypertension impedes glioma growth: a multiparametric MRI study in the rat

“…All animal experiments were carried out under the previous European directive (86/609/EEC) as enacted in the national legislation. Individual licenses to investigate SR (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26), MB (14-71), JT , EP (14-79), OT (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) and SV are held and the study was approved by the regional ethical committee for animal research and health-care 'Comité Régional d'Éthique en matière d'Expérimentation Animale pour la Normandie' (CEEAN, agreement no. 0507-02).…”

Ischemic penumbra as a trigger for intracranial pressure rise – A potential cause for collateral failure and infarct progression?

“…There are large differences in the volume of penumbral tissue and the rate it is incorporated into the infarct core following occlusion of the MCA in different rat strains. [23][24][25][26] This is generally thought to be due to differences in the residual blood flow to the ischemic brain via the leptomeningeal collateral circulation. 27 We have previously demonstrated that inadvertent occlusion of the AChA, an important internal collateral supply to the MCA results in larger 24-h histological infarct volumes.…”