2. Academic Validation
  3. In vivo imaging of Α7 nicotinic receptors as a novel method to monitor neuroinflammation after cerebral ischemia

In vivo imaging of Α7 nicotinic receptors as a novel method to monitor neuroinflammation after cerebral ischemia

  • Glia. 2018 Aug;66(8):1611-1624. doi: 10.1002/glia.23326.
Lorena Colás 1,  Maria Domercq 2,  Pedro Ramos-Cabrer 3 4,  Ana Palma 2,  Vanessa Gómez-Vallejo 5,  Daniel Padro 3,  Sandra Plaza-García 3,  Krishna R Pulagam 5,  Makoto Higuchi 6,  Carlos Matute 2,  Jordi Llop 5,  Abraham Martín 1
Affiliations

Affiliations

  • 1 Experimental Molecular Imaging, Molecular Imaging Unit, CIC biomaGUNE, P° Miramon 182, San Sebastian, Spain.
  • 2 Department of Neurosciences, University of the Basque Country, Barrio Sarriena s/n, 48940 Leioa, Spain, Achucarro Basque Center for Neuroscience-UPV/EHU, 48170 Zamudio, Spain and Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Leioa, 48940, Spain.
  • 3 Magnetic Resonance Imaging, Molecular Imaging Unit, CIC biomaGUNE, P° Miramon 182, San Sebastian, Spain.
  • 4 Ikerbasque, Basque Foundation for Science, Bilbao, Spain.
  • 5 Radiochemistry and Nuclear Imaging, Molecular Imaging Unit, CIC biomaGUNE, P° Miramon 182, San Sebastian, Spain.
  • 6 National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
PMID: 29528142 DOI: 10.1002/glia.23326
Abstract

In vivo positron emission tomography (PET) imaging of nicotinic acetylcholine receptors (nAChRs) is a promising tool for the imaging evaluation of neurologic and neurodegenerative diseases. However, the role of α7 nAChRs after brain diseases such as cerebral ischemia and its involvement in inflammatory reaction is still largely unknown. In vivo and ex vivo evaluation of α7 nAChRs expression after transient middle cerebral artery occlusion (MCAO) was carried out using PET imaging with [11 C]NS14492 and immunohistochemistry (IHC). Pharmacological activation of α7 receptors was evaluated with magnetic resonance imaging (MRI), [18 F]DPA-714 PET, IHC, real time polymerase chain reaction (qPCR) and neurofunctional studies. In the ischemic territory, [11 C]NS14492 signal and IHC showed an expression increase of α7 receptors in microglia and astrocytes after cerebral ischemia. The role played by α7 receptors on neuroinflammation was supported by the decrease of [18 F]DPA-714 binding in ischemic rats treated with the α7 agonist PHA 568487 at day 7 after MCAO. Moreover, compared with non-treated MCAO rats, PHA-treated ischemic rats showed a significant reduction of the cerebral infarct volumes and an improvement of the neurologic outcome. PHA treatment significantly reduced the expression of leukocyte infiltration molecules in MCAO rats and in endothelial cells after in vitro ischemia. Despite that, the activation of α7 nAChR had no influence to the blood brain barrier (BBB) permeability measured by MRI. Taken together, these results suggest that the nicotinic α7 nAChRs play a key role in the inflammatory reaction and the leukocyte recruitment following cerebral ischemia in rats.

Keywords

MRI; PET; [11C]NS14492; [18F]DPA-714; cerebral ischemia; neuroinflammation.

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