Effects of intravenous administration of dipyridamole in a rat model of chronic cerebral ischemia

Purpose of this study, performed on animals, is to verify if dipyridamole improves cognitive functions in a model of chronic cerebral ischemia in the rat obtained by occlusion of the two carotides (2VO). Such an animal model may mimic, although with some limitation, a situation of chronic hypoperfusion in humans that may be present in aging and neurodegenerative diseases. Dipyridamole (Persantin, Boehringer Ingelheim, 5mg/ml) or vehicle were administered (10 μl/h for 7 days) into the jugular vein by a mini-osmotic pump. 15 rats for group (sham-operated, vehicle-treated and dypiridamole-treated) were tested. The body weight of dipyridamole-treated rats was not different from that of sham-operated rats while it decreased in vehicle-treated rats. In vehicle- and dipyridamole-treated rats, the neurological deficit score decreased 60 and 90 days after 2VO. Spatial working memory evaluated by Y maze test in vehicle-treated rats showed alternation impairment at 60 days and 90 days after 2VO. Dipyridamole-treated rats showed alternation impairment at 60 days after 2VO, but no more at 90 days. Non-spatial working memory evaluated by object recognition test was not different among the three animal groups. Histological damage, assessed by fluoroJB (FJB), 90 days after 2VO showed FJB stained cells selectively in white matter areas of the brain (n=6). No damage was found in the gray matter. No differences were found between vehicle-treated (n=6) and dypiridamoletreated animals (n=6). In conclusion, dipyridamole, although it does not significantly ameliorate neurological deficit, significantly restores working memory.