Background In response to the inflammatory reaction, circulating leukocytes aggregate and adhere to the endothelial cells and eventually pervade into tissues, resulting in cell damage. This study was to detect the in...Background In response to the inflammatory reaction, circulating leukocytes aggregate and adhere to the endothelial cells and eventually pervade into tissues, resulting in cell damage. This study was to detect the inflammatory reactions in mouse focal cerebral ischemia and their distinct characteristics in the ischemic basal ganglia and surrounding cortex.Methods Mice were subjected to permanent occlusion of the left middle cerebral artery (MCAO) by introducing a suture for 2 to 120 hours. The expression of intercellular adhesion molecule 1 (ICAM-1) and Mac-1 was determined immunohistochemically. The myeloperoxidase (MPO) activity of the ischemic regions was measured.Results Four hours after MCAO, the number of ICAM-1 positive vessels in the ischemic basal ganglia increased (9.2±2.8 per mm 2), peaked at 48 hours (29.6±4.8 per mm 2), and decreased after 72 hours. In the ischemic cortex, the number increased rapidly 4 hours after MCAO (19.4±6.1 per mm 2), peaked at 48 hours (44.4±16.8 per mm 2), and declined after 72 hours. Mac-1 positive cells were seen in the ischemic basal ganglia (3.4±1.2 per mm 2) 12 hours after MCAO, peaked after 48 hours (20.2±6.3 per mm 2), and decreased after 72 hours. In the ischemic cortex, however, the number increased 4 hours after MCAO (4.3±1.7 per mm 2), peaked after 48 hours (20.9±8.4 per mm 2), and remained high at 120 hours. The MPO activity increased in the ischemic basal ganglia 12 hours after MCAO (0.111±0.023 U/g), peaked after 24 hours (0.194±0.059 U/g), and decreased after 72 hours. In the ischemic cortex, the MPO activity increased 12 hours after MCAO (0.110±0.032 U/g), peaked after 24 hours (0.210±0.067 U/g), and remained elevated at 120 hours.Conclusions The increased expression of ICAM-1 in the ischemic brain of mouse in the early phase of MCAO followed by the over-expression of Mac-1 and the increased MPO activity suggests that focal ischemia leads to early onset of inflammation. The inflammatory response is more persistent and inte展开更多
Objective To determine the role of extracellular signal-regulated kinase (ERK)1/2 during focal cerebral ischemia.Methods Left middle cerebral artery occlusion (MCAO) was undergone after the introduction of a nylon sut...Objective To determine the role of extracellular signal-regulated kinase (ERK)1/2 during focal cerebral ischemia.Methods Left middle cerebral artery occlusion (MCAO) was undergone after the introduction of a nylon suture to the left internal carotid artery in 70 male adult CD-1 mice. ERK 1/2 phosphorylation was detected using Western blot analysis,and the morphological feature was determined by immunohistochemistry. An ERK pathway inhibitor,1,4-diamino-2,3-dicyano-1,4-bis[2-amino-phenylthio] butadiene (U0126),was administered intravenously 20 minutes before MCAO,and the neurological deficit levels and the infarct volumes were measured 24 hours after MCAO.Results Phosphorylated ERK 1/2 (pERK 1/2) activity increased after 30 minutes of MCAO and peaked at 2 hours. The immunohistochemical study displayed a large number of pERK 1/2 positive cells in the ischemic basal ganglion and surrounding cortex. Double-labeled fluorescent staining identified the pERK1/2 positive cells as neurons or astrocytes. In U0126 treated mice which had undergone 24 hours of MCAO,the neurological deficit levels and the infarct volumes were 44.6% and 45.8% respectively,less than those of the control mice.Conclusions ERK plays an important role in focal cerebral ischemia and inhibition of the ERK pathway can help protect against ischemic brain injury,which may provide a therapeutic approach for cerebral ischemia.展开更多
Objective To establish a mouse model of middle cerebral artery occlusion, which mimics focal ischemia in humans and to demonstrate the advantages and disadvantages of the model Methods CD 1 mice (n=126) had perman...Objective To establish a mouse model of middle cerebral artery occlusion, which mimics focal ischemia in humans and to demonstrate the advantages and disadvantages of the model Methods CD 1 mice (n=126) had permanent middle cerebral artery occlusion for 24?h, or temporary occlusion for either one hour followed by 23?h of reperfusion or 2?h of occlusion with 22?h of reperfusion The middle cerebral artery was occluded by insertion of a suture through the internal carotid artery Reperfusion was established by suture withdrawal The degree of occlusion and the extent of reperfusion were determined using laser Doppler Infarct volume was measured with 2, 3, 5 triphenyl tetrazolium chloride staining, and the blood brain barrier disruption was demonstrated using albumin immunohistochemistry Results Blood flow decreased to 14%-19% of baseline in both the permanent and temporary occlusion groups and was restored to 51%-75% of baseline after reperfusion The infarct volume was smaller in the 1?h/23?h temporary occlusion group ( P <0 05) than in either the 24?h permanent occlusion group or the 2?h/22?h temporary occlusion group Blood brain barrier disruption was also smaller in the 1?h/23?h temporary occlusion group than in either the 24?h permanent occlusion or the 2?h/22?h temporary occlusion group ( P <0 05) Conclusion Permanent or temporary middle cerebral artery occlusion causes reproducible brain injury in the mouse Blood brain barrier disruption and infarct volume remain important markers of focal cerebral ischemia展开更多
