Browsing by Author "Pitkonen M."

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    The blood-brain barrier is continuously open for several weeks following transient focal cerebral ischemia
    (2008) Strbian D.; Durukan A.; Pitkonen M.; Marinkovic I.; Tatlisumak E.; Pedrono E.; Abo-Ramadan U.; Tatlisumak T.
    The blood-brain barrier (BBB) is the principal regulator of blood-borne substance entry into the brain parenchyma. Therefore, BBB leakage, which leads to cerebral edema and influx of toxic substances, is common in pathological conditions such as cerebral ischemia, inflammation, trauma, and tumors. The leakage of BBB after ischemia-reperfusion injury has long been considered to be biphasic, although a considerable amount of discrepancies as for the timing of the second opening does exist among the studies. This led us to evaluate systematically and quantitatively the dynamics of BBB leakage in a rat model of 90-min ischemia-reperfusion, using gadolinium-enhanced (small molecule) magnetic resonance imaging and fluorescent dye Evans Blue (large molecule). BBB leakage was assessed at the following time points after reperfusion: 25 min, 2, 4, 6, 12, 18, 24, 36, 48, and 72 h, and 1, 2, 3, 4, and 5 weeks. We observed BBB leakage for both gadolinium and Evans Blue as early as 25 min after reperfusion. Thereafter, BBB remained open for up to 3 weeks for Evans Blue and up to 5 weeks for gadolinium. Our results show that BBB leakage after ischemia-reperfusion injury in the rat is continuous and long-lasting, without any closure up to several weeks. This is the first systematic and extensive study fully demonstrating BBB leakage dynamics following transient brain ischemia and the findings are of major clinical and experimental interest. © 2008 IBRO.
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    Post-ischemic leakiness of the blood-brain barrier: A quantitative and systematic assessment by Patlak plots
    (2009) Abo-Ramadan U.; Durukan A.; Pitkonen M.; Marinkovic I.; Tatlisumak E.; Pedrono E.; Soinne L.; Strbian D.; Tatlisumak T.
    The Patlak plot analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows estimation of blood-brain barrier (BBB) leakage following temporary focal cerebral ischemia. Thus far, a systematic and quantitative in vivo evaluation of post-ischemic BBB leakage is lacking. Here, using DCE-MRI and the Patlak plot method, we quantitatively assessed BBB leakage in rats at the following time-points after reperfusion: 25 min, 2, 4, 6, 12, 18, 24, 36, 48, and 72 h, and 1, 2, 3, 4, and 5 weeks. Sham-operated animals served as controls. Data collected for each time-point were: the blood-to-brain transfer rate constant (Ki) of the contrast agent gadolinium, distribution volume (Vp), ischemic lesion volume, and apparent diffusion coefficient (ADC) values. Compared to controls, Ki, measured at all time-points, except for 5 weeks, appeared significantly different (p < 0.001). At several time-points (25 min, 48 and 72 h, 4 and 5 weeks), Vp was similar compared to that of controls, but for the remaining groups the difference was significant (p < 0.001). Analyzing the relationship of Ki values to time-points, we observed a trend towards a decrease over time (r = - 0.61, p = 0.014). Both ADC values (r = - 0.58, p = 0.02) and ischemic lesion volumes (r = 0.75, p = 0.0015) correlated with Ki values. These results suggest that after ischemia-reperfusion in rats, BBB leakage is continuous during a 4-week period. Its magnitude diminishes over time and correlates with severity and extent of ischemic injury. © 2009 Elsevier Inc. All rights reserved.