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

¹ Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu, Japan
² Central Research Laboratory, Hamamatsu Photonics K.K., Shizuoka, Japan
³ Pharmaceutical Research Laboratories, Toray Industries, Inc., Kanagawa, Japan

View larger version (9K): [in a new window]   FIGURE 1. The experimental procedure.

View larger version (19K): [in a new window]   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.

View larger version (23K): [in a new window]   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.

View larger version (15K): [in a new window]   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.

View larger version (10K): [in a new window]   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.

View larger version (13K): [in a new window]   FIGURE 6. Correlation between >40% decrease in CMRO2, compared with preischemic scan, and amount of brain damage (histologically confirmed) at 4 d after reperfusion.