We investigated the effect of
TTC-909, a
drug preparation of the stable
prostaglandin I(2) analogue
clinprost (
isocarbacyclin methylester; methyl 5-[(1S,5S,6R,7R)-7-hydroxy-6-[(E)-(S)-3-hydroxy-1-octenyl] bicyclo[3.3.0]oct-2-en-3-yl]
pentanoate) incorporated into
lipid microspheres, on
cerebral infarction 7 days after permanent occlusion of the middle cerebral artery (MCA) in
stroke prone spontaneously hypertensive rats (SHRSP). Under the
anesthesia, the MCA was permanently occluded above the rhinal fissure. In schedule 1, vehicle or
TTC-909 was injected i.v. once daily over 7 days starting immediately after MCA occlusion. In schedule 2, vehicle or
TTC-909 was infused for 3 h starting immediately after MCA occlusion. In schedule 3, vehicle or
TTC-909 was infused for 3 h starting immediately after MCA occlusion followed by bolus injection once daily over 6 days. Seven days later, the
infarct volume was estimated following
hematoxylin and
eosin staining.
Cerebral infarction produced by permanent occlusion of MCA was limited to the cerebral cortex. While this volume was reduced significantly in case of schedule 3, the
infarct volume was not reduced significantly in schedules 1 and 2.
Ozagrel, a
thromboxane A(2)
synthetase inhibitor, had no effect on the
infarct volume in schedule 3. These results suggest that
cerebral infarction can be developed progressively not only during the first few hours but also after a permanent occlusion of MCA in SHRSP.
TTC-909 inhibited
cerebral infarction, maybe by improving cerebral blood flow and by protecting against neuronal damage.