In vivo PET imaging of the α4β2 nicotinic acetylcholine receptor as a marker for brain inflammation after cerebral ischemia

Abraham Martín, Boguslaw Szczupak, Vanessa Gómez-Vallejo, Maria Domercq, Ainhoa Cano, Daniel Padro, Clara Muñoz, Makoto Higuchi, Carlos Matute, Jordi Llop

研究成果: ジャーナルへの寄稿学術論文査読

41 被引用数 (Scopus)

抄録

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[18F]-fluoro-A85380 and [11C]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[18F]-fluoro-A85380 and [11C]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 [11C]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.

本文言語英語
ページ(範囲)5998-6009
ページ数12
ジャーナルJournal of Neuroscience
35
15
DOI
出版ステータス出版済み - 15-04-2015
外部発表はい

All Science Journal Classification (ASJC) codes

  • 医学一般

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