Brain tissue sodium is a ticking clock telling time after arterial occlusion in rat focal cerebral ischemia

Background and Purpose-Many patients with acute stroke are excluded from re ceiving thrombolysis agents within the necessary time limit (3 or 6 hours f rom stroke onset) because they or their family members are unable provide t he time of stroke onset. Brain tissue sodium concentration ([Na+]) increase s gradually and incessantly during the initial hours of experimental focal cerebral ischemia but only in severely damaged brain regions. We propose th at this steady increase in [Na+] can be used to estimate the time after art erial occlusion in the rat middle cerebral artery occlusion model of ischem ic stroke. Methods-Sixteen anesthetized Sprague-Dawley rats underwent permanent middle cerebral artery occlusion combined with bilateral common artery occlusion. After 100 to 450 minutes, diffusion-weighted MRI was used to generate appa rent diffusion coefficient (ADC) maps. cerebral blood flow (CBF) was determ ined with C-14-iodoanlipyrine tin a subset of 7 animals), and the brain was frozen. Autoradiographic CBF sections and punch samples for Na+ analysis w ere obtained from the brain at the same level of the MR image. Severely at risk regions were identified with an ADC of (520 mu m(2)/s and, in the subs et, with both ADC of <520 mu m(2)/s and CBF of <40 mL . 100 g(-1). min(-1). Results-Both CBF and the ADC dropped quickly and remained stable in the ini tial hours after ischemic onset. Linear regression revealed strong linearit y between [Na+] and time after onset, with a slope of 0.95 or 1.00 (mEq/kg DW)/min, with both ADC and ADC-plus-CBF criteria, respectively. The 95% CIs at 180 and 360 minutes were between 41 and 52 minutes. Conclusions-The time after ischemic onset can be estimated with this 2-step process. First, ADC and CBF are used to identify severely endangered regio ns. Second, the [Na+] in these regions is used to estimate time after onset . The favorable 95% CIs at the time limits for thrombolytic therapy and the availability of measurements of ADC, CBF, and [Na+] in humans through the use of MRI suggest that this time-estimation scheme could be used to assess the appropriateness of thrombolysis for patients who do nor know when the stroke occurred.