TY - JOUR
T1 - Therapeutic effect of α7 nicotinic receptor activation after ischemic stroke in rats
AU - Aguado, Laura
AU - Joya, Ana
AU - Garbizu, Maider
AU - Plaza-García, Sandra
AU - Iglesias, Leyre
AU - Hernández, María Isabel
AU - Ardaya, María
AU - Mocha, Naroa
AU - Gómez-Vallejo, Vanessa
AU - Cossio, Unai
AU - Higuchi, Makoto
AU - Rodríguez-Antigüedad, Alfredo
AU - Freijo, Mari Mar
AU - Domercq, María
AU - Matute, Carlos
AU - Ramos-Cabrer, Pedro
AU - Llop, Jordi
AU - Martín, Abraham
N1 - Publisher Copyright:
© The Author(s) 2023.
PY - 2023/8
Y1 - 2023/8
N2 - Nicotinic acetylcholine α7 receptors (α7 nAChRs) have a well-known modulator effect in neuroinflammation. Yet, the therapeutical effect of α7 nAChRs activation after stroke has been scarcely evaluated to date. The role of α7 nAChRs activation with PHA 568487 on inflammation after brain ischemia was assessed with positron emission tomography (PET) using [18F]DPA-714 and [18F]BR-351 radiotracers after transient middle cerebral artery occlusion (MCAO) in rats. The assessment of brain oedema, blood brain barrier (BBB) disruption and neurofunctional progression after treatment was evaluated with T2 weighted and dynamic contrast-enhanced magnetic resonance imaging (T2 W and DCE-MRI) and neurological evaluation. The activation of α7 nAChRs resulted in a decrease of ischemic lesion, midline displacement and cell neurodegeneration from days 3 to 7 after ischemia. Besides, the treatment with PHA 568487 improved the neurofunctional outcome. Treated ischemic rats showed a significant [18F]DPA-714-PET uptake reduction at day 7 together with a decrease of activated microglia/infiltrated macrophages. Likewise, the activation of α7 receptors displayed an increase of [18F]BR-351-PET signal in ischemic cortical regions, which resulted from the overactivation of MMP-2. Finally, the treatment with PHA 568487 showed a protective effect on BBB disruption and blood brain vessel integrity after cerebral ischemia.
AB - Nicotinic acetylcholine α7 receptors (α7 nAChRs) have a well-known modulator effect in neuroinflammation. Yet, the therapeutical effect of α7 nAChRs activation after stroke has been scarcely evaluated to date. The role of α7 nAChRs activation with PHA 568487 on inflammation after brain ischemia was assessed with positron emission tomography (PET) using [18F]DPA-714 and [18F]BR-351 radiotracers after transient middle cerebral artery occlusion (MCAO) in rats. The assessment of brain oedema, blood brain barrier (BBB) disruption and neurofunctional progression after treatment was evaluated with T2 weighted and dynamic contrast-enhanced magnetic resonance imaging (T2 W and DCE-MRI) and neurological evaluation. The activation of α7 nAChRs resulted in a decrease of ischemic lesion, midline displacement and cell neurodegeneration from days 3 to 7 after ischemia. Besides, the treatment with PHA 568487 improved the neurofunctional outcome. Treated ischemic rats showed a significant [18F]DPA-714-PET uptake reduction at day 7 together with a decrease of activated microglia/infiltrated macrophages. Likewise, the activation of α7 receptors displayed an increase of [18F]BR-351-PET signal in ischemic cortical regions, which resulted from the overactivation of MMP-2. Finally, the treatment with PHA 568487 showed a protective effect on BBB disruption and blood brain vessel integrity after cerebral ischemia.
KW - Cerebral ischemia
KW - MRI
KW - PET
KW - metalloproteinases
KW - neuroinflammation
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U2 - 10.1177/0271678X231161207
DO - 10.1177/0271678X231161207
M3 - Article
C2 - 36916034
AN - SCOPUS:85150796413
SN - 0271-678X
VL - 43
SP - 1301
EP - 1316
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
IS - 8
ER -