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

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.

• Authors: 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
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 35 Issue 11 Pg. 1711-21 (Nov 2015) ISSN: 1559-7016 [Electronic] United States
• PMID: 26126867 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide
• Pyrazoles
• Pyrimidines
• Radiopharmaceuticals
• Technetium Tc 99m Exametazime
• Matrix Metalloproteinases

Topics

• Animals
• Immunohistochemistry
• Infarction, Middle Cerebral Artery (diagnostic imaging, metabolism)
• Magnetic Resonance Imaging
• Matrix Metalloproteinases (metabolism)
• Mice
• Mice, Inbred C57BL
• Microglia (diagnostic imaging, pathology)
• Multimodal Imaging (methods)
• Neuroimaging (methods)
• Positron-Emission Tomography
• Pyrazoles
• Pyrimidines
• Radiopharmaceuticals
• Stroke (diagnostic imaging, enzymology, pathology)
• Technetium Tc 99m Exametazime
• Tomography, Emission-Computed, Single-Photon