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Monoacylglycerol lipase (MAGL) is a modulator of 2-arachidonoylglycerol (2-AG), which is involved in retrograde inhibition of glutamate release in the endocannabinoid system. In the present study, we used positron emission tomography (PET) to monitor MAGL-positive neurons and neuroinflammation in the brains of ischemic rats. Additionally, we performed PET imaging to evaluate the neuroprotective effects of an MAGL inhibitor in an ischemic injury model. \nMethods: Ischemic-injury rat models were induced by intraluminal right middle \ncerebral artery occlusion (MCAO). PET studies of the brains of the ischemic rats were performed at several experimental time points (pre-occlusion, days 2, 4, and 7 after the MCAO surgery) using [11C]SAR127303 for MAGL and [18F]FEBMP for 18 kDa translocator protein (TSPO, a hall-mark of neuroinflammation). Medication using minocycline (a well-known neuroprotective agent) or KML29 (a potent MAGL inhibitor) was given immediately after the MCAO surgery and then daily over the subsequent three days. \nResults: PET imaging of the ischemic rats using [11C]SAR127303 showed an acute 4decline of radioactive accumulation in the ipsilateral side at two days after MCAO surgery (ratio of the area under the curve between the ipsilateral and contralateral sides: 0.49 ± 0.04 in the cortex and 0.73 ± 0.02 in the striatum). PET imaging with [18F]FEBMP, however, showed a moderate increase in accumulation of radioactivity in the ipsilateral hemisphere on day 2 (1.36 ± 0.11), and further increases on day 4 (1.72 ± 0.15) and day 7 (1.99 ± 0.06). 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  1. 原著論文

Neuroprotective effects of minocycline and KML29, a potent inhibitor of monoacylglycerol lipase, in an experimental stroke model: a small-animal positron emission tomography study

https://repo.qst.go.jp/records/85189
https://repo.qst.go.jp/records/85189
91213d40-4f9f-4b43-8a20-a29bf6a22d17
Item type 学術雑誌論文 / Journal Article(1)
公開日 2021-09-08
タイトル
タイトル Neuroprotective effects of minocycline and KML29, a potent inhibitor of monoacylglycerol lipase, in an experimental stroke model: a small-animal positron emission tomography study
言語
言語 eng
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_6501
資源タイプ journal article
アクセス権
アクセス権 metadata only access
アクセス権URI http://purl.org/coar/access_right/c_14cb
著者 Tomoteru, Yamasaki

