Neuroprotection by a Central Nervous System–Type Prostacyclin Receptor Ligand Demonstrated in Monkeys Subjected to Middle Cerebral Artery Occlusion and Reperfusion
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- Yilong Cui
- From Molecular Imaging Research Program (Y.C., Y.K., C.Y., H.O., Y.W., M.S., Y.W.), Frontier Research System, Institute of Physical and Chemical Research (RIKEN), Wako, Saitama, Japan; Department of Physiology (Y.C., Y.K., Y.W., Y.W.), Osaka City University Graduate School of Medicine, Osaka, Japan; Hamamatsu Pharma Research, Inc (H.T.), Hamamatsu, Shizuoka, Japan; Central Research Laboratory (T.K., H.O., H.T.), Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan; Department of Biomolecular Science...
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- Hiroyuki Takamatsu
- From Molecular Imaging Research Program (Y.C., Y.K., C.Y., H.O., Y.W., M.S., Y.W.), Frontier Research System, Institute of Physical and Chemical Research (RIKEN), Wako, Saitama, Japan; Department of Physiology (Y.C., Y.K., Y.W., Y.W.), Osaka City University Graduate School of Medicine, Osaka, Japan; Hamamatsu Pharma Research, Inc (H.T.), Hamamatsu, Shizuoka, Japan; Central Research Laboratory (T.K., H.O., H.T.), Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan; Department of Biomolecular Science...
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- Takeharu Kakiuchi
- From Molecular Imaging Research Program (Y.C., Y.K., C.Y., H.O., Y.W., M.S., Y.W.), Frontier Research System, Institute of Physical and Chemical Research (RIKEN), Wako, Saitama, Japan; Department of Physiology (Y.C., Y.K., Y.W., Y.W.), Osaka City University Graduate School of Medicine, Osaka, Japan; Hamamatsu Pharma Research, Inc (H.T.), Hamamatsu, Shizuoka, Japan; Central Research Laboratory (T.K., H.O., H.T.), Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan; Department of Biomolecular Science...
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- Hiroyuki Ohba
- From Molecular Imaging Research Program (Y.C., Y.K., C.Y., H.O., Y.W., M.S., Y.W.), Frontier Research System, Institute of Physical and Chemical Research (RIKEN), Wako, Saitama, Japan; Department of Physiology (Y.C., Y.K., Y.W., Y.W.), Osaka City University Graduate School of Medicine, Osaka, Japan; Hamamatsu Pharma Research, Inc (H.T.), Hamamatsu, Shizuoka, Japan; Central Research Laboratory (T.K., H.O., H.T.), Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan; Department of Biomolecular Science...
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- Yosky Kataoka
- From Molecular Imaging Research Program (Y.C., Y.K., C.Y., H.O., Y.W., M.S., Y.W.), Frontier Research System, Institute of Physical and Chemical Research (RIKEN), Wako, Saitama, Japan; Department of Physiology (Y.C., Y.K., Y.W., Y.W.), Osaka City University Graduate School of Medicine, Osaka, Japan; Hamamatsu Pharma Research, Inc (H.T.), Hamamatsu, Shizuoka, Japan; Central Research Laboratory (T.K., H.O., H.T.), Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan; Department of Biomolecular Science...
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- Chihiro Yokoyama
- From Molecular Imaging Research Program (Y.C., Y.K., C.Y., H.O., Y.W., M.S., Y.W.), Frontier Research System, Institute of Physical and Chemical Research (RIKEN), Wako, Saitama, Japan; Department of Physiology (Y.C., Y.K., Y.W., Y.W.), Osaka City University Graduate School of Medicine, Osaka, Japan; Hamamatsu Pharma Research, Inc (H.T.), Hamamatsu, Shizuoka, Japan; Central Research Laboratory (T.K., H.O., H.T.), Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan; Department of Biomolecular Science...
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- Hirotaka Onoe
- From Molecular Imaging Research Program (Y.C., Y.K., C.Y., H.O., Y.W., M.S., Y.W.), Frontier Research System, Institute of Physical and Chemical Research (RIKEN), Wako, Saitama, Japan; Department of Physiology (Y.C., Y.K., Y.W., Y.W.), Osaka City University Graduate School of Medicine, Osaka, Japan; Hamamatsu Pharma Research, Inc (H.T.), Hamamatsu, Shizuoka, Japan; Central Research Laboratory (T.K., H.O., H.T.), Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan; Department of Biomolecular Science...
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- Yumiko Watanabe
- From Molecular Imaging Research Program (Y.C., Y.K., C.Y., H.O., Y.W., M.S., Y.W.), Frontier Research System, Institute of Physical and Chemical Research (RIKEN), Wako, Saitama, Japan; Department of Physiology (Y.C., Y.K., Y.W., Y.W.), Osaka City University Graduate School of Medicine, Osaka, Japan; Hamamatsu Pharma Research, Inc (H.T.), Hamamatsu, Shizuoka, Japan; Central Research Laboratory (T.K., H.O., H.T.), Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan; Department of Biomolecular Science...
