We evaluated the effects of cilostazol, a selective inhibitor of cyclic adenosine monophosphate phosphodiesterase, on the pial vessels of adult cats subjected to endothelial damage followed by middle cerebral artery occlusion. Six cats were treated with cilostazol and four with 30% JVVV-dimethylfonnamide in 70% saline (solvent). The brain surface was irradiated with ultraviolet rays through a cranial window for 3 minutes to selectively damage the endothelium of the pial vessels in both groups. Beginning 32 minutes after termination of the irradiation, the middle cerebral artery was occluded for 30 minutes. Thirty minutes before occlusion, intravenous infusion of 30 /ig/kg/min cilostazol or 0.1 ml/kg/min solvent was begun and continued until the end of the study. Before occlusion, the infusion of cilostazol induced a significant (p<0.05) dilatation while the infusion of solvent produced no significant changes in the diameter of the pial arteries. The pial veins of solvent-treated cats showed significant (p<0.05) constriction during occlusion, whereas cilostazol-treated cats exhibited only mild constriction of the pial veins. The formation of platelet thrombi after occlusion was significantly (p<0.05) inhibited in the pial veins of cilostazol-treated compared with solvent-treated cats. Similarly, the microcirculation of the pial veins was effectively restored after reopening of the middle cerebral artery in cilostazol-treated compared with solvent-treated cats. Our data suggest that cilostazol is an effective antithrombotic agent as well as a potent vasodilator acting on vascular smooth muscle. (Stroke 1989;20:668-673)

The blood flow velocity and diameter of feline pial arteries, ranging in diameter from 20 to 200 microns, were measured simultaneously using a newly developed video camera method under steady-state conditions for all other parameters. There was a linear relationship between blood flow velocity and pial artery diameter (y = 0.340x + 0.309), the correlation coefficient being 0.785 (p less than 0.001). The average values for blood flow velocity in pial arteries less than 50 microns, greater than or equal to 50 but less than 100 microns, greater than or equal to 100 but less than 150 microns, and greater than or equal to 150 microns in diameter were 12.9 +/- 1.3, 24.6 +/- 3.4, 42.1 +/- 4.7, and 59.9 +/- 5.3 mm/s, respectively. Blood flow rate was calculated as a product of the cross-sectional area and the flow velocity. The blood flow rate increased exponentially as the pial artery diameter increased (y = 2.71 X 10(-4) x2.98). The average values for blood flow rate in pial arteries less than 50 microns, greater than or equal to 50 but less than 100 microns, greater than or equal to 100 but less than 150 microns and greater than or equal to 150 microns in diameter were 12.8 +/- 1.5, 122.1 +/- 24.8, 510.2 +/- 74.8, and 1524.2 +/- 174.4 10(-3) mm3/s, respectively. Hemorheological parameters such as the wall shear rate and Reynolds' number were also calculated. The data obtained provide a useful basis for further investigations in the field of cerebral circulation.

Calcium ion can enter ischemic neurons through both receptor-operated and voltage-sensitive Ca2+ channels. To attenuate this Ca2+ entry and Ca2(+)-induced neuronal injury, we tried a combined treatment with the noncompetitive N-methyl-D-aspartate (NMDA) antagonist, MK-801, and the dihydropyridine calcium antagonist, nimodipine, in a cat middle cerebral artery occlusion (1 hour) and reperfusion (3 hours) model. We measured changes in cytosolic free calcium, nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide redox state, and blood flow in the cat cortex using a newly developed fluorometric technique with indo-1, a fluorescent intracellular Ca2+ indicator. The combined treatment, starting 5 minutes into ischemia, was effective in reducing both Ca2+ entry and histologic damage and in enhancing recovery of the electroencephalogram following reperfusion. MK-801 alone was also effective, but to a lesser extent. These data suggest that the dual blockade of Ca2+ entry using MK-801 and nimodipine may be a useful tool for protection against ischemic brain damage.

Our data did not reach statistical significance regarding the efficacy of YKS against BPSD; however, YKS improves some symptoms including "agitation/aggression" and "hallucinations" with low frequencies of adverse events. Geriatr Gerontol Int 2017; 17: 211-218.

To clarify the mechanism of its effect on ischemic stroke, we investigated the effect of nimodipine, a dihydropyridine calcium antagonist, on changes in cytosolic free calcium, cortical blood flow, and histologic changes following focal cerebral ischemia and reperfusion in 14 cats. Using indo-1, a fluorescent intracellular Ca 2+ indicator, we simultaneously measured changes in the Ca 2+ signal ratio (400 506 nm), reduced nicotinamide adenine dinucleotide fluorescence (464 nm), and reflectance (340 nm) during an ultraviolet excitation (340 nm) directly from the cat cortex in vivo. In six cats treated with vehicle only, the calcium signal ratio increased from 5 minutes after middle cerebral artery occlusion to 30 minutes into reperfusion. The elevation of cytosolic free calcium was significantly attenuated by nimodipine, which was administered by intravenous infusion in eight cats starting 5 minutes after occlusion. Nimodipine had no effect on cortical blood flow during ischemia but induced a hyperperfused state following reperfusion. Nimodipine did not modify changes in the mitochondrial oxidation-reduction state. Nimodipine proved to have beneficial effects on recovery of the electroencephalogram following reperfusion as well as on the extent of focal histologic damage. Our results suggest that nimodipine, when administered during the early stage of focal ischemia, can favorably modify the outcome of stroke by reducing the Ca 2+ entry during both the ischemic and reperfusion periods. (Stroke 1989;20:1531-1537 I n contrast to a relatively good understanding of the hemodynamic and metabolic aspects of stroke, a great deal remains to be clarified concerning the biochemical mechanisms underlying ischemia-induced cellular injury. In the past decade several mechanisms have been postulated to be involved in the production of ischemic and reperfusion injury: acidosis, ], can be assessed in vivo along with changes in nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide (NAD/NADH) oxidation-reduction (redox) state and hemodynamics.