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OtherBasic Science Investigations

PET Study of the Neuroprotective Effect of TRA-418, an Antiplatelet Agent, in a Monkey Model of Stroke

Kazuo Umemura, Hideo Tsukada, Takeharu Kakiuchi, Naohiro Yamada and Hirotoshi Matsuura
Journal of Nuclear Medicine November 2005, 46 (11) 1931-1936;
Kazuo Umemura
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Hideo Tsukada
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Takeharu Kakiuchi
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Naohiro Yamada
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Hirotoshi Matsuura
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  • FIGURE 1.
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    FIGURE 1.

    The experimental procedure.

  • FIGURE 2.
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    FIGURE 2.

    (A) Effect of TRA-418 on extent of cerebral damage. TRA-418 at high dose reduced damaged area in coronal slices (18 mm anterior to interaural) (P = 0.05). Data are presented as mean ± SE (n = 6). (B) Photographs of typical coronal slices (18 and 24 mm anterior to interaural) in animals treated with vehicle or high-dose TRA-418.

  • FIGURE 3.
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    FIGURE 3.

    (A) PET images of typical CBF before and during ischemia and at 2 and 24 h after reperfusion in animals treated with vehicle or high-dose TRA-418. (B) Effect of TRA-418 on CBF. No significant differences were found between animals treated with vehicle and animals treated with either TRA-418 dose. CBF reduction was calculated by dividing each PET image of cerebrum by its baseline image and determining the areas of −20% to 20%, 21% to 40%, and >40% change in CBF. Areas were calculated as percentage area divided by total hemispheric area of nonischemic side.

  • FIGURE 4.
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    FIGURE 4.

    (A) PET images of typical CMRO2 at 24 h and 4 d after reperfusion in animals treated with vehicle or high-dose TRA-418. (B) Effect of TRA-418 on CMRO2 reduction, where CMRO2 decreased by more than 40% compared with preischemic scan. High-dose TRA-418 significantly suppressed (P < 0.05) CMRO2 reduction at 24 h after reperfusion. Data are presented as mean ± SE. Areas were calculated as percentage area divided by total hemispheric area of nonischemic side.

  • FIGURE 5.
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    FIGURE 5.

    Effect of TRA-418 on OEF reduction, where OEF decreased by more than 40% compared with preischemic scan. High-dose TRA-418 significantly (P < 0.05) inhibited OEF reduction. Data are presented as mean ± SE.

  • FIGURE 6.
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    FIGURE 6.

    Correlation between >40% decrease in CMRO2, compared with preischemic scan, and amount of brain damage (histologically confirmed) at 4 d after reperfusion.

Tables

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    TABLE 1

    Physiologic Parameters for Glucose and Partial Pressures of CO2 and O2

    OcclusionAdministrationDosenGlucose (mg/dL)Partial pressure of CO2 (mm Hg)Partial pressure of O2 (mm Hg)
    Before MCA occlusionVehicle660.0 ± 7.533.2 ± 0.6156.6 ± 7.1
    TRA-418Low663.1 ± 8.732.8 ± 1.0167.8 ± 10.6
    High664.4 ± 8.034.0 ± 1.1162.3 ± 9.3
    2 h after MCA occlusionVehicle669.4 ± 9.632.8 ± 0.6151.4 ± 4.5
    TRA-418Low673.0 ± 10.133.8 ± 0.5160.3 ± 8.7
    High676.9 ± 11.133.5 ± 1.0144.4 ± 7.7
    2 h after reperfusionVehicle680.6 ± 13.032.4 ± 0.6148.4 ± 5.2
    TRA-418Low688.3 ± 14.433.4 ± 0.4155.8 ± 11.3
    High692.3 ± 16.131.8 ± 0.9145.7 ± 13.2
    24 h after reperfusionVehicle660.4 ± 7.732.9 ± 1.7159.3 ± 12.5
    TRA-418Low654.3 ± 5.733.9 ± 1.5147.9 ± 12.3
    High659.4 ± 9.934.4 ± 0.6145.6 ± 11.2
    4 d after reperfusionVehicle668.7 ± 8.332.4 ± 0.6171.3 ± 4.2
    TRA-418Low691.6 ± 16.133.8 ± 0.9158.9 ± 7.3
    High673.8 ± 9.733.2 ± 1.0156.8 ± 5.2
    • Data are mean ± SE.

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    TABLE 2

    Physiologic Parameters for Mean Arterial Blood Pressure, Heart Rate, and Rectal Temperature

    OcclusionAdministrationDosenMean arterial blood pressure (mm Hg)Heart rate (bpm)Rectal temperature (°C)
    Before MCA occlusionVehicle5104 ± 3143 ± 1036.7 ± 0.3
    TRA-418Low6103 ± 5146 ± 736.7 ± 0.4
    High6100 ± 4150 ± 1336.5 ± 0.3
    1 h after MCA occlusionVehicle5108 ± 3144 ± 1136.6 ± 0.1
    TRA-418Low6100 ± 10154 ± 936.7 ± 0.2
    High6100 ± 5160 ± 736.7 ± 0.4
    Just after reperfusionVehicle591 ± 14146 ± 1237.2 ± 0.3
    TRA-418Low697 ± 10160 ± 1036.7 ± 0.3
    High689 ± 2151 ± 1237.1 ± 0.3
    2 h after reperfusionVehicle5103 ± 4159 ± 1337.2 ± 0.2
    TRA-418Low6105 ± 6153 ± 836.7 ± 0.5
    High695 ± 4157 ± 837.3 ± 0.3
    24 h after reperfusionVehicle588 ± 6145 ± 1237.2 ± 0.4
    TRA-418Low678 ± 4152 ± 935.6 ± 1.2
    High681 ± 3172 ± 437.1 ± 0.3
    4 d after reperfusionVehicle598 ± 4169 ± 836.8 ± 0.0
    TRA-418Low687 ± 4175 ± 1236.7 ± 0.2
    High685 ± 3170 ± 535.8 ± 1.1
    • Data are mean ± SE.

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Journal of Nuclear Medicine: 46 (11)
Journal of Nuclear Medicine
Vol. 46, Issue 11
November 1, 2005
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PET Study of the Neuroprotective Effect of TRA-418, an Antiplatelet Agent, in a Monkey Model of Stroke
Kazuo Umemura, Hideo Tsukada, Takeharu Kakiuchi, Naohiro Yamada, Hirotoshi Matsuura
Journal of Nuclear Medicine Nov 2005, 46 (11) 1931-1936;

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PET Study of the Neuroprotective Effect of TRA-418, an Antiplatelet Agent, in a Monkey Model of Stroke
Kazuo Umemura, Hideo Tsukada, Takeharu Kakiuchi, Naohiro Yamada, Hirotoshi Matsuura
Journal of Nuclear Medicine Nov 2005, 46 (11) 1931-1936;
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