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- Takamitsu Hosoya
- From Molecular Imaging Research Program (Y.C., Y.K., C.Y., H.O., Y.W., M.S., Y.W.), Frontier Research System, Institute of Physical and Chemical Research (RIKEN), Wako, Saitama, Japan; Department of Physiology (Y.C., Y.K., Y.W., Y.W.), Osaka City University Graduate School of Medicine, Osaka, Japan; Hamamatsu Pharma Research, Inc (H.T.), Hamamatsu, Shizuoka, Japan; Central Research Laboratory (T.K., H.O., H.T.), Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan; Department of Biomolecular Science...
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- Masaaki Suzuki
- From Molecular Imaging Research Program (Y.C., Y.K., C.Y., H.O., Y.W., M.S., Y.W.), Frontier Research System, Institute of Physical and Chemical Research (RIKEN), Wako, Saitama, Japan; Department of Physiology (Y.C., Y.K., Y.W., Y.W.), Osaka City University Graduate School of Medicine, Osaka, Japan; Hamamatsu Pharma Research, Inc (H.T.), Hamamatsu, Shizuoka, Japan; Central Research Laboratory (T.K., H.O., H.T.), Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan; Department of Biomolecular Science...
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- Ryoji Noyori
- From Molecular Imaging Research Program (Y.C., Y.K., C.Y., H.O., Y.W., M.S., Y.W.), Frontier Research System, Institute of Physical and Chemical Research (RIKEN), Wako, Saitama, Japan; Department of Physiology (Y.C., Y.K., Y.W., Y.W.), Osaka City University Graduate School of Medicine, Osaka, Japan; Hamamatsu Pharma Research, Inc (H.T.), Hamamatsu, Shizuoka, Japan; Central Research Laboratory (T.K., H.O., H.T.), Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan; Department of Biomolecular Science...
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- Hideo Tsukada
- From Molecular Imaging Research Program (Y.C., Y.K., C.Y., H.O., Y.W., M.S., Y.W.), Frontier Research System, Institute of Physical and Chemical Research (RIKEN), Wako, Saitama, Japan; Department of Physiology (Y.C., Y.K., Y.W., Y.W.), Osaka City University Graduate School of Medicine, Osaka, Japan; Hamamatsu Pharma Research, Inc (H.T.), Hamamatsu, Shizuoka, Japan; Central Research Laboratory (T.K., H.O., H.T.), Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan; Department of Biomolecular Science...
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- Yasuyoshi Watanabe
- From Molecular Imaging Research Program (Y.C., Y.K., C.Y., H.O., Y.W., M.S., Y.W.), Frontier Research System, Institute of Physical and Chemical Research (RIKEN), Wako, Saitama, Japan; Department of Physiology (Y.C., Y.K., Y.W., Y.W.), Osaka City University Graduate School of Medicine, Osaka, Japan; Hamamatsu Pharma Research, Inc (H.T.), Hamamatsu, Shizuoka, Japan; Central Research Laboratory (T.K., H.O., H.T.), Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan; Department of Biomolecular Science...
書誌事項
- タイトル別名
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- A Positron Emission Tomography Study
説明
<jats:p> <jats:bold> <jats:italic>Background and Purpose—</jats:italic> </jats:bold> Recently, we found that a novel subtype of prostacyclin (PGI <jats:sub>2</jats:sub> ) receptor clearly distinct from the peripheral subtype in terms of ligand specificity is expressed in the central nervous system (CNS). (15R)-16- <jats:italic>m</jats:italic> -tolyl-17,18,19,20-tetranorisocarbacyclin (15R-TIC) was synthesized and demonstrated to be a specific ligand for this CNS-type PGI <jats:sub>2</jats:sub> receptor. Previously, we demonstrated 15R-TIC to be neuroprotective in vivo during transient forebrain ischemia in gerbils and permanent middle cerebral artery occlusion (MCAO) in rats. Furthermore, this compound was shown to exert an anti-apoptotic effect on primary cultured hippocampal neurons, indicating its neuroprotective effect against ischemic insults occurs via direct action on CNS-type PGI <jats:sub>2</jats:sub> receptor. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods—</jats:italic> </jats:bold> Local cerebral hemodynamics and oxygen metabolism were measured simultaneously by using positron emission tomography with the <jats:sup>15</jats:sup> O steady-state method, before and up to 18 hours after 3-hour transient MCAO reperfusion in cynomolgus monkeys. Methyl ester of 15R-TIC (50 μg/kg, n=4) or its vehicle (10% Intralipos, n=4) was injected intravenously within 5 minutes after onset of MCAO and continuously infused for 5 hours (50 μg/kg per hour). </jats:p> <jats:p> <jats:bold> <jats:italic>Results—</jats:italic> </jats:bold> Neuropathology showed that 15R-TIC significantly reduced cortical damage after 3-hour MCAO. Positron emission tomography results showed 15R-TIC significantly reduced the volume of “infarct” region of interest and attenuated the decrease in cerebral metabolic rate of oxygen and oxygen extraction fraction, and these protective effects were not attributable to improvement of cerebral circulation. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> These results suggest that 15R-TIC has a potent neuroprotective effect against focal cerebral ischemia in a monkey MCAO via its direct action on CNS-type PGI <jats:sub>2</jats:sub> receptors. </jats:p>
収録刊行物
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- Stroke
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Stroke 37 (11), 2830-2836, 2006-11
Ovid Technologies (Wolters Kluwer Health)
