Magnetic resonance imaging quantification of regional cerebral blood flow and cerebrovascular reactivity to carbon dioxide in normotensive and hypertensive rats

Abstract

Hypertension afflicts 25% of the general population and over 50% of the elderly. In the present work, arterial spin labeling MRI was used to non-invasively quantify regional cerebral blood flow (CBF), cerebrovascular resistance and CO2 reactivity in spontaneously hypertensive rats (SHR) and in normotensive Wistar Kyoto rats (WKY), at two different ages (3 months and 10 months) and under the effects of two anesthetics, α-chloralose and 2% isoflurane (1.5 MAC). Repeated CBF measurements were highly consistent, differing by less than 10% and 18% within and across animals, respectively. Under α-chloralose, whole brain CBF at normocapnia did not differ between groups (young WKY: 61±3ml/100g/min; adult WKY: 62±4ml/100g/min; young SHR: 70±9ml/100g/min; adult SHR: 69±8ml/100g/min), indicating normal cerebral autoregulation in SHR. At hypercapnia, CBF values increased significantly, and a linear relationship between CBF and PaCO2 levels was observed. In contrast, 2% isoflurane impaired cerebral autoregulation. Whole brain CBF in SHR was significantly higher than in WKY rats at normocapnia (young SHR: 139±25ml/100g/min; adult SHR: 104±23ml/100g/min; young WKY: 55±9ml/100g/min; adult WKY: 71±19ml/100g/min). CBF values increased significantly with increasing CO2; however, there was a clear saturation of CBF at PaCO2 levels greater than 70 mmHg in both young and adult rats, regardless of absolute CBF values, suggesting that isoflurane interferes with the vasodilatory mechanisms of CO2. This behavior was observed for both cortical and subcortical structures. Under either anesthetic, CO2 reactivity values in adult SHR were decreased, confirming that hypertension, when combined with age, increases cerebrovascular resistance and reduces cerebrovascular compliance.

Cortical Selective Neuronal Loss, Impaired Behavior, and Normal Magnetic Resonance Imaging in a New Rat Model of True Transient Ischemic Attacks

“…Because pure SNL was already present at day 7, it does not represent a delayed phenomenon; however, longitudinal studies would be worth performing to determine the precise time course of postischemic SNL. Consistent with the histopathologic literature on SHR, 21,22 there was no evidence in this study of SNL or microinfarcts, nor of any MRI changes, in the contralesional hemisphere, so the observed changes can be confidently ascribed to the MCAo. However, SHRs are known to develop brain vasculature changes secondary to chronic hypertension that make them particularly susceptible to ischemic injury.…”

“…However, SHRs are known to develop brain vasculature changes secondary to chronic hypertension that make them particularly susceptible to ischemic injury. 17,18,21,22 Our model mimics true TIA not only as no MRI changes were detected at any postreperfusion time point, but also because neurological examination was normal throughout. However, finer behavioral tests disclosed significant sensorimotor dysfunction still incompletely recovered at 4 weeks.…”

Regional Cerebral Blood Flow and Arterial Blood Volume and Their Reactivity to Hypercapnia in Hypertensive and Normotensive Rats

“…29 We also observed a similar baseline CBF in SHR and WKY animals, consistent with some human studies 1,11-14 but not others in which hypertensive subjects demonstrated a slight reduction in CBF. [8][9][10] At the same time, in other studies using the SHR and WKY models, hypertensive animals had a much higher baseline CBF value than control animals under 2% isoflurane (104 ± 23 versus 71±19 mL/100 g per minute 30 and 150±20 versus120±20 mL/ 100 g per minute. 31 ) However, the fact that we used B1% isoflurane while the other studies used 2% may account for this difference in results.…”

“…31 ) However, the fact that we used B1% isoflurane while the other studies used 2% may account for this difference in results. 30 The 2% isoflurane level, typical for surgical procedures, could impair cerebrovascular regulation during a long experiment. Indeed, Leoni et al 30 and colleagues observed a decrease in MABP during hypercapnia in animals anesthetized with 2% isoflurane, unlike our study.…”

Hypoxia-Induced Neuroinflammatory White-Matter Injury Reduced by Minocycline in SHR/SP

“…This results in hypoxic hypoperfusion, which is occurring with long-standing, poorly treated hypertension in humans. 38 We propose that the development of WM damage in SHR/SP/UCAO/ JPD is a multiphase process with several sequential events required to produce the final tissue injury. This process can be visualized as a series of 'hits': (1) initially, the chronic hypertension causes vessel lumen narrowing and loss of normal autoregulation of the blood vessels, which leads to hypoperfusion and hypoxia in the vulnerable deep WM; (2) hypoxia leads to production of HIF-1α, inducing an inflammatory response; and (3) finally, there is production of MMPs, disrupting the tight junctions and extracellular matrix with opening of the BBB.…”