title: In vivo PET imaging of the α4β2 nicotinic acetylcholine receptor as a marker for brain inflammation after cerebral ischemia.
abstract: PET imaging of nicotinic acetylcholine receptors (nAChRs) could become an effective tool for the diagnosis and therapy evaluation of neurologic diseases. Despite this, the role of nAChRs α4β2 receptors after brain diseases such as cerebral ischemia and its involvement in inflammatory reaction is still largely unknown. To investigate this, we performed in parallel in vivo magnetic resonance imaging (MRI) and positron emission tomography (PET) with 2[(18)F]-fluoro-A85380 and [(11)C]PK11195 at 1, 3, 7, 14, 21, and 28 d after middle cerebral artery occlusion (MCAO) in rats. In the ischemic territory, PET with 2[(18)F]-fluoro-A85380 and [(11)C]PK11195 showed a progressive binding increase from days 3-7, followed by a progressive decrease from days 14-28 after cerebral ischemia onset. Ex vivo immunohistochemistry for the nicotinic α4β2 receptor and the mitochondrial translocator protein (18 kDa) (TSPO) confirmed the PET findings and demonstrated the overexpression of α4β2 receptors in both microglia/macrophages and astrocytes from days 7-28 after experimental ischemic stroke. Likewise, the role played by α4β2 receptors on neuroinflammation was supported by the increase of [(11)C]PK11195 binding in ischemic rats treated with the α4β2 antagonist dihydro-β-erythroidine hydrobromide (DHBE) at day 7 after MCAO. Finally, both functional and behavioral testing showed major impaired outcome at day 1 after ischemia onset, followed by a recovery of the sensorimotor function and dexterity from days 21-28 after experimental stroke. Together, these results suggest that the nicotinic α4β2 receptor could have a key role in the inflammatory reaction underlying cerebral ischemia in rats.
authors: Molecular Imaging Unit and amartin@cicbiomagune.es.
authors: Abraham
authors: A
authors: Martín
authors: Molecular Imaging Unit and.
authors: Boguslaw
authors: http://orcid.org/0000-0002-2098-1577
authors: B
authors: Szczupak
authors: Radiochemistry Department, Molecular Imaging Unit, CIC biomaGUNE, San Sebastián, Guipuzcoa, Spain.
authors: Vanessa
authors: V
authors: Gómez-Vallejo
authors: Department of Neurociences, University of the Basque Country, 48940 Leioa, Spain, Achucarro Basque Center for Neuroscience-UPV/EHU, 48170 Zamudio, Spain, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), 48940 Leioa, Spain, and.
authors: Maria
authors: M
authors: Domercq
authors: Molecular Imaging Unit and.
authors: Ainhoa
authors: A
authors: Cano
authors: Molecular Imaging Unit and.
authors: Daniel
authors: D
authors: Padro
authors: Molecular Imaging Unit and.
authors: Clara
authors: C
authors: Muñoz
authors: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors: Makoto
authors: M
authors: Higuchi
authors: Department of Neurociences, University of the Basque Country, 48940 Leioa, Spain, Achucarro Basque Center for Neuroscience-UPV/EHU, 48170 Zamudio, Spain, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), 48940 Leioa, Spain, and.
authors: Carlos
authors: C
authors: Matute
authors: Radiochemistry Department, Molecular Imaging Unit, CIC biomaGUNE, San Sebastián, Guipuzcoa, Spain.
authors: Jordi
authors: J
authors: Llop
mesh_terms: D000577:Amides; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D002452:Cell Count; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004660:Encephalitis / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000209:etiology*; D019788:Fluorodeoxyglucose F18; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000150:complications* / Q000000981:diagnostic imaging* / Q000473:pathology; D007546:Isoquinolines; D008279:Magnetic Resonance Imaging; D008297:Male; D001523:Mental Disorders / Q000209:etiology; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects; D011597:Psychomotor Performance; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013997:Time Factors
chemical_list: C504060:(R)-(11C)1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide; D000577:Amides; D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; D007546:Isoquinolines; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D019788:Fluorodeoxyglucose F18; D004079:Dihydro-beta-Erythroidine
keywords: 2[18F]-fluoro-A85380; PET; TSPO; [11C]PK11195; cerebral ischemia; α4β2