文摘Background In response to the inflammatory reaction, circulating leukocytes aggregate and adhere to the endothelial cells and eventually pervade into tissues, resulting in cell damage. This study was to detect the inflammatory reactions in mouse focal cerebral ischemia and their distinct characteristics in the ischemic basal ganglia and surrounding cortex.Methods Mice were subjected to permanent occlusion of the left middle cerebral artery (MCAO) by introducing a suture for 2 to 120 hours. The expression of intercellular adhesion molecule 1 (ICAM-1) and Mac-1 was determined immunohistochemically. The myeloperoxidase (MPO) activity of the ischemic regions was measured.Results Four hours after MCAO, the number of ICAM-1 positive vessels in the ischemic basal ganglia increased (9.2±2.8 per mm 2), peaked at 48 hours (29.6±4.8 per mm 2), and decreased after 72 hours. In the ischemic cortex, the number increased rapidly 4 hours after MCAO (19.4±6.1 per mm 2), peaked at 48 hours (44.4±16.8 per mm 2), and declined after 72 hours. Mac-1 positive cells were seen in the ischemic basal ganglia (3.4±1.2 per mm 2) 12 hours after MCAO, peaked after 48 hours (20.2±6.3 per mm 2), and decreased after 72 hours. In the ischemic cortex, however, the number increased 4 hours after MCAO (4.3±1.7 per mm 2), peaked after 48 hours (20.9±8.4 per mm 2), and remained high at 120 hours. The MPO activity increased in the ischemic basal ganglia 12 hours after MCAO (0.111±0.023 U/g), peaked after 24 hours (0.194±0.059 U/g), and decreased after 72 hours. In the ischemic cortex, the MPO activity increased 12 hours after MCAO (0.110±0.032 U/g), peaked after 24 hours (0.210±0.067 U/g), and remained elevated at 120 hours.Conclusions The increased expression of ICAM-1 in the ischemic brain of mouse in the early phase of MCAO followed by the over-expression of Mac-1 and the increased MPO activity suggests that focal ischemia leads to early onset of inflammation. The inflammatory response is more persistent and inte
文摘Objective To determine the role of extracellular signal-regulated kinase (ERK)1/2 during focal cerebral ischemia.Methods Left middle cerebral artery occlusion (MCAO) was undergone after the introduction of a nylon suture to the left internal carotid artery in 70 male adult CD-1 mice. ERK 1/2 phosphorylation was detected using Western blot analysis,and the morphological feature was determined by immunohistochemistry. An ERK pathway inhibitor,1,4-diamino-2,3-dicyano-1,4-bis[2-amino-phenylthio] butadiene (U0126),was administered intravenously 20 minutes before MCAO,and the neurological deficit levels and the infarct volumes were measured 24 hours after MCAO.Results Phosphorylated ERK 1/2 (pERK 1/2) activity increased after 30 minutes of MCAO and peaked at 2 hours. The immunohistochemical study displayed a large number of pERK 1/2 positive cells in the ischemic basal ganglion and surrounding cortex. Double-labeled fluorescent staining identified the pERK1/2 positive cells as neurons or astrocytes. In U0126 treated mice which had undergone 24 hours of MCAO,the neurological deficit levels and the infarct volumes were 44.6% and 45.8% respectively,less than those of the control mice.Conclusions ERK plays an important role in focal cerebral ischemia and inhibition of the ERK pathway can help protect against ischemic brain injury,which may provide a therapeutic approach for cerebral ischemia.
文摘Objective To establish a mouse model of middle cerebral artery occlusion, which mimics focal ischemia in humans and to demonstrate the advantages and disadvantages of the model Methods CD 1 mice (n=126) had permanent middle cerebral artery occlusion for 24?h, or temporary occlusion for either one hour followed by 23?h of reperfusion or 2?h of occlusion with 22?h of reperfusion The middle cerebral artery was occluded by insertion of a suture through the internal carotid artery Reperfusion was established by suture withdrawal The degree of occlusion and the extent of reperfusion were determined using laser Doppler Infarct volume was measured with 2, 3, 5 triphenyl tetrazolium chloride staining, and the blood brain barrier disruption was demonstrated using albumin immunohistochemistry Results Blood flow decreased to 14%-19% of baseline in both the permanent and temporary occlusion groups and was restored to 51%-75% of baseline after reperfusion The infarct volume was smaller in the 1?h/23?h temporary occlusion group ( P <0 05) than in either the 24?h permanent occlusion group or the 2?h/22?h temporary occlusion group Blood brain barrier disruption was also smaller in the 1?h/23?h temporary occlusion group than in either the 24?h permanent occlusion or the 2?h/22?h temporary occlusion group ( P <0 05) Conclusion Permanent or temporary middle cerebral artery occlusion causes reproducible brain injury in the mouse Blood brain barrier disruption and infarct volume remain important markers of focal cerebral ischemia
