Evolution of microglial activation in patients after ischemic stroke: a [11C](R)-PK11195 PET study

We obtained [11C](R)-PK11195 PET scans in six patients at different time points between 3 and 150 days after onset of ischemic stroke in order to measure the time course of microglial activation. Increased [11C](R)-PK11195 binding around the lesion was observed as early as 3 days. Scans at later time points showed ongoing changes in the distribution of the [11C](R)-PK11195 signal, involving the area of the primary lesion and areas distant from the primary lesion site. Our data suggest that [11C](R)-PK11195 PET can be used to investigate both the primary lesion and remote pathological changes following Wallerian degeneration.

[1]  Jean-Claude Baron,et al.  In Vivo Mapping of Brain Benzodiazepine Receptor Changes by Positron Emission Tomography After Focal Ischemia in the Anesthetized Baboon , 1993, Stroke.

[2]  T. Spinks,et al.  Physical characteristics of the ECAT EXACT3D positron tomograph. , 2000, Physics in medicine and biology.

[3]  R B Banati,et al.  In vivo visualization of activated glia by [11C] (R)-PK11195-PET following herpes encephalitis reveals projected neuronal damage beyond the primary focal lesion. , 2001, Brain : a journal of neurology.

[4]  R. Dempsey,et al.  Up‐regulation of the peripheral‐type benzodiazepine receptor expression and [3H]PK11195 binding in gerbil hippocampus after transient forebrain ischemia , 2001, Journal of neuroscience research.

[5]  M. Moskowitz,et al.  Pathobiology of ischaemic stroke: an integrated view , 1999, Trends in Neurosciences.

[6]  R. Banati.  Brain plasticity and microglia: is transsynaptic glial activation in the thalamus after limb denervation linked to cortical plasticity and central sensitisation? , 2002, Journal of Physiology-Paris.

[7]  G Brix,et al.  Performance evaluation of a whole-body PET scanner using the NEMA protocol. National Electrical Manufacturers Association. , 1997, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[8]  R Tomczak,et al.  In vivo imaging of activated microglia using [11 C]PK11195 and positron emission tomography in patients after ischemic stroke , 2000, Neuroreport.

[9]  D L Hill,et al.  Automated three-dimensional registration of magnetic resonance and positron emission tomography brain images by multiresolution optimization of voxel similarity measures. , 1997, Medical physics.

[10]  F E Turkheimer,et al.  [11C](R)-PK11195 positron emission tomography imaging of activated microglia in vivo in Rasmussen’s encephalitis , 1999, Neurology.

[11]  D Comar,et al.  "Crossed cerebellar diaschisis" in human supratentorial brain infarction. , 1981, Transactions of the American Neurological Association.

[12]  D. Duverger,et al.  Imaging of primary and remote ischaemic and excitotoxic brain lesions. An autoradiographic study of peripheral type benzodiazepine binding sites in the rat and cat , 1988, Brain Research.

[13]  Ulrich Dirnagl,et al.  Selective Neuronal Vulnerability Following Mild Focal Brain Ischemia in the Mouse , 2003, Brain pathology.

[14]  R B Banati,et al.  [11C](R)-PK11195 PET imaging of microglial activation in multiple system atrophy , 2003, Neurology.

[15]  M. Graeber,et al.  Surveillance, intervention and cytotoxicity: is there a protective role of microglia? , 1994, Developmental neuroscience.

[16]  F. Turkheimer,et al.  Towards a transcriptome definition of microglial cells , 2004, Neurogenetics.

[17]  R B Banati,et al.  Thalamic microglial activation in ischemic stroke detected in vivo by PET and [11C]PK11195 , 2000, Neurology.

[18]  R B Banati,et al.  The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity. , 2000, Brain : a journal of neurology.

[19]  R. Frackowiak,et al.  Monitoring by PET of macrophage accumulation in brain after ischaemic stroke , 1992, The Lancet.

[20]  Vincent J. Cunningham,et al.  Parametric Imaging of Ligand-Receptor Binding in PET Using a Simplified Reference Region Model , 1997, NeuroImage.

[21]  J. Zimmer,et al.  Microglial and macrophage reactions mark progressive changes and define the penumbra in the rat neocortex and striatum after transient middle cerebral artery occlusion , 1997 .

[22]  Roger N Gunn,et al.  In-vivo measurement of activated microglia in dementia , 2001, The Lancet.

[23]  Richard S. J. Frackowiak,et al.  [3H]PK 11195 and the localisation of secondary thalamic lesions following focal ischaemia in rat motor cortex , 1991, Neuroscience Letters.