Abstract
Hematocrit (Hct) determines the ability of blood to carry oxygen. While changes in systemic Hct are known to impact stroke or tumor control, changes in local (tissue) Hct (tHct) induced by these diseases have however received little attention. In this study, we evaluate tHct in acute stroke and in glioma models using a new approach to map tHct across the brain, a dual isotope autoradiography, based on injections of 125I-labeled albumin and 99mTc-lalbeled red blood cells in the same animal. For validation purpose, tHct was mapped in the rat brain (i) under physiological conditions, (ii) following erythropoietin injection, and (iii) following hemodilution. Then, tHct was then mapped in stroke (middle cerebral artery occlusion) and tumor models (9LGS and C6). The mean tHct values observed in healthy brains (tHct = 29 ± 1.3%), were modified as expected by erythropoietin (tHct = 36.7 ± 2.6%) and hemodilution (tHct = 24.2 ± 2.4%). Using the proposed method, we observed a local reduction, spatially heterogeneous, in tHct following acute stroke (tHct = 19.5 ± 2.5%) and in both glioma models (9LGS: tHct = 18.5 ± 2.3%, C6: tHct = 16.1 ± 1.2%). This reduction and this heterogeneity in tHct observed in stroke and glioma raises methodological issues in perfusion imaging techniques where tHct is generally overlooked and could impact therapeutic strategies.
Highlights
The volume fraction of red blood cells in blood, hematocrit (Hct), can be measured during a simple blood test and serves as an indicator of health status
To validate this new approach, tissue Hct (tHct) was mapped in the rat brain under physiological conditions as well as following a decrease in systemic Hct or following an increase in systemic Hct (erythropoietin (EPO) injection)
Despite the fact that the proposed approach appears slightly noisier than the reference capillary methods, these results highlights the ability of dual-isotope autoradiography to obtain accurate estimates of blood hematocrit (bHct)
Summary
The volume fraction of red blood cells in blood, hematocrit (Hct), can be measured during a simple blood test and serves as an indicator of health status. While change in systemic Hct are known to impact stroke[6] or tumor control[7], intralesional Hct heterogeneity induced by these diseases have received little attention In preclinical studies, this lack of interest may originate from a lack of available method to map tHct in a single animal. Due to the low sensitivity of x-ray films, long half-life isotopes such as 131I (half-life: 8.0 days) or 125I (59.4 days) for the albumin and 51Cr (27.7 days), 59Fe (44.5 days) or 55Fe (2.7 years) for RBC were employed, thereby allowing long exposure times of several weeks With these long half-life isotopes, Vp and Vrbc had to be obtained on separated groups of animals, and average tHct were derived in a given brain structure. We propose a new approach to map the tHct across the brain: a dual isotope autoradiography, using 125I-labeled albumin (59.4 days half-life) and 99mTc-labeled RBC (6 hours half-life). We evaluated the change of local Hct in rat models of tumor (two glioma models) and of stroke (middle cerebral artery occlusion)
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