Multimodal imaging reveals temporal and spatial microglia and matrix metalloproteinase activity after experimental stroke

多模态成像揭示实验性中风后时间和空间的小胶质细胞和基质金属蛋白酶活性

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作者:Bastian Zinnhardt, Thomas Viel, Lydia Wachsmuth, Alexis Vrachimis, Stefan Wagner, Hans-Jörg Breyholz, Andreas Faust, Sven Hermann, Klaus Kopka, Cornelius Faber, Frédéric Dollé, Sabina Pappata, Anna M Planas, Bertrand Tavitian, Michael Schäfers, Lydia M Sorokin, Michael T Kuhlmann, Andreas H Jacobs

Abstract

Stroke is the most common cause of death and disability from neurologic disease in humans. Activation of microglia and matrix metalloproteinases (MMPs) is involved in positively and negatively affecting stroke outcome. Novel, noninvasive, multimodal imaging methods visualizing microglial and MMP alterations were employed. The spatio-temporal dynamics of these parameters were studied in relation to blood flow changes. Micro positron emission tomography (μPET) using [(18)F]BR-351 showed MMP activity within the first days after transient middle cerebral artery occlusion (tMCAo), followed by increased [(18)F]DPA-714 uptake as a marker for microglia activation with a maximum at 14 days after tMCAo. The inflammatory response was spatially located in the infarct core and in adjacent (penumbral) tissue. For the first time, multimodal imaging based on PET, single photon emission computed tomography, and magnetic resonance imaging revealed insight into the spatio-temporal distribution of critical parameters of poststroke inflammation. This allows further evaluation of novel treatment paradigms targeting the postischemic inflammation.

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