In vivo multimodal imaging of adenosine A1 receptors in neuroinflammation after experimental stroke

Ana Joya, María Ardaya, Alejandro Montilla, Maider Garbizu, Sandra Plaza-García, Vanessa Gómez-Vallejo, Daniel Padro, Juan José Gutiérrez, Xabier Rios, Pedro Ramos-Cabrer, Unai Cossío, Krishna R. Pulagam, Makoto Higuchi, María Domercq, Fabio Cavaliere, Carlos Matute, Jordi Llop, Abraham Martín

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Adenosine A1 receptors (A1ARs) are promising imaging biomarkers and targets for the treatment of stroke. Nevertheless, the role of A1ARs on ischemic damage and its subsequent neuroinflammatory response has been scarcely explored so far. Methods: In this study, the expression of A1ARs after transient middle cerebral artery occlusion (MCAO) was evaluated by positron emission tomography (PET) with [18F]CPFPX and immunohistochemistry (IHC). In addition, the role of A1ARs on stroke inflammation using pharmacological modulation was assessed with magnetic resonance imaging (MRI), PET imaging with [18F]DPA-714 (TSPO) and [18F]FLT (cellular proliferation), as well as IHC and neurofunctional studies. Results: In the ischemic territory, [18F]CPFPX signal and IHC showed the overexpression of A1ARs in microglia and infiltrated leukocytes after cerebral ischemia. Ischemic rats treated with the A1AR agonist ENBA showed a significant decrease in both [18F]DPA-714 and [18F]FLT signal intensities at day 7 after cerebral ischemia, a feature that was confirmed by IHC results. Besides, the activation of A1ARs promoted the reduction of the brain lesion, as measured with T2W-MRI, and the improvement of neurological outcome including motor, sensory and reflex responses. These results show for the first time the in vivo PET imaging of A1ARs expression after cerebral ischemia in rats and the application of [18F]FLT to evaluate glial proliferation in response to treatment. Conclusion: Notably, these data provide evidence for A1ARs playing a key role in the control of both the activation of resident glia and the de novo proliferation of microglia and macrophages after experimental stroke in rats.

Original languageEnglish
Pages (from-to)410-425
Number of pages16
JournalTheranostics
Volume11
Issue number1
DOIs
Publication statusPublished - 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

Fingerprint

Dive into the research topics of 'In vivo multimodal imaging of adenosine A1 receptors in neuroinflammation after experimental stroke'. Together they form a unique fingerprint.

Cite this