PMC:4627622 / 21804-24412 JSONTXT

{"project":"TEST0","denotations":[{"id":"26512021-234-240-1479100","span":{"begin":765,"end":767},"obj":"[\"9463456\"]"},{"id":"26512021-235-241-1479101","span":{"begin":769,"end":771},"obj":"[\"26329487\"]"},{"id":"26512021-230-236-1479102","span":{"begin":773,"end":775},"obj":"[\"8955268\"]"},{"id":"26512021-234-240-1479103","span":{"begin":777,"end":779},"obj":"[\"22652383\"]"},{"id":"26512021-235-241-1479104","span":{"begin":781,"end":783},"obj":"[\"14705109\"]"},{"id":"26512021-105-111-1479105","span":{"begin":891,"end":893},"obj":"[\"8395298\"]"},{"id":"26512021-105-111-1479106","span":{"begin":1146,"end":1148},"obj":"[\"9463456\"]"},{"id":"26512021-115-121-1479107","span":{"begin":1408,"end":1410},"obj":"[\"15146242\"]"},{"id":"26512021-225-231-1479108","span":{"begin":1728,"end":1730},"obj":"[\"1381261\"]"},{"id":"26512021-110-115-1479109","span":{"begin":1843,"end":1844},"obj":"[\"18727638\"]"},{"id":"26512021-86-92-1479110","span":{"begin":2370,"end":2372},"obj":"[\"3694267\"]"},{"id":"26512021-226-232-1479111","span":{"begin":2601,"end":2603},"obj":"[\"9450765\", \"10570723\", \"15839846\"]"}],"text":"Permeability of TG/CNS in relation to BBB\nThe results presented here, show that permeability was significantly higher in the TG than in other structures analysed (Fig. 2), both after addition of vehicle and after application of CFA or IS. This illustrates that the drug-availability will be much higher in the TG compared to the CNS and supports this as a potential target for anti-migraine drugs [9]. The inflammatory model has been utilized in several studies and show similar findings to migraine for example TG activation with an increase in p-ERK1/2 activation and IL-1β expression, hypersensitivity to mechanical and thermal stimulation, as well as activation in the TG and in the brain stem trigeminal neurons, similar to what could be expected in migraine [17, 24, 29, 36, 37]. Since it has been suggested that the BBB in migraine patients might be defective or transiently altered [12], we tested if the BBB was altered in the present method. Obviously this is not a “true” migraine model; it may be regarded as a surrogate method. IS has been used in many studies for the understanding of for example trigeminal involved sensitization [17]. CFA is a well-known method to induce local inflammation and we postulate that this may share aspects with the more chronic forms of migraine. In relation to other models, there exists one study on repeated cortical spreading depression and the BBB in rats [25]. Here a mild BBB breakdown/leakage was observed including brain edema and protein leakage. However, the cortical depression has to be very strong for these effects, for example after cerebral ischemia where there is a strong cortical spreading depression, it still takes several hours for the BBB to be broken down [38]. In addition, there are no clear proof of breakdown or leakage in the BBB in patients during migraine attacks [8]\nInterestingly, in a study by Markowitz and colleagues, extravasated 125I-BSA or Evans blue was noted in the dura of saline-perfused rats following intravenous capsaicin or following electrical stimulation of the rat TG. Extravasation was however not observed in the brain following chemical, electrical, or immunological stimulation nor following topical application of capsaicin to the pial surface or injection into the cortex of rats. The data are therefore showing similar indication as us, with our inflammatory model [39]. As we did not observe any alteration in the BBB, we add our data to the negative experiments that the BBB does not change its permeability during migraine attacks. Our results are in agreement with clinical data observations [26–28]."}

{"project":"2_test","denotations":[{"id":"26512021-9463456-60534742","span":{"begin":765,"end":767},"obj":"9463456"},{"id":"26512021-26329487-60534743","span":{"begin":769,"end":771},"obj":"26329487"},{"id":"26512021-8955268-60534744","span":{"begin":773,"end":775},"obj":"8955268"},{"id":"26512021-22652383-60534745","span":{"begin":777,"end":779},"obj":"22652383"},{"id":"26512021-14705109-60534746","span":{"begin":781,"end":783},"obj":"14705109"},{"id":"26512021-8395298-60534747","span":{"begin":891,"end":893},"obj":"8395298"},{"id":"26512021-9463456-60534748","span":{"begin":1146,"end":1148},"obj":"9463456"},{"id":"26512021-15146242-60534749","span":{"begin":1408,"end":1410},"obj":"15146242"},{"id":"26512021-1381261-60534750","span":{"begin":1728,"end":1730},"obj":"1381261"},{"id":"26512021-18727638-60534751","span":{"begin":1843,"end":1844},"obj":"18727638"},{"id":"26512021-3694267-60534752","span":{"begin":2370,"end":2372},"obj":"3694267"},{"id":"26512021-9450765-60534753","span":{"begin":2601,"end":2603},"obj":"9450765"},{"id":"26512021-10570723-60534753","span":{"begin":2601,"end":2603},"obj":"10570723"},{"id":"26512021-15839846-60534753","span":{"begin":2601,"end":2603},"obj":"15839846"}],"text":"Permeability of TG/CNS in relation to BBB\nThe results presented here, show that permeability was significantly higher in the TG than in other structures analysed (Fig. 2), both after addition of vehicle and after application of CFA or IS. This illustrates that the drug-availability will be much higher in the TG compared to the CNS and supports this as a potential target for anti-migraine drugs [9]. The inflammatory model has been utilized in several studies and show similar findings to migraine for example TG activation with an increase in p-ERK1/2 activation and IL-1β expression, hypersensitivity to mechanical and thermal stimulation, as well as activation in the TG and in the brain stem trigeminal neurons, similar to what could be expected in migraine [17, 24, 29, 36, 37]. Since it has been suggested that the BBB in migraine patients might be defective or transiently altered [12], we tested if the BBB was altered in the present method. Obviously this is not a “true” migraine model; it may be regarded as a surrogate method. IS has been used in many studies for the understanding of for example trigeminal involved sensitization [17]. CFA is a well-known method to induce local inflammation and we postulate that this may share aspects with the more chronic forms of migraine. In relation to other models, there exists one study on repeated cortical spreading depression and the BBB in rats [25]. Here a mild BBB breakdown/leakage was observed including brain edema and protein leakage. However, the cortical depression has to be very strong for these effects, for example after cerebral ischemia where there is a strong cortical spreading depression, it still takes several hours for the BBB to be broken down [38]. In addition, there are no clear proof of breakdown or leakage in the BBB in patients during migraine attacks [8]\nInterestingly, in a study by Markowitz and colleagues, extravasated 125I-BSA or Evans blue was noted in the dura of saline-perfused rats following intravenous capsaicin or following electrical stimulation of the rat TG. Extravasation was however not observed in the brain following chemical, electrical, or immunological stimulation nor following topical application of capsaicin to the pial surface or injection into the cortex of rats. The data are therefore showing similar indication as us, with our inflammatory model [39]. As we did not observe any alteration in the BBB, we add our data to the negative experiments that the BBB does not change its permeability during migraine attacks. Our results are in agreement with clinical data observations [26–28]."}