× Tomoteru, Yamasaki

WEKO 1063717

Tomoteru, Yamasaki

Search repository
Akiko, Hatori

× Akiko, Hatori

WEKO 1063718

Akiko, Hatori

Search repository
Zhang, Yiding

× Zhang, Yiding

WEKO 1063719

Zhang, Yiding

Search repository
Kurihara, Yusuke

× Kurihara, Yusuke

WEKO 1063720

Kurihara, Yusuke

Search repository
Masanao, Ogawa

× Masanao, Ogawa

WEKO 1063721

Masanao, Ogawa

Search repository
Hidekatsu, Wakizaka

× Hidekatsu, Wakizaka

WEKO 1063722

Hidekatsu, Wakizaka

Search repository
Rong, Jian

× Rong, Jian

WEKO 1063723

Rong, Jian

Search repository
Lu, Wang

× Lu, Wang

WEKO 1063724

Lu, Wang

Search repository
Liang, Huan

× Liang, Huan

WEKO 1063725

Liang, Huan

Search repository
Zhang, Ming-Rong

× Zhang, Ming-Rong

WEKO 1063726

Zhang, Ming-Rong

Search repository
Tomoteru, Yamasaki

× Tomoteru, Yamasaki

WEKO 1063727

en Tomoteru, Yamasaki

Search repository
Akiko, Hatori

× Akiko, Hatori

WEKO 1063728

en Akiko, Hatori

Search repository
Zhang, Yiding

× Zhang, Yiding

WEKO 1063729

en Zhang, Yiding

Search repository
Kurihara, Yusuke

× Kurihara, Yusuke

WEKO 1063730

en Kurihara, Yusuke

Search repository
Masanao, Ogawa

× Masanao, Ogawa

WEKO 1063731

en Masanao, Ogawa

Search repository
Hidekatsu, Wakizaka

× Hidekatsu, Wakizaka

WEKO 1063732

en Hidekatsu, Wakizaka

Search repository
Lu, Wang

× Lu, Wang

WEKO 1063733

en Lu, Wang

Search repository
Liang, Huan

× Liang, Huan

WEKO 1063734

en Liang, Huan

Search repository
Zhang, Ming-Rong

× Zhang, Ming-Rong

WEKO 1063735

en Zhang, Ming-Rong

Search repository
抄録
内容記述タイプ Abstract
内容記述 Hypoxia caused by ischemia induces acidosis and neuroexcitotoxicity, resulting in neuronal death in the central nervous system (CNS). Monoacylglycerol lipase (MAGL) is a modulator of 2-arachidonoylglycerol (2-AG), which is involved in retrograde inhibition of glutamate release in the endocannabinoid system. In the present study, we used positron emission tomography (PET) to monitor MAGL-positive neurons and neuroinflammation in the brains of ischemic rats. Additionally, we performed PET imaging to evaluate the neuroprotective effects of an MAGL inhibitor in an ischemic injury model.
Methods: Ischemic-injury rat models were induced by intraluminal right middle
cerebral artery occlusion (MCAO). PET studies of the brains of the ischemic rats were performed at several experimental time points (pre-occlusion, days 2, 4, and 7 after the MCAO surgery) using [11C]SAR127303 for MAGL and [18F]FEBMP for 18 kDa translocator protein (TSPO, a hall-mark of neuroinflammation). Medication using minocycline (a well-known neuroprotective agent) or KML29 (a potent MAGL inhibitor) was given immediately after the MCAO surgery and then daily over the subsequent three days.
Results: PET imaging of the ischemic rats using [11C]SAR127303 showed an acute 4decline of radioactive accumulation in the ipsilateral side at two days after MCAO surgery (ratio of the area under the curve between the ipsilateral and contralateral sides: 0.49 ± 0.04 in the cortex and 0.73 ± 0.02 in the striatum). PET imaging with [18F]FEBMP, however, showed a moderate increase in accumulation of radioactivity in the ipsilateral hemisphere on day 2 (1.36 ± 0.11), and further increases on day 4 (1.72 ± 0.15) and day 7 (1.99 ± 0.06). Treatment with minocycline or KML29 eased the decline in radioactive accumulation of [11C]SAR127303 for MAGL (minocycline-treated group:
0.82 ± 0.06 in the cortex and 0.81 ± 0.05 in the striatum; KML29-treated group: 0.72 ± 0.07 in the cortex and 0.88 ± 0.04 in the striatum) and increased uptake of [18F]FEBMP for TSPO (minocycline-treated group: 1.52 ± 0.21 in the cortex and 1.56 ± 0.11 in the striatum; KML29-treated group: 1.63 ± 0.09 in the cortex and 1.50 ± 0.17 in the striatum). In MCAO rats, minocycline treatment showed a neuroprotective effect in the sensorimotor cortex suffering from severe hypoxic injury, whereas KML29 treatment saved neurons in the striatum, including bundles of myelinated axons.
Conclusions: PET imaging allowed visualization of the different neuroprotective
effects of minocycline and KML29, and indicated that combination pharmacotherapy using these drugs may be an effective therapy in acute ischemia.
書誌情報 Theranostics

巻 11, 号 19, p. 9492-9502, 発行日 2021-09
出版者
出版者 IVYSPRING INTERNATIONAL PUBLISHER
ISSN
収録物識別子タイプ ISSN
収録物識別子 1838-7640
DOI
識別子タイプ DOI
関連識別子 10.7150/thno.64320
関連サイト
識別子タイプ URI
関連識別子 https://www.thno.org/v11p9492.htm
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