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Thromboembolic stroke in C57BL/6 mice monitored by 9.4 T MRI using a 1H cryo probe

DOI: 10.1186/2040-7378-4-18

Keywords: Embolic stroke, Experimental, T-PA, MRI, Animal models

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Abstract:

Clot formation was triggered by microinjection of murine thrombin into the right middle cerebral artery (MCA). Animals (n?=?28) were treated with 10?mg/kg, 5?mg/kg or no tissue plasminogen activator (t-PA) 40?min after MCA occlusion. For MR-imaging a Bruker 9.4?T animal system with a 1H surface cryo probe was used and a T2-weighted RARE sequence, a diffusion weighted multishot EPI sequence and a 3D flow-compensated gradient echo TOF angiography were performed.The infarct volume in animals treated with t-PA was significantly reduced (0.67?±?1.38?mm3 for 10?mg/kg and 10.9?±?8.79?mm3 for 5?mg/kg vs. 19.76?±?2.72?mm3 ; p?<?0.001) compared to untreated mice. An additional group was reperfused with t-PA inside the MRI. Already ten minutes after beginning of t-PA treatment, reperfusion flow was re-established in the right MCA. However, signal intensity was lower than in the contralateral MCA. This reduction in cerebral blood flow was attenuated during the first 60?minutes after reperfusion. 24?h after MCA occlusion and reperfusion, no difference in signal intensity of the contralateral and ipsilateral MCAs was observed.We confirm a t-Pa effect using this stroke model in the C57BL76 mouse strain and demonstrate a chronological sequence MRI imaging after t-PA using a 1H surface cryo coil in a 9.4?T MRI. This setting will allow testing of new thrombolytic strategies for stroke treatment in-vivo in C57BL76 knock-out mice.Approximately 75% of all stroke subtypes are caused by embolism leading to cerebral vessel occlusion [1]. The only approved specific treatment for acute stroke is thrombolysis with tissue plasminogen activator (t-PA), which restores cerebral blood flow and improves the neurological outcome in patients with acute ischaemic stroke. This therapy however is associated with certain risks, such as secondary haemorrhage after stroke. New treatment strategies are therefore required, rendering the development of new animal models in combination with adequate imaging st

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