Abstract | UNLABELLED: METHODS: Via a transorbital approach, cynomolgus monkeys underwent a 3-h occlusion of the right middle cerebral artery (MCA), followed by reperfusion and observation for 4 d. Starting 2 h after the MCA occlusion, TRA-418 was administered at low and high doses (6 animals at each dose). Six control animals received a bolus and infusion of drug vehicle after MCA occlusion. Steady-state (15)O continuous inhalation was used for assessment of local cerebral blood flow, cerebral metabolic rate of oxygen, and oxygen extraction fraction using high-resolution PET. Five consecutive PET scans (before occlusion; 2 h after occlusion; and 2 h, 24 h, and 4 d after reperfusion) were obtained for each monkey. The extent of the cerebral damage due to ischemia was measured histologically at 4 d after reperfusion. RESULTS: Histologic observation 4 d after MCA occlusion showed that cerebral damage was less (P = 0.05) in animals treated with high-dose TRA-418 than in control animals. Although not affecting cerebral blood flow during the experiments, treatment with TRA-418 significantly (P < 0.05) suppressed reduction of the cerebral metabolic rate of oxygen after reperfusion. CONCLUSION: Our observations suggest that TRA-418 has neuroprotective action, as displayed in a primate model of stroke using PET monitoring.
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Authors | Kazuo Umemura, Hideo Tsukada, Takeharu Kakiuchi, Naohiro Yamada, Hirotoshi Matsuura |
Journal | Journal of nuclear medicine : official publication, Society of Nuclear Medicine
(J Nucl Med)
Vol. 46
Issue 11
Pg. 1931-6
(Nov 2005)
ISSN: 0161-5505 [Print] United States |
PMID | 16269609
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Neuroprotective Agents
- Oxazines
- Platelet Aggregation Inhibitors
- TRA418
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Topics |
- Animals
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Humans
- Macaca fascicularis
- Male
- Neuroprotective Agents
(administration & dosage)
- Oxazines
(administration & dosage)
- Platelet Aggregation Inhibitors
(administration & dosage)
- Positron-Emission Tomography
- Stroke
(diagnostic imaging, prevention & control)
- Treatment Outcome
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