Intrinsic Activated Microglia Map to the Peri-infarct Zone in the Subacute Phase of Ischemic Stroke
| Autor: | Franklin I. Aigbirhio, David K. Menon, Jean-Claude Baron, Joe V. Guadagno, Dechao Wang, Tim D. Fryer, Marcel C. Cleij, Christopher J. Price, Elizabeth A. Warburton |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Adult
Male Cerebellum Pathology medicine.medical_specialty Time Factors Infarction Nerve Tissue Proteins Brain Ischemia Central nervous system disease Receptors GABA medicine Humans Carbon Radioisotopes Stroke Aged Advanced and Specialized Nursing medicine.diagnostic_test Cerebral infarction business.industry Binding potential Infarction Middle Cerebral Artery Isoquinolines medicine.disease Peripheral medicine.anatomical_structure Positron emission tomography Positron-Emission Tomography Acute Disease Female Microglia Neurology (clinical) Radiopharmaceuticals Cardiology and Cardiovascular Medicine business Protein Binding |
| Zdroj: | Stroke. 37:1749-1753 |
| ISSN: | 1524-4628 0039-2499 |
| DOI: | 10.1161/01.str.0000226980.95389.0b |
| Popis: | Background and Purpose— Microglial activation is an important component of the neuroinflammatory response to ischemic stroke. Experimental studies have outlined such patterns temporally and spatially. In vivo studies in stroke patients have relied on positron emission tomography and (R)-PK11195, a ligand that binds peripheral benzodiazepine binding sites. In this study we sought to establish temporal and spatial patterns of microglial activation in ischemic stroke with particular emphasis on a defined peri-infarct zone. Methods— Using this technique, we studied carotid territory ischemic stroke patients in 3 time windows up to 30 days after ictus. Controls were studied in a single session. [ 11 C](R)-PK11195 injection was followed by 3-dimensional acquisition over 60 minutes. Cerebral blood volume (CBV) was measured afterward with the use of standard C 15 O paradigms. Analysis employed the reference tissue model in which ipsilateral cerebellum was used to generate parametric binding potential maps corrected for CBV. Data were coregistered to T1-based MRI. Using control data to identify 99% confidence limits, a region of interest analysis was applied to identify significant binding in core infarction, contralateral hemisphere, and within a defined peri-infarct zone. Results— Four patients (mean age, 66 years) were imaged across 9 sessions. Four age-matched controls were studied. Within this model, ipsilateral cerebellum was validated as a reference tissue. With the use of control-derived confidence limits and correction for CBV, significant binding potential rises were identified beyond 72 hours and extending to 30 days in core infarction, contralateral hemisphere, and peri-infarct zone. Conclusions— In ischemic stroke patients, minimal activation of microglia is seen before 72 hours. Beyond this, binding potential rises in core infarction, peri-infarct zone, and contralateral hemisphere to 30 days. This may represent a therapeutic opportunity that extends beyond time windows traditionally reserved for neuroprotection. |
| Databáze: | OpenAIRE |
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