K⁺ dynamics in ischemic rat brain in vivo by ⁸⁷Rb MRI at 7 T

Abstract

The aims of the present study were 1) to perform the first 87Rb MRI in live rats with a focal ischemic stroke; and 2) to test the hypothesis that K+ egress from the brain in this model is quantifiable in individual animals by the high field (7 T) K/Rb substitution MRI. Rats pre-loaded with dietary Rb+ (resulting in replacement ratios Rb/(K+Rb) of 0.1 to 0.2 in the brain) were subjected to permanent occlusion of the middle cerebral artery, and 87Rb MRI was implemented with 13-min temporal resolution using a dedicated radiofrequency coil and a spiral ultrashort-TE sequence (TR/TE of 3/0.07 ms). The ischemic core was localized by apparent diffusion coefficient mapping, by microtubule-associated protein-2 immunohistochemistry, and by changes in surface reflectivity. [K], [Na] and [Rb] were independently determined in the micropunched samples by post-mortem flame photometry. Both techniques were generally in agreement in the non-ischemic cortex, however, the MRI-assessed [K++Rb+] drop in ischemic brain was less pronounced (average efflux rate of 4.8 ± 0.2 nEq/mm3/h, vs. 10 ± 1 nEq/mm3/h by flame photometry, P < 0.0001). The use of higher field gradients for better spatial resolution and, hence, more accurate quantitation, is suggested.

Increased glucose availability does not restore prolonged spreading depression durations in hypotensive rats without brain injury

“…Such systems are indeed present on the abluminal membranes of cerebrovascular endothelium (Bradbury et al 1972; Goldstein 1979). In support of this, a net loss of total brain tissue K + has been demonstrated after anoxic depolarization with permanent [K + ] e elevations comparable to CSD (Hu et al 2000; Yushmanov et al 2011). Although vascular clearance is an attractive hypothesis to explain delayed CSD recovery during reduced cerebral perfusion pressure, direct evidence in support of such a mechanism is still lacking.…”

Rubidium and potassium levels are altered in Alzheimer’s disease brain and blood but not in cerebrospinal fluid

“…T 1 and T 2 relaxation times are well suited to magnetic resonance imaging using specialized coils, and this approach has been used to quantitatively assess K (using 87 Rb as a proxy) in the brains of ischemic rats [42, 43]. This approach uses chronic Rb loading via drinking water in the weeks preceding MRI scanning, which could be employed in a diagnostic workflow for AD, though the use of high field strength (e.g., 7 T) MRI systems may have the capacity to assess endogenous 87 Rb with sufficient sensitivity.…”

Correlated sodium and potassium imbalances within the ischemic core in experimental stroke: A 23Na MRI and histochemical imaging study

“…For quantitative comparison, [Na + ] br and [K + ] br maps were obtained by 23 Na MRI and histochemical K + staining, respectively, and calibrated by emission flame photometry of the micropunch brain samples. Histochemical staining provided higher spatial resolution and more precise quantitation of [K + ] br (albeit only post mortem) in comparison with 87 Rb MRI (Yushmanov et al, 2011). Stroke presence and location was verified by MRI of the apparent diffusion coefficient (ADC), by changes in surface reflectivity of ischemic tissue, and by immunohistochemistry with microtubule-associated protein 2 (MAP2) antibody, as shown in Fig.…”

“…This suggests the difference in pathophysiologic processes between the center and periphery of the infarct core and attests to the role of collateral circulation in the edge regions. Further refinement of the ion dynamics in peripheral ischemic core will take advantage of 87 Rb MRI in vivo for the study of the time course of [K + ] br in individual ischemic brain (Yushmanov et al, 2007; Yushmanov et al, 2011). Better understanding of the mechanistic link between the Na + influx and K + egress would validate the 23 Na MRI slope as a candidate biomarker and a complementary tool for assessing ischemic damage and treatment planning.…”

“…An increase in brain tissue sodium concentration ([Na + ] br ) after stroke, as well as a concomitant drop in potassium brain concentration ([K + ] br ), were well documented by brain sampling in animal models (Betz et al, 1994; Ito et al, 1979; Schuier and Hossmann, 1980; Shibata et al, 1974). Further refinement of brain sampling techniques enabled rapid measurements of [Na + ] br and [K + ] br locally even in small rodent brains (Yushmanov et al, 2007; Yushmanov et al, 2011). Recently, [Na + ] br has been considered as a potential biomarker for brain tissue viability after stroke (Boada et al, 2012; Thulborn et al, 1999), as well as a tool to determine the stroke onset time and establish patient eligibility for thrombolytic therapy (Jones et al, 2006).…”